Cancer

ENZYMATICALLY ACTIVATABLE PEPTIDE-REDOX MODULATOR CONJUGATES AND USE THEREOF (Fri, 13 Jul 2018)
Disclosed are peptides capable of enzymatically-induced self-assembly to which is conjugated a redox modulator. These peptides are enzymatically responsive hydrogelators, and they can be used to form pericellular hydrogels/nanofibrils upon exposure to target cells that secrete or express a surface bound ectoenzyme having hydrolase activity suitable to induce peptide gelation. These materials, and compositions containing the same, can be used for inhibiting cancer cell migration, inhibiting cancer cell survival, and/or inhibiting cancer cell growth.
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COMBINATION THERAPY FOR THE TREATMENT OF CANCER (Fri, 13 Jul 2018)
Compositions, combinations and methods comprising the administration of a CDK4/6 inhibitor of Formula D with a selective estrogen receptor downregulator of Formula A, B or C that are advantageous for the treatment of abnormal cellular proliferation, including a cancer or a tumor.
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SMALL MOLECULE INHIBITORS OF NEUTRAL SPHINGOMYELINASE 2 (nSMase2) FOR THE TREATMENT OF NEURODEGENERATIVE DISEASES (Fri, 13 Jul 2018)
Small molecule inhibitors of neutral sphingomyelinase 2 (nSMase2) and their use for treating neurodegenerative diseases, such as, neurodegenerative diseases associated with high levels of ceramide, including, but not limited to Alzheimer's disease (AD), HIV-associated neurocognitive disorder (HAND), multiple sclerosis (MS), and amyotrophic lateral sclerosis (ALS), and, in other aspects, for treating cancer, are provided.
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POLYMORPHIC FORMS OF RAD1901-2HCL (Fri, 13 Jul 2018)
Various polymorphic forms of RAD1901-2HCl, including three crystalline and amorphous forms, are prepared and characterized. Uses of the various polymorphic forms of RAD1901-2HCl for cancer treatment are also disclosed.
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SELECTIVE HISTONE DEACETYLASE INHIBITORS FOR THE TREATMENT OF HUMAN DISEASE (Fri, 13 Jul 2018)
Selective HDAC inhibitors, and pharmaceutical compositions that include the same, are described herein for the treatment of cancer, immunological diseases, inflammatory diseases, and neurological diseases.
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DIPHOSPHINO METALLIC COMPLEXES, METHODS OF MAKING AND USING (Fri, 06 Jul 2018)
Diphosphino metallic complexes, methods of making and using are described. The complexes display cytotoxicity against a panel of cancer cell lines, and optionally display luminescent properties. They have improved solubility and are stable against hydrolysis in physiologically reducing conditions. In some aspects, the complexes are iridium (III) diphosphine complexes. The compounds and pharmaceutical compositions thereof can be administered to a subject in need thereof to treat a host of diseases and disorders including but not limited to, proliferative disorders such as cancer.
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OXAZOLE DERIVATIVES FOR USE IN THE TREATMENT OF CANCER (Fri, 06 Jul 2018)
A first aspect of the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt or ester thereof, • B is a saturated or partially unsaturated monocyclic or bicyclic, heterocyclic group optionally substituted by one or more R 10 groups; * X is selected from SO2, CO2, CO, CONR11 and (CR12 R13 ) p. Said compounds are capable of inhibiting PAICS and are useful in the treatment of proliferative disorders. Further aspects relate to pharmaceutical compositions, therapeutic uses and process for preparing compounds of formula (I).
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OXAZOLE DERIVATIVES FOR USE IN THE TREATMENT OF CANCER (Fri, 06 Jul 2018)
A first aspect of the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt or ester thereof, wherein: • B is an aryl or heteroaryl group optionally substituted by one or more R10 groups; and * X is selected from 0, (CR11 R12 ) p and (CR11 R12 ) p CO. Said compounds are capable of inhibiting PAICS and are useful in the treatment of proliferative disorders. Further aspects relate to pharmaceutical compositions, therapeutic uses and process for preparing compounds of formula (I).
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TEMOZOLOMIDE PROCESS (Fri, 06 Jul 2018)
The present invention relates to improved process for the preparation of Temozolomide Formula I. Said Temozolomide (I) is useful in the treatment of cancer.
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A NANOCOMPLEX (Fri, 06 Jul 2018)
There is provided a nanocomplex having a core-shell structure. The shell of the nanocomplex comprises a functionalized hyaluronic acid while the core of the nanocomplex comprises a flavonoid encapsulating a metal-containing compound. Preferrably, the flavonoid is epigallocatechin gallate (EGCG) and the hyaluronic acid is thiol-functionalized and subsequently conjugated to the flavonoid. There is also provided a method of forming the nanocomplex, a pharmaceutical composition comprising the nanocomplex, medical uses of the nanocomplex and a method of treating a patient, preferably with cancer using the nanocomplex.
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GLUT4 SELECTIVE INHIBITORS FOR CANCER THERAPY (Fri, 06 Jul 2018)
This disclosure relates to GLUT 4 inhibitors and uses as chemotherapy agents. In certain embodiments, this disclosure relates to methods of treating or preventing cancer comprising administering an effective amount of a GLUT 4 inhibitor disclosed herein to a subject in need thereof. In certain embodiments, the GLUT 4 inhibitor has Formula (I), prodrugs, derivatives, or salts thereof wherein the substituents are reported herein. In certain embodiments, the GLUT 4 inhibitor is N-(3-(4-fluorophenethoxy)benzyl)-2-(4-methoxyphenyl)- N-(pyridin-4-ylmethyl)acetamide or salts thereof.
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HETEROCYCLIC INTEGRIN AGONISTS (Fri, 06 Jul 2018)
The present invention provides polycyclic oxothioxoimidazolidines, dioxoimidazolines, oxothioxooxazolidines, dioxooxazolidines, and related compounds, which are useful as integrin agonists. Methods for the treatment of integrin-mediated diseases such as cancer are also described.
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ANTI-LAIR1 ANTIBODIES AND THEIR USES (Fri, 06 Jul 2018)
The present disclosure is directed to antibodies binding to LAIR 1 and their treating cancer, inflammation, immune-related diseases or transplantation.
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QUINAZOLINE INHIBITORS OF ACTIVATING MUTANT FORMS OF EPIDERMAL GROWTH FACTOR RECEPTOR (Thu, 05 Jul 2018)
The invention relates to compounds of formula (I), or a pharmaceutically acceptable salt thereof: Formula (I) which possess inhibitory activity against activating mutant forms of EGFR, and are accordingly useful for their anti-cancer activity and in methods of treatment of the human or animal body. The invention also relates pharmaceutical compositions containing them and to their use in the manufacture of medicaments of use in the production of an anti- cancer effect in a warm-blooded animal such as man.
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SYK INHIBITORS (Thu, 05 Jul 2018)
The present disclosure relates to compounds that are Syk inhibitors and to their use in the treatment of various disease states, including cancer and inflammatory conditions. In particular embodiments, the structure of the compounds is given by Formula I: wherein R 1 , R 2 , R 3 , and R 4 are as described herein. The present disclosure further provides pharmaceutical compositions that include a compound of Formula I, or pharmaceutically acceptable salts or co-crystals thereof, and methods of using these compounds and compositions to treat conditions mediated by Syk.
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INHIBITORS OF SOX18 PROTEIN ACTIVITY FOR TREATING ANGIOGENESIS- AND/OR LYMPHANGIOGENESIS-RELATED DISEASES (Fri, 29 Jun 2018)
Disclosed are compounds of a formula provided herein that show efficacy in the inhibition of SOX18 protein activity, and in particular with respect to the ability of SOX18 to bind DNA and/or particular protein partners. Further, methods of treating angiogenesis- and/or lymphangiogenesis-related diseases, disorders or conditions, such as cancer metastasis and vascular cancers, are provided herein.
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GANGLIOSIDE CARBOHYDRATE STRUCTURES AND USES THEREOF (Fri, 29 Jun 2018)
The present invention provides methods and compositions related to multivalent carbohydrate antigen structures comprising cancer or infection associated ganglioside carbohydrate antigens. Said carbohydrate structures may be used to induce immunity against said carbohydrate antigens. In some embodiments, carbohydrate structures may be administered to a subject thereby inducing immunity in the subject, for example, the administration of a vaccine comprising said carbohydrate structure. Also provided are methods to induce an immune response in a subject in need thereof by administering said carbohydrate structure. Further provided are methods of producing an antibody or TCR that bind said carbohydrate antigens.
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BENZIMIDAZOLE DERIVATIVES, PREPARATION METHODS AND USES THEIROF (Fri, 29 Jun 2018)
The present invention relates to benzimidazole compounds useful in treating for protein kinase-associated disorders. There is also a need for compounds useful in the treatment or prevention of one or more symptoms of cancer, transplant rejections. Furthermore, there is a need for methods for modulating the activity of protein kinases, such as CDK4 and/or CDK6, using the compounds provided herein.
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INHIBITORS OF MUTANT ISOCITRATE DEHYDROGENASES AND COMPOSITIONS AND METHODS THEREOF (Fri, 29 Jun 2018)
The invention provides novel chemical compounds useful for treating cancer, or a related disease or disorder thereof, and pharmaceutical composition and methods of preparation and use thereof.
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4-AMINO-2-PYRIDO-BICYCLIC PYRIMIDINES AND USE THEREOF AS TOPOISOMERASE II INHIBITORS (Fri, 29 Jun 2018)
The present invention concerns 4-amino-2-pyrido-bicyclic pyrimidines as type II topoisomerase inhibitors and use thereof as medicaments especially in the treatment of cancer. The invention also provides a method for the manufacture of 4- amino-2-pyrido bicyclic pyrimidines.
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AMINO-TRIAZOLOPYRIDINE COMPOUNDS AND THEIR USE IN TREATING CANCER (Fri, 29 Jun 2018)
The specification generally relates to compounds of Formula (I) and pharmaceutically acceptable salts thereof, where R1 and R2 have any of the meanings defined herein. The specification also relates to the use of such compounds and salts thereof to treat or prevent DNA-PK mediated disease, including cancer. The specification further relates to pharmaceutical compositions comprising such compounds and salts; kits comprising such compounds and salts; methods of manufacture of such compounds and salts; intermediates useful in the manufacture of such compounds and salts; and to methods of treating DNA-PK mediated disease, including cancer, using such compounds and salts.
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A MONOCLONAL ANTIBODY TARGETING A UNIQUE SIALOGLYCOSILATED CANCER-ASSOCIATED EPITOPE OF CD43 (Fri, 29 Jun 2018)
The present invention relates to a monoclonal mouse antibody targeting a unique sialoglycosylated cancer-associated epitope of CD43, produced by the hybridoma cell deposited under ICLC accession number ICLC PD n° 16001. Furthermore, the invention relates to an antibody, comprising a heavy chain variable region comprising complementarity determining regions CDRH1, CDRH2 and CDRH3, and a light chain variable region comprising complementarity determining regions CDRL1, CDRL2 and CDRL3, wherein CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 comprise the amino acid sequences GFTFSSFGMH, YISSGSGNFYYVDTVKG, STYYHGSRGAMDY, SASSSVSSMYWY, DTSKMAS, and QQWSSYPPIT, respectively. In addition, the invention relates to antibodies recognizing the same epitope.
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PROTEASOME INHIBITING ß-LACTAM PRODRUGS USEFUL FOR THE TREATMENT OF CANCER AND NEURODEGENERATIVE DISORDERS (Fri, 29 Jun 2018)
The present invention relates generally to proteasome inhibiting β-lactam compounds useful for the treatment of cancer and neurodegenerative disorders. The invention also provides pharmaceutical compositions and extended release formulations of said compounds, and medical uses of said compounds and/or pharmaceutical compositions to treat cancer and neurodegenerative disorders.
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PYRAN DERVATIVES AS CYP11A1 (CYTOCHROME P450 MONOOXYGENASE 11A1) INHIBITORS (Fri, 29 Jun 2018)
Compounds of formula (I) wherein R1, R2,R3,R4,R5,R23,R24,L, A and Bare as defined in claim 1, or pharmaceutically acceptable salts thereof are disclosed. The compounds of formula (I) possess utility as cytochrome P450 monooxygenase 11A1(CYP11A1) inhibitors. The compounds are useful as medicaments in the treatment of steroidreceptor, particularly androgen receptor,dependent diseases and conditions, such asprostate cancer.
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MODULATORS OF INDOLEAMINE 2,3-DIOXYGENASE (Fri, 29 Jun 2018)
Provided are IDO inhibitor compounds of Formula (I) and pharmaceutically acceptable salts thereof, their pharmaceutical compositions, their methods of preparation, and methods for their use in the prevention and/or treatment of diseases such as chronic viral infection, chronic bacterial infections, cancer, sepsis or a neurological disorder.
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SUBSTITUTED MORPHOLINE DERIVATIVES AS ROR GAMMA MODULATORS (Fri, 29 Jun 2018)
The present disclosure is directed to compounds of formula (I) and pharmaceutically acceptable salts thereof, wherein ring A, R1, R2, R3, X1, X2, m and n are as defined herein, which are active as modulators of retinoid-related orphan receptor gamma t (RORyt). These compounds prevent, inhibit, or suppress the action of RORyt and are therefore useful in the treatment of RORyt mediated diseases, disorders, syndromes or conditions such as, e.g., pain, inflammation, COPD, asthma, rheumatoid arthritis, colitis, multiple sclerosis, psoriasis, neurodegenerative diseases and cancer. (I)
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METHODS AND ARTIFICIAL TUMORS FOR VALIDATING AN ANTITUMOR IMMUNE RESPONSE (Fri, 29 Jun 2018)
The invention provides methods for validating an antitumor response by growing and maintaining artificial 3D tumors under conditions that replicate the microenvironment of the naturally occurring parent tumor as found, in situ, in a subject diagnosed with a tumor or cancer. The artificial 3D tumors are obtained from the subject and once established are tested for susceptibility to proposed anticancer treatments, such as treatments personalized to the subject.
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AMINE-SUBSTITUTED HETEROCYCLIC COMPOUNDS AS EHMT2 INHIBITORS AND METHODS OF USE THEREOF (Fri, 29 Jun 2018)
The present disclosure relates to amine-substituted heterocyclic compounds. The present disclosure also relates to pharmaceutical compositions containing these compounds and methods of treating a disorder (e.g., cancer) via inhibition of a methyltransferase enzyme selected from EHMT1 and EHMT2, by administering an amine-substituted heterocyclic heterocyclic compound disclosed herein or a pharmaceutical composition thereof to subjects in need thereof. The present disclosure also relates to the use of such compounds for research or other non-therapeutic purposes.
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COMPOUNDS USEFUL AS IMMUNOMODULATORS (Fri, 29 Jun 2018)
The present disclosure generally relates to compounds useful as immunomodulators. Provided herein are compounds, compositions comprising such compounds, and methods of their use. The disclosure further pertains to pharmaceutical compositions comprising at least one compound according to the disclosure that are useful for the treatment of various diseases, including cancer and infectious diseases.
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AZAINDENOISOQUINOLINE COMPOUNDS AND USES THEREOF (Fri, 29 Jun 2018)
Tyrosyl-DNA Phosphodiesterases 1 and 2 (Tdp1 and Tdp2) can repair damaged DNA resulting from topoisomerase inhibitors and a variety of other DNA-damaging agents. Both Tdp1 and Tdp2 inhibition could hypothetically potentiate the cytotoxicities of topoisomerase inhibitors. Series of 7-azaindenoisoquinolines that act as triple inhibitors of Top1, Tdp1 and Tdp2 are disclosed. Also described are methods for treating patients of a cancer using the disclosed azaindenoisoquinoline compounds or a pharmaceutical formulation thereof.
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THIENOPYRROLE DERIVATIVES FOR USE IN TARGETING PROTEINS, COMPOSITIONS, METHODS, AND USES THEREOF (Fri, 29 Jun 2018)
The present invention provides compounds that modulate protein function, to restore protein homeostasis, including cytokine, CKla, GSPTl, aiolos, and/or ikaros activity, and cell-cell adhesion. The invention provides methods of modulating protein-mediated diseases, such as cytokine-mediated diseases, disorders, conditions, or responses. Compositions, including in combination with other cytokine and inflammatory mediators, are provided. Methods of treatment, amelioration, or prevention of diseases, disorders, or conditions associated with a protein, such as diseases, disorders, and conditions associated with cytokines, including inflammation, fibromyalgia, rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, psoriasis, psoriatic arthritis, inflammatory bowel diseases, Crohn's disease, ulcerative colitis, uveitis, inflammatory lung diseases, chronic obstructive pulmonary disease, Alzheimer's disease, and cancer, are provided.
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PEPTIDE-ANTIBODY COMPOSITIONS AND METHODS OF USE THEREOF (Fri, 29 Jun 2018)
Peptide-antibody complexes, including fusions and conjugates, that target or accumulate in target cells, such as tumors and diseased cells, or enhance the immune system are disclosed. In some embodiments, such complexes function as platforms for attaching and targeting one or more therapeutic agents or detectable agents, including radioisotopes, detectable labels, and/or cytotoxic agents, to target cells in the central nervous system or across the blood brain barrier, cancerous cells, or target cells recognized by the antibody in such complexes. In some complexes, the peptide serves as the targeting mechanism, while other embodiments contemplate the antibody as the targeting mechanism. Peptides and/or antibodies can be engineered to deliver various effector functions in various embodiments. Peptide-antibody complexes that function as immunotherapies and enhance a body's immune system in detecting and/or destroying diseased cells or pathogens are also disclosed. Pharmaceutical compositions and uses of peptide-antibody complexes are further disclosed.
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DIMERS OF COVALENT NFKB INHIBITORS (Fri, 29 Jun 2018)
Provided herein are compounds and methods for modulating the NFĸB pathway. More particularly, provided are inhibitors of the NFĸB pathway and the uses of such inhibitors in regulating diseases and disorders, e.g., to treat cancer, autoimmune diseases, inflammatory diseases, diabetes, cardiovascular diseases, or neurological diseases.
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SYNERGISTIC INIHIBITION OF TUMOR CELL PROLIFERATION INDUCED BY COMBINED TREATMENT OF METFORMIN COMPOUNDS AND IRON CHELATORS (Fri, 29 Jun 2018)
The present invention is directed to combination therapy comprising metformin or mito-metformin compounds with at least one iron chelating agent for the treatment of cancer and pharmaceutical compositions thereof.
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PYRIDINE DERIVATIVES AS IMMUNOMODULATORS (Fri, 29 Jun 2018)
Disclosed are compounds of Formula (I), methods of using the compounds as immunomodulators, and pharmaceutical compositions comprising such compounds. The compounds are useful in treating, preventing or ameliorating diseases or disorders such as cancer or infections.
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HETEROCYCLIC COMPOUNDS DERIVATIVES AS PD-L1 INTERNALIZATION INDUCERS (Fri, 29 Jun 2018)
Disclosed are compounds of Formula (I'), methods of using the compounds as immunomodulators, and pharmaceutical compositions comprising such compounds. The compounds inhibit PD-1/PD-L1 interaction and are useful in treating, preventing or ameliorating diseases or disorders such as cancer or infections.
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BENZOOXAZOLE DERIVATIVES AS IMMUNOMODULATORS (Fri, 29 Jun 2018)
Disclosed are compounds of Formula (I), methods of using the compounds as immunomodulators, and pharmaceutical compositions comprising such compounds. The compounds are useful in treating, preventing or ameliorating diseases or disorders such as cancer or infections.
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ECTONUCLEOTIDASE INHIBITORS AND METHODS OF USE THEREOF (Fri, 29 Jun 2018)
The invention relates to novel heterocyclic compounds and pharmaceutical preparations thereof. The invention further relates to methods of treating or preventing cancer using the novel heterocyclic compounds of the invention.
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BICYCLIC HETEROAROMATIC COMPOUNDS AS IMMUNOMODULATORS (Fri, 29 Jun 2018)
Disclosed are compounds of Formula (I), methods of using the compounds as immunomodulators, and pharmaceutical compositions comprising such compounds. The compounds are useful in treating, preventing or ameliorating diseases or disorders such as cancer or infections.
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COMPOUNS, COMPOSITIONS AND METHODS OF USE (Fri, 29 Jun 2018)
Herein, compounds, compositions and methods for modulating inclusion formation and stress granules in cells related to the onset of neurodegenerative diseases, musculoskeletal diseases, cancer, ophthalmological diseases, and viral infections are described.
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COMPOSITIONS AND METHODS FOR INHIBITING ARGINASE ACTIVITY (Fri, 29 Jun 2018)
The disclosure relates to a novel class of compounds that exhibit activity inhibitory activity toward arginase, and pharmaceutical compositions comprising the compounds of the disclosure. Also provided herein are methods of treating cancer with the arginase inhibitors of the disclosure.
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THERAPEUTICALLY ACTIVE COMPLEXES (Fri, 29 Jun 2018)
A biologically active complex comprising a peptide of up to 50 amino acids in length which comprises an alpha-helical domain of a protein which has membrane perturbing activity or a variant thereof which lacks cysteine residues, and oleic acid or a salt thereof, provided the protein is other than alpha-lactalbumin. Complexes of this type are useful in therapy, in particular cancer therapy.
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LYMPHOTOXIN-BETA RECEPTOR-BINDING AGENTS, TARGETING ANTIBODIES, AND USES THEREOF (Fri, 29 Jun 2018)
Polypeptides, agents, and molecules that bind lymphotoxin-beta receptor (LTβR) and/or tumor- associated antigens are disclosed. The polypeptides, agents, or molecules may include, without limitation, fusion or single-chain lymphotoxin-αββ polypeptides and homodimer and heterodimer molecules comprising the lymphotoxin-αββ polypeptides. Antibodies that specifically bind B7-H4 and P-CADHERIN are also disclosed. Also disclosed are methods of using the polypeptides, agents, molecules, or antibodies for inducing and/or enhancing the immune response, as well as methods for the treatment of diseases such as cancer.
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Sulfonyl amide derivatives for the treatment of abnormal cell growth (Fri, 29 Jun 2018)
The present invention relates to a compound of the formula I wherein R1 to R6 , A, B, n and m are as defined herein. Such novel sulfonyl amide derivatives are useful in the treatment of abnormal cell growth, such as cancer, in mammals. This invention also relates to a method of using such compounds in the treatment of abnormal cell growth in mammals, especially humans, and to pharmaceutical compositions containing such compounds.
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A COMPOUND ISOLATED FROM ISODON FORRESTII VAR. FORRESTII AND PREPARATION METHOD AND APPLICATIONS THEREOF (Thu, 28 Jun 2018)
The present invention discloses a compound of Formula I or pharmaceutically acceptable salt thereof and its preparation method and applications. The new structure of the compound of formula I has not been reported in literature. The compound of formula I is isolated from Isodon forrestii var. forrestii and is a compound functioning as a Trxl selective inhibitor. The present invention further discloses a pharmaceutical composition, preparation of the compound of Formula I and its use for preventing or treating cancer. Iso A of the present invention has the advantages of low toxicity, high safety and strong pharmacological effect, which suggests a potential prospect in pharmaceutical applications.
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PROTEASOME INHIBITING SS-LACTAM PRODRUGS USEFUL FOR THE TREATMENT OF CANCER AND NEURODEGENERATIVE DISORDERS (Thu, 28 Jun 2018)
The present invention relates generally to proteasome inhibiting ²-lactam compounds useful for the treatment of cancer and neurodegenerative disorders. The invention also provides pharmaceutical compositions and extended release formulations of said compounds, and medical uses of said compounds and/or pharmaceutical compositions to treat cancer and neurodegenerative disorders.
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HYDROXYTRIAZINE COMPOUND AND MEDICAL USE THEREOF (Thu, 28 Jun 2018)
The present invention provides a compound having an mPGES-1 inhibitory activity and useful for the prophylaxis or treatment of pain, rheumatism, osteoarthritis, fever, Alzheimer's disease, multiple sclerosis, arteriosclerosis, glaucoma, ocular hypertension, ischemic retinal disease, systemic scleroderma and/or cancer including colorectal cancer. The present invention relates to a compound of formula [I-a], [I-b] or [I-c] or a pharmaceutically acceptable salt thereof: wherein each symbol is as defined in the specification.
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ARYL AND HETEROARYL FUSED LACTAMS (Thu, 28 Jun 2018)
This invention relates to compounds of general formula (I) in which R 1 , R 2 , U, V, L, M, R 5 , m, X, Y and Z are as defined herein, and the pharmaceutically acceptable salts thereof, to pharmaceutical compositions comprising such compounds and salts, and to methods of using such compounds, salts and compositions for the treatment of abnormal cell growth, including cancer.
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Compounds as NIK inhibitors (Wed, 27 Jun 2018)
<p id="p-0001" num="0000">The present invention relates to pharmaceutical agents useful for therapy and/or prophylaxis in a mammal, and in particular to inhibitors of NF-κB-inducing kinase (NIK—also known as MAP3K14) useful for treating diseases such as cancer, inflammatory disorders, metabolic disorders and autoimmune disorders. The invention is also directed to pharmaceutical compositions comprising such compounds, to processes to prepare such compounds and compositions, and to the use of such compounds or pharmaceutical compositions for the prevention or treatment of diseases such as cancer, inflammatory disorders, metabolic disorders including obesity and diabetes, and autoimmune disorders.</p>
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AMINOPYRAZOLES AS JANUS KINASE INHIBITORS (Fri, 22 Jun 2018)
The instant invention provides compounds which are JAK inhibitors, and as such are useful for the treatment of JAK-mediated diseases such as rheumatoid arthritis, asthma, COPD and cancer.
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7-PHENYLETHYLAMINO-4H-PYRIMIDO[4,5-D][1,3]OXAZIN-2-ONE COMPOUNDS AS MUTANT IDH1 AND IDH2 INHIBITORS (Fri, 22 Jun 2018)
A compound, as defined herein, or pharmaceutical composition containing the compound, for use in treating IDH1 or IDH2 mutant cancer and having the structure: (I).
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TETRAHYDROQUINOLINE-BASED BROMODOMAIN INHIBITORS (Fri, 22 Jun 2018)
In one aspect, compounds and compositions that modulate a bromodomain and methods of making and using same are disclosed. The disclosed compounds and compositions can be useful for disorders associated with inhibition of a bromodomain such as, for example, cancer. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.
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COMPOSITIONS AND METHODS FOR TREATING CANCER (Fri, 22 Jun 2018)
Disclosed herein, inter alia, are compositions and methods for modulating Ras and treating cancer.
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AMINOPYRAZOLES AS SELECTIVE JANUS KINASE INHIBITORS (Fri, 22 Jun 2018)
The instant invention provides compounds of formula I which are selective JAK inhibitors, and as such are useful for the treatment of JAK-mediated diseases such as atopic dermatitis, arthritis, and cancer.
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AZEPANE INHIBITORS OF MENIN-MLL INTERACTION (Fri, 22 Jun 2018)
The present invention relates to pharmaceutical agents useful for therapy and/or prophylaxis in a mammal, and in particular to azepane compounds, pharmaceutical composition comprising such compounds, and their use as menin/MLL protein/protein interaction inhibitors, useful for treating diseases such as cancer, myelodysplastic syndrome (MDS) and diabetes.
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N-OXIDE HETEROCYCLES FOR USE IN THE TREATMENT OF CANCER AND BACTERIAL DISEASES (Fri, 22 Jun 2018)
The invention provides compounds of general formula (P), and their pharmaceutically acceptable salts: (Formula (I')) wherein X is an N-oxide functionality (N+-0"), or CH; Z is a group susceptible to hydrolytic and/or enzymatic cleavage in vivo to form a group selected from -OH, -COOH, -CONH2, -O-Q-COOH and -0-Q-CONH2 (where Q is a straight chained or branched alkylene group, preferably Ci-3 alkylene, e.g. methylene), and Z is optionally linked to one or more targeting groups; Ri and R2 are independently selected from hydrogen, lower alkyl (e.g. C1 -6 alkyl), halogen (e.g. F, CI, Br, I), an acidic group which is -COOH, -S03H, -P03H2 or -B(OH)2; and an aryl group (e.g. phenyl); or R] and R2, together with the intervening carbon atoms, form an optionally substituted aromatic group; each W is independently selected from lower alkyl (e.g. Ci-6 alkyl), halogen (e.g. F, CI, Br, I), OH, and an acidic group which is -COOH, -S03H, -P03H2 or -B(OH)2; and p is an integer from 0 to 3. Such compounds find particular use as anti-neoplastic and anti-infective agents.
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CD39 vascular isoform targeting agents (Fri, 22 Jun 2018)
The present disclosure relates to antigen-binding compounds that inhibit CD39. The disclosure also relates to cells producing such compounds; methods of making such compounds, and antibodies, fragments, variants, and derivatives thereof; pharmaceutical compositions comprising the same; methods of using the compounds to diagnose, treat or prevent diseases, e.g. cancer.
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Heterocycle compounds and uses thereof (Fri, 22 Jun 2018)
Compounds having the general formula (I) and pharmaceutical compositions that can be used as Bruton's Tyrosine Kinase (BTK), ITK, JAK3, and selective mutant epidermal growth factor receptor tyrosine kinase (EGFR-TK) inhibitor and their uses in the treatment of related diseases and disorders such as cancer.
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Metal complexed therapeutic agents and lipid-based nanoparticulate formulations thereof (Fri, 22 Jun 2018)
Provided herein is a pharmaceutical formulation for delivery of a therapeutic agent having a metal complexation moiety and a solubility in water or a metal ion solution of less than 1 mg/ml. Said formulation comprises the therapeutic agent and a metal ion complexed inside a lipid-based nanoparticle formulation.
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Novel pyrrolo[3,2-c]pyridine-6-amino derivatives (Fri, 22 Jun 2018)
The present invention relates to novel pyrrolo[3,2-c]pyridine-6-amino derivatives that inhibit the spindle checkpoint function of Monospindle 1 (Mps1 – also known as TTK) kinases. In particular, the present invention relates to isopropyl 6-(2-methoxy-4-(1-5 methyl-1H-1,2,3-triazol-5-yl)phenylamino)-2-(1-methyl-1H-pyrazol-4-yl)-1H-pyrrolo[3,2- c]pyridine-1-carboxylate and isopropyl 6-(2-methoxy-4-(1-methyl-1H-tetrazol-5- yl)phenylamino)-2-(1-methyl-1H-pyrazol-4-yl)-1H-pyrrolo[3,2-c]pyridine-1-carboxylate and their use as therapeutic agents for the treatment and/or prevention of proliferative diseases, such as cancer. The present invention also relates to processes for the 10 preparation of these compounds and to pharmaceutical compositions comprising them.
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Device and methods to diagnose pancreatic cancer (Fri, 22 Jun 2018)
The present invention relates to the field of diagnostic methods. Specifically, the present invention contemplates a method for diagnosing pancreatic cancer in a subject, a method for identifying whether a subject is in need for a therapy of pancreatic cancer or a method for determining whether a pancreatic cancer therapy is successful. The invention also relates to tools for carrying out the aforementioned methods, such as diagnostic devices.
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Targeted conjugates and particles and formulations thereof (Fri, 22 Jun 2018)
Nanoparticles and micro-particles, and pharmaceutical formulations thereof, containing conjugates of an active agent such as a therapeutic, prophylactic, or diagnostic agent attached to a targeting moiety, such as a somatostatin receptor binding moiety, via a linker have been designed. Such nanoparticles and micro-particles can provide improved temporospatial delivery of the active agent and/or improved biodistribution. Methods of making the conjugates, the particles, and the formulations thereof are provided. Methods of administering the formulations to a subject in need thereof are provided, for example, to treat or prevent cancer or infectious diseases. FIGURE 4 NCI-H69 xenograft study S Vehicle Dose given
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TRICYCLIC FUSED THIOPHENE DERIVATIVES AS JAK INHIBITORS (Fri, 22 Jun 2018)
The present invention provides tricyclic fused thiophene derivatives, as well as their compositions and methods of use, that modulate the activity of Janus kinase (JAK) and are useful in the treatment of diseases related to the activity of JAK including, for example, inflammatory disorders, autoimmune disorders, cancer, and other diseases.
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PURINE DERIVATIVES FOR USE IN THE TREATMENT OF ALLERGIC, INFLAMMATORY AND INFECTIOUS DISEASES (Thu, 21 Jun 2018)
Compounds of formula (I): wherein R 1 is C 1-6 alkylamino, C 1-6 alkoxy, or C 3-7 cycloalkyloxy; m is an integer having a value of 3 to 6; n is an integer having a value of 0 to 4; and salts thereof are inducers of human interferon. Compounds which induce human interferon may be useful in the treatment of various disorders, for example the treatment of allergic diseases and other inflammatory conditions for example allergic rhinitis and asthma, the treatment of infectious diseases and cancer, and may also be useful as vaccine adjuvants.
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BENZAMIDE DERIVATIVE AS HISTONE DEACETYLASE INHIBITOR WITH POTENT DIFFERENTIATION AND ANTI-PROLIFERATION ACTIVITY (Thu, 21 Jun 2018)
The present invention is related to the preparation and pharmaceutical use of novel benzamide derivatives as defined in the specification of formula (I) as histone deacetylase inhibitors (HDACI), their preparations and the methods of using these compounds or their pharmaceutically acceptable salt in the treatment of cell proliferative diseases, e.g. cancer and psoriasis.
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Tricyclic Derivative Compound, Method for Preparing Same, and Pharmaceutical Composition Comprising Same (Fri, 15 Jun 2018)
<p id="p-0001" num="0000">The present invention relates to novel tricyclic derivative compounds, and more specifically to tricyclic derivative compounds, optical isomers thereof, racemates thereof, or pharmaceutically acceptable salts thereof, which have excellent activity against PARP-1, tankyrase-1 or tankyrase-2. The tricyclic derivative compounds, optical isomers thereof, racemates thereof or pharmaceutically acceptable salts thereof according to the present invention have inhibitory activity against PARP-1, tankyrase-1, or tankyrase-2, and thus can be effectively used for the prevention or treatment of neuropathic pain, neurodegenerative diseases, cardiovascular diseases, diabetic neuropathy, inflammatory diseases, osteoporosis, or cancer.</p>
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SUBSTITUTED ANILINES AS CCR(4) ANTAGONISTS (Fri, 15 Jun 2018)
<p id="p-0001" num="0000">Aniline compounds are provided which bind to CCR(4) and are useful for the treatment of diseases such as allergic diseases, autoimmune diseases, graft rejection and cancer.</p>
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NOVEL COMPOUNDS (Fri, 15 Jun 2018)
<p id="p-0001" num="0000">The present invention relates to novel compounds and methods for the manufacture of inhibitors of deubiquitylating enzymes (DUBs). In particular, the invention relates to the inhibition of ubiquitin C-terminal hydrolase L1 (UCHL1). The invention further relates to the use of DUB inhibitors in the treatment of cancer and other indications. Compounds of the invention include compounds having the formula (I) or a pharmaceutically acceptable salt thereof, wherein R1 to R8 are as defined herein.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="25.99mm" wi="58.34mm" file="US20180162852A1-20180614-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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HISTONE DEMETHYLASE INHIBITORS (Fri, 15 Jun 2018)
<p id="p-0001" num="0000">The present invention relates generally to compositions and methods for treating cancer and neoplastic disease. Provided herein are substituted pyrido[3,4-d]pyrimidin-4-one derivative compounds and pharmaceutical compositions comprising said compounds. The subject compounds and compositions are useful for inhibition of histone demethylase. Furthermore, the subject compounds and compositions are useful for the treatment of cancer, such as prostate cancer, breast cancer, bladder cancer, lung cancer, melanoma, and the like.</p>
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ANTI-CEACAM6 ANTIBODIES AND USES THEREOF (Fri, 15 Jun 2018)
<p id="p-0001" num="0000">The present invention provides recombinant antigen-binding regions and antibodies and functional fragments containing such antigen-binding regions that are specific for human and <i>Macaca fascicularis </i>CEACAM6 (Carcinoembryonic antigen-related cell adhesion molecule 6, CD66c, Non-specific crossreacting antigen, NCA, NCA-50/90), and which do not significantly cross-react with the closely related human CEACAM1, human CEACAM3, and human CEACAM5. The invention further provides methods to generate this kind of antibodies. The antibodies, accordingly, can be used to treat cancer and other disorders and conditions associated with expression of the CEACAM6. The invention also provides nucleic acid sequences encoding the foregoing antibodies, vectors containing the same, pharmaceutical compositions and kits with instructions for use.</p>
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3-(BENZOIMIDAZOL-2-YL)-INDAZOLE INHIBITORS OF THE WNT SIGNALING PATHWAY AND THERAPEUTIC USES THEREOF (Fri, 15 Jun 2018)
<p id="p-0001" num="0000">Indazole compounds for treating various diseases and pathologies are disclosed. More particularly, the present disclosure concerns the use of an indazole compound or analogs thereof, in the treatment of disorders characterized by the activation of Wnt pathway signaling (e.g., cancer, abnormal cellular proliferation, angiogenesis, Alzheimer's disease, lung disease and osteoarthritis), the modulation of cellular events mediated by Wnt pathway signaling, as well as genetic diseases and neurological conditions/disorders/diseases due to mutations or dysregulation of the Wnt pathway and/or of one or more of Wnt signaling components. Also provided are methods for treating Wnt-related disease states.</p>
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CANCER THERAPY TARGETING TETRASPANIN 33 (TSPAN33) IN MYELOID DERIVED SUPPRESSOR CELLS (Fri, 15 Jun 2018)
<p id="p-0001" num="0000">Methods for treating cancer, e.g., in conjunction with anti-cancer therapy, like immunotherapy, and for identifying candidate therapeutic agents, by targeting myeloid derived suppressor cells expressing Tspan33.</p>
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2-(AZAINDOL-2-YL) BENZIMIDAZOLES AS PAD4 INHIBITORS (Fri, 15 Jun 2018)
<p id="p-0001" num="0000">Compounds of formula (I) wherein; R<sub>1 </sub>is hydrogen or C<sub>1-6</sub>alkyl; R<sub>2 </sub>is hydrogen, C<sub>1-6</sub>alkyl, perhalomethylC<sub>0-5</sub>alkyl-O—, or C<sub>1-6</sub>alkoxy; R<sub>3 </sub>is hydrogen, C<sub>1-6</sub>alkyl, or C<sub>1-6</sub>alkoxyC<sub>1-6</sub>alkyl; R<sub>4 </sub>is hydrogen, C<sub>1-6</sub>alkyl, perhalomethylC<sub>1-6</sub>alkyl; or unsubstituted C<sub>3-6</sub>cycloalkylC<sub>1-6</sub>alkyl; A is C—R<sub>5 </sub>or N; B is C—R<sub>6 </sub>or N; D is C—R<sub>7 </sub>or N; with the proviso that at least one of A, B, and D, is N; R<sub>5 </sub>is hydrogen or C<sub>1-6</sub>alkyl; R<sub>6 </sub>is hydrogen or C<sub>1-6</sub>alkyl; R<sub>7 </sub>is hydrogen, C<sub>1-6</sub>alkyl, C<sub>1-6</sub>alkoxy, or hydroxy; R<sub>8 </sub>is hydrogen or C<sub>1-6</sub>alkyl, with the proviso that one of R<sub>4 </sub>and R<sub>8 </sub>is hydrogen; R<sub>9 </sub>is hydrogen or hydroxy; R<sub>1o </sub>is hydrogen or C<sub>1-6</sub>alkyl; and salts thereof are PAD4 inhibitors and may be useful in the treatment of various disorders, for example rheumatoid arthritis, vasculitis, systemic lupus erythematosus, ulcerative colitis, cancer, cystic fibrosis, asthma, cutaneous lupus erythematosis, and psoriasis.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="30.48mm" wi="69.85mm" file="US20180161316A1-20180614-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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THIENO- AND PYRROLOPYRIMIDINE ANALOGUES AS ANTICANCER AGENTS AND METHODS OF USE THEREOF (Fri, 15 Jun 2018)
<p id="p-0001" num="0000">The present invention provides for the design and synthesis of halogenated thieno- and pyrrolopyrimidine compounds that exhibit cancer proliferation inhibitory activity and the use thereof for cancer treatment.</p>
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PROCESS METHODS FOR PHOSPHATIDYLINOSITOL 3-KINASE INHIBITORS (Fri, 15 Jun 2018)
<p id="p-0001" num="0000">A process for the synthesis of quinazolinone containing compounds which may be useful for the treatment of cancer, is hereby disclosed. In addition, compound intermediates relating to these processes are also disclosed.</p>
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COMPOUNDS FOR THE MODULATION OF MYC ACTIVITY (Fri, 15 Jun 2018)
<p id="p-0001" num="0000">The present invention provides novel compounds of Formula (I) and Formula (II) and pharmaceutically acceptable salts, solvates, hydrates, tautomers, stereoisomers, isotopically labeled derivatives, and compositions thereof. Also provided are methods and kits involving the compounds or compositions for treating or preventing proliferative diseases, e.g., cancers (e.g., breast cancer, prostate cancer, lymphoma, lung cancer, pancreatic cancer, ovarian cancer, neuroblastoma, or colorectal cancer), benign neoplasms, angio genesis, inflammatory diseases, fibrosis (e.g., polycystic kidney disease), autoinflammatory diseases, and autoimmune diseases in a subject.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="37.34mm" wi="62.99mm" file="US20180162851A1-20180614-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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NUCLEIC ACID-BASED ASSEMBLY AND USE THEREOF IN CANCER THERAPY (Fri, 15 Jun 2018)
The present invention relates to a nucleic acid-based assembly comprising: at least one nucleic acid aptamer, and at least one nucleic acid motif designed to physically capture a drug. The nucleic acid motif may comprise one or more photo-responsive moieties that effect the release of the drug upon irradiation. The aptamer and the nucleic acid motif each can be covalently linked to one or more lipids, and the lipid- modified aptamer and nucleic acid motif may form the assembly through noncovalent interaction. The invention further relates to use of the nucleic acid-based assembly in the treatment of cancer.
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COMPOUNDS AND PHARMACEUTICAL COMPOSITIONS FOR MODULATING SGK ACTIVITY, AND METHODS THEREOF (Fri, 15 Jun 2018)
The invention provides novel chemical compounds useful for treating one or more of autoimmune diseases, cancer, cardiovascular diseases, inflammatory diseases and diabetes, or a related disease or disorder thereof, and pharmaceutical composition and methods of preparation and use thereof.
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ANTI-CTLA-4 ANTIBODIES AND METHODS OF USE THEREOF (Fri, 15 Jun 2018)
The instant disclosure provides antibodies that specifically bind to CTLA-4 (e.g., human CTLA-4) and antagonize CTLA-4 function. Also provided are pharmaceutical compositions comprising these antibodies, nucleic acids encoding these antibodies, expression vectors and host cells for making these antibodies, and methods of treating a subject using these antibodies.
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ANTIBODIES AND METHODS OF USE THEREOF (Fri, 15 Jun 2018)
Provided are antibodies that specifically bind to CTLA-4 and/or PD-1 and antagonize CTLA-4 and/or PD-1 function. Also provided are pharmaceutical compositions and kits comprising these antibodies, nucleic acids encoding these antibodies, expression vectors and host cells for making these antibodies, and methods of treating a subject using these antibodies either alone or in combination.
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COMPOSITIONS AND METHODS FOR TREATING CDK4/6-MEDIATED CANCER (Fri, 15 Jun 2018)
Methods for designing heterobifunctional small molecules which selectively degrade/disrupt CDK4/6 and compositions and methods of using such degraders/disruptors to treat CDK4/6-mediated cancer are provided.
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METABOLIC PROFILING OF FIXED SAMPLES (Fri, 15 Jun 2018)
The invention provides methods and compositions to evaluate biological samples. The methods comprise obtaining a formalin fixed paraffin embedded (FFPE) preparation of the biological sample, and detecting the presence of one or more metabolites in the FFPE preparation.
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BISMUTH-GADOLINIUM NANOPARTICLES (Fri, 15 Jun 2018)
Provided herein are nanoparticle compositions (e.g., nanoparticle compositions comprising high atomic number ions) that are useful for imaging diseases in a subject as well as radiosensitizing a disease in a subject (e.g., radiosensitizing a cancer in the subject). Methods of imaging a subject, methods of treating cancer, and processes of preparing the nanoparticle compositions are also provided.
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QUINOLONE-BASED COMPOUNDS WITH ANTICANCER ACTIVITY (Fri, 15 Jun 2018)
Embodiments are directed to compounds of the formulae (I), (Ia), (Ib), (II), (IIa) (III), (IV), (V), and (VI); methods for treating cancer with one or more compounds of the formulae (I), (Ia), (Ib), (II), (IIa); (III), (IV), (V), and (VI); and methods for inhibiting a human topoisomerase with one or more compounds of the formulae (I), (Ia), (Ib), (II), (IIa); (III), (IV), (V), and (VI).
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GLUTAMINE TRANSPORT INHIBITORS AND METHODS FOR TREATING CANCER (Fri, 15 Jun 2018)
Novel compounds, compositions, and methods for modulating ASCT2 function in a patient in need thereof.
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Tetracyclic bromodomain inhibitors (Fri, 15 Jun 2018)
The present invention provides for compounds of formula (I) wherein R1 , R2 , R6, YI, y2, Y', A', A2 , A3 and A4 have any of the values defined in the specification, and pharmaceutically acceptable salts thereof, that are useful as agents in the treatment of diseases and conditions, including inflammatory diseases, cancer, and AIDS. Also provided are pharmaceutical compositions comprising one or more compounds of formula (I).
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NUCLEAR RECEPTOR MODULATORS AND THEIR USE FOR THE TREATMENT AND PREVENTION OF CANCER (Thu, 14 Jun 2018)
Disclosed are compounds which are nuclear receptor modulators that can act as antagonists to the androgen receptor, for example, a compound of Formula I: wherein R 1 to R 5 and X 1 to X 5 are as described herein, as well as pharmaceutically acceptable salts, solvates, and stereoisomers thereof. Pharmaceutical compositions comprising such compounds, as well as methods of use, and treatment for cancers, including prostate cancers, other nuclear receptor mediated cancers, and other conditions, are also disclosed.
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A MEK1 MUTATION CONFERRING RESISTANCE TO RAF AND MEK INHIBITORS (Thu, 14 Jun 2018)
Nucleic acids and proteins having a mutant MEK sequence, and methods concerning identification of patients having resistance to treatment with anti-cancer agents, specifically inhibitors of RAF or MEK are provided. Methods of treatment and for optimizing treatment for patients having a mutation in a MEK1 sequence are also provided.
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CERTAIN CHEMICAL ENTITIES, COMPOSITIONS, AND METHODS (Thu, 14 Jun 2018)
Chemical entities that are kinase inhibitors, pharmaceutical compositions and methods of treatment of cancer are described.
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2-(2,4,5-SUBSTITUTED-ANILINO)PYRIMIDINE DERIVATIVES AS EGFR MODULATORS USEFUL FOR TREATING CANCER (Thu, 14 Jun 2018)
The present invention relates to certain 2-(2,4,5-substituted-anilino)pyrimidine compounds and pharmaceutically acceptable salts thereof which may be useful in the treatment or prevention of a disease or medical condition mediated through certain mutated forms of epidermal growth factor receptor (for example the L858R activating mutant, the Exon19 deletion activating mutant and the T790M resistance mutant). Such compounds and salts thereof may be useful in the treatment or prevention of a number of different cancers. The invention also relates to pharmaceutical compositions comprising said compounds and salts thereof, especially useful polymorphic forms of these compounds and salts, intermediates useful in the manufacture of said compounds and to methods of treatment of diseases mediated by various different forms of EGFR using said compounds and salts thereof.
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INHIBITION OF CANCER CELL MOTILITY (Fri, 08 Jun 2018)
<p id="p-0001" num="0000">Provided herein are compositions and methods for inhibiting cancer cell motility and/or metastasis. In particular embodiments, KBU2046 (or an analog thereof) and one or more additional therapies (e.g., cancer therapies (e.g., hormone therapies and chemotherapies) are provided to inhibit cancer cell motility, inhibit metastasis, and/or treat cancer (e.g., prostate cancer, lung cancer, breast cancer, colon cancer, etc.).</p>
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AZA Spiro Alkane Derivatives as Inhibitors of Metalloproteases (Fri, 08 Jun 2018)
<p id="p-0001" num="0000">The present invention provides a compound of Formula I or Formula II:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="47.41mm" wi="63.75mm" file="US20180153882A1-20180607-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">enantiomer, diastereomer, prodrug, solvate, metabolite, or pharmaceutically acceptable salt thereof, wherein constituent variables are provided herein. The compounds of Formula I and II are modulators of metalloproteases and are useful in treating diseases associated with metalloprotease activity such as arthritis, cancer, cardiovascular disorders, skin disorders, inflammation and allergic conditions.</p>
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FUSED BICYCLIC PYRIMIDINE DERIVATIVES AND USES THEREOF (Fri, 08 Jun 2018)
<p id="p-0001" num="0000">The present invention provides novel compounds of Formula (I), and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, prodrugs, and compositions thereof. Also provided are methods and kits involving the inventive compounds or compositions for treating or preventing proliferative diseases (e.g., cancers (e.g., lung cancer, breast cancer, leukemia, lymphoma, melanoma, multiple myeloma, Ewing's sarcoma, osteosarcoma, brain cancer, neuroblastoma), benign neoplasms, angiogenesis, inflammatory diseases, autoinflammatory diseases, and autoimmune diseases) in a subject. Treatment of a subject with a proliferative disease using a compound or composition of the invention may inhibit the aberrant activity of a kinase (e.g. a protein kinase (e.g. a cyclin-dependent kinase (CDK) (e.g. CDK7, CDK12, or CDK13) or a lipid kinase such as a phosphatidylinositol-5-phosphate 4-kinase (PIP4K) (e.g., PI5P4Kα, PI5P4Kβ, or PI5P4Kγ)) in the subject.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="37.51mm" wi="71.54mm" file="US20180153894A1-20180607-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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Indazole inhibitors of the WNT signal pathway and therapeutic uses thereof (Fri, 08 Jun 2018)
<p id="p-0001" num="0000">Indazole compounds for treating various diseases and pathologies are disclosed. More particularly, the present invention concerns the use of an indazole compound or analogs thereof, in the treatment of disorders characterized by the activation of Wnt pathway signaling (e.g., cancer, abnormal cellular proliferation, angiogenesis, Alzheimer's disease and osteoarthritis), the modulation of cellular events mediated by Wnt pathway signaling, as well as genetic diseases due to mutations in Wnt signaling components. Also provided are methods for treating Wnt-related disease states.</p>
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EXOSOMES FOR DELIVERY OF THERAPEUTIC AGENTS (Fri, 08 Jun 2018)
The present invention provides exosomes as drug delivery vehicles, compositions comprising a therapeutic agent encapsulated within such exosomes, methods of producing such exosomes and compositions thereof, as well as methods of delivering such exosomes and compositions to a specific patient tissue or organ. The present invention also provides methods of treating a disease, disorder, or condition such as cancer, an inflammatory disease, an infectious disease, an allergic disease, or an autoimmune disease, comprising administering to a patient in need thereof a provided therapeutic-loaded exosome or a pharmaceutical composition thereof.
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METHODS OF TREATING CANCER AND REAGENTS THEREOF (Fri, 08 Jun 2018)
The present disclosure relates to methods of treating cancer and/or preventing metastasis thereof in subject suffering from cancer e.g., solid tumor cancers, and reagents therefor. The present disclosure also relates to methods of inhibiting or suppressing metastatic progression in a subject suffering from metastatic cancer e.g., a metastatic solid tumor cancer, and reagents therefor. In particular, the present disclosure relates to the use of compounds which inhibit MCL-1 activity for such treatment or prevention of cancer, including the use of such compounds in combination with other agents for treatment of cancer e.g., agents with inhibit activity of a SRC family kinase.
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3-AMINO-1,5-DIHYDRO-PYRAZOLO[3,4-D]PYRIMIDIN-4-ONES AS CYCLIN DEPENDENT KINASE INHIBITORS (Fri, 08 Jun 2018)
The present invention relates to 3-amino-pyrazolo[3,4-d]pyrimidin-4-ones particularly useful as cyclin dependent kinase (CDK) inhibitors, pharmaceutical compositions comprising the same and the use thereof in particular in the prophylaxis and/or treatment of cancer and other proliferative diseases. Furthermore the present invention relates to processes for the synthesis of said 3-amino-pyrazolo[3,4d]pyrimidin-4-ones and intermediates to be used in the processes of the present invention.
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CYCLIC PURINE DINUCLEOTIDES AS STING (STIMULATOR OF INTEFERON GENES) AGONISTS (Fri, 08 Jun 2018)
The present disclosure provides a compound having a STING (stimulator of interferon genes) agonistic activity, which may be expected to be useful as an agent for the prophylaxis or treatment of STING-related diseases, such as cancer. The present disclosure relates to a compound represented by the formula (I) wherein each symbol is as defined in the description, or a salt thereof.
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COORDINATION COMPOUNDS, SYNTHESES, NANOFORMULATION AND USE THEREOF IN ONCOLOGY (Fri, 08 Jun 2018)
The present invention relates to mononuclear coordination compounds of Au and Cu, pharmaceutical formulations based thereof, the relative method of synthesis and encapsulation of the compounds in macromolecules, supramolecular aggregates or nanostructures, as well as their use for the diagnosis and/or treatment of neoplasia. Advantageously, such coordination compounds and/or formulations may contain carbohydrates which act as "cancer-targeting moieties" thereby increasing therapeutic selectivity. Said compounds and formulations are characterized by a promising toxicological profile, a remarkable and highly-selective anti-cancer activity, as well as stability and solubility in the physiological means.
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COORDINATION COMPOUNDS, SYNTHESES, NANOFORMULATION AND USE THEREOF IN ONCOLOGY (Fri, 08 Jun 2018)
The present invention relates to mononuclear and dinuclear coordination compounds of Ru and Ga, pharmaceutical formulations based thereof, the relative method of synthesis and encapsulation of the compounds in macromolecules, supramolecular aggregates or nanostructures, as well as their use for the diagnosis and/or treatment of neoplasia. Advantageously, such coordination compounds and/or formulations may contain carbohydrates which act as "cancer-targeting moieties" thereby increasing therapeutic selectivity. Said compounds and formulations are characterized by a promising toxicological profile, a remarkable and highly-selective anti-cancer activity, as well as stability and solubility in the physiological means.
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BORONIC DERIVATIVES HYDROXAMATES AS ANTICANCER AGENTS (Fri, 08 Jun 2018)
The present disclosure relates to boronic derivatives of hydroxamate compounds, methods for making the same, methods for use as a monotherapy or in combination with one or more other therapeutic agents, for treatment of proliferative diseases such as cancer. The present disclosure also teaches the utilization of said boronic derivatives of hydroxamate s as epigenetic therapy medications with enhanced bioavailability, lower-toxicity, and longer-lasting efficacy.
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A PERILLYL ALCOHOL-3 BROMOPYRUVATE CONJUGATE AND METHODS OF TREATING CANCER (Fri, 08 Jun 2018)
NEO218 (3-bromo-2-oxo-propionic acid 4-isopropenyl-cyclohex-l-enylmethyI ester), (see formula I), is a novel molecule that was generated by covalent fusion of two unrelated agents: 3- bromopyruvate (3-BF; an alkylating agent that Inhibits cancer cell metabolism) and perillyi alcohol (POH; a natural monoterpene with anticancer properties ). Methods of synthesizing NBO218, pharmaceutical compositions comprising NBO218 and methods of treating cancer using NBO218 are also disclosed.
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METHODS OF USING SUBSTITUTED PYRAZOLE AND PYRAZOLE COMPOUNDS AND FOR TREATMENT OF HYPERPROLIFERATIVE DISEASES (Fri, 08 Jun 2018)
Disclosed are methods of treating hyperproliferative disorders such as cancer, methods of arresting the cell cycle in cancer cells, methods of inhibiting glutathione synthesis in cancer cells, and associated compounds for use and uses in medicaments. In certain embodiments, the methods, uses and compounds are provided with reference to compounds of the structural formula (I), in which X1, X2, Z1, Z2, the ring system denoted by "a", R1, L1, L2, Q, L3, R3, L4, R4, L5, and R5 are as described herein. In certain embodiments, compounds disclosed herein are especially active against cancers having a mutant KRAS gene.
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SUBSTITUTED PYRAZOLE COMPOUNDS AND METHODS OF USING THEM FOR TREATMENT OF HYPERPROLIFERATIVE DISEASES (Fri, 08 Jun 2018)
Disclosed are compounds useful, for example, in methods of treating hyperproliferative disorders such as cancer, methods of arresting the cell cycle in cancer cells, methods of inhibiting glutathione synthesis in cancer cells, and associated compounds for use and uses in medicaments. In certain embodiments, the methods, uses and compounds are provided with reference to compounds of the structural formulae (Ia), (Ib), (Ic), (Id) and (Ie), in which R1, L1, L2, Q, L3, R3, L4, R4, L5, and R5 are as described herein. In certain embodiments, compounds disclosed herein are especially active against cancers having a mutant KRAS gene.
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ANTI-HRS ANTIBODIES AND COMBINATION THERAPIES FOR TREATING CANCERS (Fri, 08 Jun 2018)
Provided are antibodies that specifically bind to human histidyl-tRNA synthetase and related therapeutic compositions and methods for treating cancer, including as standalone therapies or in combination with cancer immunotherapies, for example, immune checkpoint modulators such as PD-1 inhibitors.
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IRE1 SMALL MOLECULE INHIBITORS (Fri, 08 Jun 2018)
Provided herein are small molecule inhibitors for the targeting or IRE1 protein family members. Binding may be direct or indirect. Further provided herein are methods of using IRE1 small molecule inhibitors for use in treating or ameliorating cancer in a subject. Moreover, IRE1 small molecule inhibitors described herein are for the treatment of cancer, where the cancer is a solid or hematologic cancer.
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SMALL MOLECULE BCL-2 FUNCTIONAL CONVERTERS AS CANCER THERAPEUTICS (Fri, 08 Jun 2018)
Methods for inducing growth inhibition or apoptosis of Bcl-2-expressing cells and treatments of Bcl-2 expressing cancers are provided. Additionally, assays for agents that can induce apoptosis of Bcl-2 expressing cells are disclosed.
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RNA-CODED BISPECIFIC ANTIBODY (Thu, 07 Jun 2018)
The present application describes an antibody-coding, non-modified or modified RNA and the use thereof for expression of this antibody, for the preparation of a pharmaceutical composition, in particular a passive vaccine, for treatment of tumours and cancer diseases, cardiovascular diseases, infectious diseases, auto-immune diseases, virus diseases and monogenetic diseases, e.g. also in gene therapy. The present invention furthermore describes an in vitro transcription method, in vitro methods for expression of this antibody using the RNA according to the invention and an in vivo method.
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PROCESSES FOR THE SYNTHESIS OF DIARYLTHIOHYDANTOIN AND DIARYLHYDANTOIN COMPOUNDS (Thu, 07 Jun 2018)
Processes are provided for the synthesis of diarylthiohydantoin and diarylhydantoin compounds, such as compounds of the formula: wherein X, Y 1 , Y 2 , R 1 , and R 2 are as defined herein. Medicinal products containing the same find particular use in treating prostate cancer, including castration-resistant prostate cancer and/or hormone-sensitive prostate cancer.
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Chiral synthesis method for producing cis-imidazoline compounds for pharmaceutical use (Wed, 06 Jun 2018)
<p id="p-0001" num="0000">This invention provides a method for enantioselective synthesis of cis-imidazolines and related structures through chiral resolution. A chiral acid is used to separate enantiomeric precursors of the cis-imidazolines from a racemic mixture by selective crystallization. Both enantiomers can be cyclized into the desired cis-imidazoline by complementary pathways. Compounds can be synthesized according to the invention with an enantiomeric excess as high as 99%. Cis-imidazolines such as Nutlin-3a prepared according to this invention may be used for treating cancer, killing senescent cells, or treating senescence-associated conditions.</p>
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COMPOUNDS AND METHODS FOR TREATING CANCER (Fri, 01 Jun 2018)
<p id="p-0001" num="0000">The present application relates to compounds comprising an ester, a thioester, or a hydrazide moiety and methods of synthesizing these compounds. The present application also relates to pharmaceutical compositions containing the compounds and methods of treating cell proliferative disorders mediated by the Hh signaling pathway, such as cancer, by administering the compounds and pharmaceutical compositions to subjects in need thereof.</p>
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PHENOL DERIVATIVES TO TREAT CANCER (Fri, 01 Jun 2018)
<p id="p-0001" num="0000">The present invention relates to compounds of general formula (I)</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="31.24mm" wi="64.35mm" file="US20180148427A1-20180531-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">wherein R<sup>1</sup>-R<sup>8 </sup>take various meanings, pharmaceutical compositions containing them and their use in medicine, particularly for the treatment and/or prophylaxis of cancer.</p>
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Cycloalkyl-Linked Diheterocycle Derivatives (Fri, 01 Jun 2018)
<p id="p-0001" num="0000">The present invention relates to compounds of formula (I)</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="14.99mm" wi="75.78mm" file="US20180148441A1-20180531-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <ul id="ul0001" list-style="none"> <li id="ul0001-0001" num="0000"> <ul id="ul0002" list-style="none"> <li id="ul0002-0001" num="0000">or pharmaceutically acceptable salts thereof, wherein A, L, D, R<sup>1</sup>-R<sup>15</sup>, w, x, y, and z are defined herein. The novel cycloalkyl-linked diheterocycle derivatives that are useful in the treatment of abnormal cell growth, such as cancer, in mammals. The present invention also relates to pharmaceutical compositions containing the compounds and to methods of using the compounds and compositions in the treatment of abnormal cell growth in mammals.</li> </ul> </li> </ul> </p>
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BENDAMUSTINE DERIVATIVES AND METHODS OF USING SAME (Fri, 01 Jun 2018)
<p id="p-0001" num="0000">The present invention is directed to bendamustine esters and bendamustine amides and their use for the treatment of cancer.</p>
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NOVEL COMPOUNDS AS REARRANGED DURING TRANSFECTION (RET) INHIBITORS (Fri, 01 Jun 2018)
<p id="p-0001" num="0000">This invention relates to novel compounds which are inhibitors of the Rearranged during Transfection (RET) kinase, to pharmaceutical compositions containing them, to processes for their preparation, and to their use in therapy, alone or in combination, for the normalization of gastrointestinal sensitivity, motility and/or secretion and/or abdominal disorders or diseases and/or treatment related to diseases related to RET dysfunction or where modulation of RET activity may have therapeutic benefit including but not limited to all classifications of irritable bowel syndrome (IBS) including diarrhea-predominant, constipation-predominant or alternating stool pattern, functional bloating, functional constipation, functional diarrhea, unspecified functional bowel disorder, functional abdominal pain syndrome, chronic idiopathic constipation, functional esophageal disorders, functional gastroduodenal disorders, functional anorectal pain, inflammatory bowel disease, proliferative diseases such as non-small cell lung cancer, hepatocellular carcinoma, colorectal cancer, medullary thyroid cancer, follicular thyroid cancer, anaplastic thyroid cancer, papillary thyroid cancer, brain tumors, peritoneal cavity cancer, solid tumors, other lung cancer, head and neck cancer, gliomas, neuroblastomas, Von Hippel-Lindau Syndrome and kidney tumors, breast cancer, fallopian tube cancer, ovarian cancer, transitional cell cancer, prostate cancer, cancer of the esophagus and gastroesophageal junction, biliary cancer, adenocarcinoma, and any malignancy with increased RET kinase activity.</p>
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COMPOSITIONS AND METHODS FOR THERAPY OF PROSTATE CANCER USING DRUG COMBINATIONS TO TARGET POLYAMINE BIOSYNTHESIS AND RELATED PATHWAYS (Fri, 01 Jun 2018)
<p id="p-0001" num="0000">Provided are compositions and methods for treating prostate conditions. The methods involve administering to an individual in need thereof a composition that contains i) an inhibitor of methionine salvage pathway in prostate of the individual and ii) a polyamine analogue. The methods are for use in individuals who have been diagnosed with, or are suspected of having or at risk for developing androgen sensitive prostate cancer (AS-CaP), or Castration recurrent CaP (CR-CaP), or benign prostate hyperplasia (BPH). The disclosure includes use of inhibitors of methylthioadenosine phosphorylase (MTAP), and a polyamine analog that upregulates polyamine catabolism by increasing spermidine/spermine N1-acetyl transferase (SAT1) activity, such as methyl-thio-DADMe-Immucillin (MTDIA), and 1),N(11)-bisethylnorspermine (BENSpm), respectively. Pharmaceutical formulations that contain a combination of the inhibitor of the methionine salvage pathway and a polyamine analogue are included, as are kits that contain such agents.</p>
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GLYCAN THERAPEUTIC COMPOSITIONS AND RELATED METHODS THEREOF (Fri, 01 Jun 2018)
<p id="p-0001" num="0000">Preparations of glycan therapeutics, pharmaceutical compositions, dietary supplements and medical foods thereof are provided, and methods of using said gycan therapeutics, e.g. in cancer therapy.</p>
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2-(1H-INDAZOL-3-YL)-3H-IMIDAZO[4,5-B]PYRIDINE AND THERAPEUTIC USES THEREOF (Fri, 01 Jun 2018)
<p id="p-0001" num="0000">Indazole compounds for treating various diseases and pathologies are disclosed. More particularly, the present invention concerns the use of an indazole compound or analogs thereof, in the treatment of disorders characterized by the activation of Wnt pathway signaling (e.g., cancer, abnormal cellular proliferation, angiogenesis, fibrotic disorders, bone or cartilage diseases, and osteoarthritis), the modulation of cellular events mediated by Wnt pathway signaling, as well as genetic diseases and neurological conditions/disorders/diseases due to mutations or dysregulation of the Wnt pathway and/or of one or more of Wnt signaling components. Also provided are methods for treating Wnt-related disease states.</p>
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Novel Prodrugs And Methods Of Use Thereof (Fri, 01 Jun 2018)
<p id="p-0001" num="0000">The invention relates to compounds of use as targeted cytotoxic agents and methods of use thereof. In particular, the invention relates to prodrugs that are substantially resistant to human AKR1C3 enzyme metabolism, methods of cell ablation using said compounds and methods of treatment of cancer and other hyperproliferative disorders using said compounds.</p>
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CHOLIC ACID DERIVATIVE, AND PREPARATION METHOD AND MEDICAL USE THEREOF (Fri, 01 Jun 2018)
<p id="p-0001" num="0000">The present invention relates to a cholic acid derivative, and a preparation method and a medical use thereof. In particular, the present invention relates to a cholic acid derivative of formula (I), a stereoisomer, or a pharmaceutically acceptable salt thereof. The series of compounds can be used to treat FXR mediated diseases, including cardiovascular disease, atherosclerosis, arteriosclerosis, hypercholesterolemia, hyperlipidemia and chronic hepatitis diseases, chronic liver diseases, gastrointestinal diseases, nephrosis, heart vascular diseases, metabolic diseases, cancer (for example colorectal cancer) or neurological diseases, such as strokes and other diseases, with a wide range of medical applications, and are expected to develop into a new generation of FXR agonists.</p>
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MONOMERIC CXCL121 PEPTIDE AND USE THEREOF (Fri, 01 Jun 2018)
<p id="p-0001" num="0000">The present invention provides a CXCL12<sub>1 </sub>peptide engineered to resist peptide-induced dimerization by maintaining steric repulsion of the chemokine helix, pharmaceutical compositions thereof, and methods of using said dimer in the treatment of cancer, inflammatory disorders, autoimmune disease, and HIV/AIDS.</p>
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TGF-BETA 3 SPECIFIC ANTIBODIES AND METHODS AND USES THEREOF (Fri, 01 Jun 2018)
<p id="p-0001" num="0000">Specific binding members, particularly antibodies and fragments thereof, which bind to transforming growth factor beta 3 (TGF-β3) are provided, particularly recognizing human and mouse TGF-β3, particularly antibodies and fragments that do not recognize or bind TGF-β1 or TGF-β2. Particular antibodies are provided which specifically recognize and neutralize TGF-β3. These antibodies are useful in the diagnosis and treatment of conditions associated with activated or elevated TGF-β3, including cancer, and for modulating immune cells and immune response, including immune response to cancer or cancer antigens. The anti-TGF-β3 antibodies, variable regions or CDR domain sequences thereof, and fragments thereof may also be used in therapy in combination with chemotherapeutics, immune modulators, or anti-cancer agents and/or with other antibodies or fragments thereof. Antibodies of this type are exemplified by the novel antibodies hereof, including antibody MTGF-β3-9, MTGF-β3-12, MTGF-β3-16, MTGF-β3-17 and MTGF-β3-19, whose sequences are provided herein.</p>
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BIOSENSORS AND METHODS FOR DETECTION OF LYSOPHOSPHATIDIC ACID FOR SIGNALING OF OVARIAN CANCER (Fri, 01 Jun 2018)
<p id="p-0001" num="0000">The present disclosure relates to biosensors, kits and methods for detecting and/or quantifying lysophosphatidic acid (LPA) in a liquid sample such as a serum sample from a subject. The present disclosure also relates to linker compounds that are useful, for example, in the biosensors, kits and methods of the present disclosure and to methods for preparing a biosensor for detecting and/or quantifying lysophosphatidic acid (LPA) in a liquid sample.</p>
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TRICYCLIC FUSED THIOPHENE DERIVATIVES AS JAK INHIBITORS (Fri, 01 Jun 2018)
<p id="p-0001" num="0000">The present invention provides tricyclic fused thiophene derivatives, as well as their compositions and methods of use, that modulate the activity of Janus kinase (JAK) and are useful in the treatment of diseases related to the activity of JAK including, for example, inflammatory disorders, autoimmune disorders, cancer, and other diseases.</p>
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ISOCITRATE DEHYDROGENASE (IDH) INHIBITOR (Fri, 01 Jun 2018)
Disclosed are compounds inhibiting the conversion of α–KG to D-2-HG, pharmaceutically acceptable salts, hydrates, solvates or stereoisomers thereof and pharmaceutical compositions comprising the compounds. The compound and the pharmaceutical composition can effectively treat IDH associated diseases, including cancer.
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HALOGENATED BENZOTROPOLONES AS ATG4B INHIBITORS (Fri, 01 Jun 2018)
The present invention relates to compounds having a benzotropolone core, and compositions containing said compounds acting as ATG4B inhibitors, thereby inhibiting autophagy. Moreover, the present invention provides processes for the preparation of the disclosed compounds, as well as methods of using them, for instance as a medicine, in particular for the treatment of cell proliferative disorders, such as cancer.
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NEW NAPHTHO[2,3-B]FURAN DERIVATIVES (Fri, 01 Jun 2018)
The present invention provides a compound useful as a novel antitumor agent targeting a CSC that is important in continuous proliferation of malignant tumor, metastasis and recurrence of cancer, and its resistance to an antitumor agent; a medicament comprising the compound as an active ingredient; a pharmaceutical composition; and an antitumor agent; as well as a method of treating cancer and/or a method of preventing cancer. The present invention provides compounds represented by formula (I) : or pharmaceutically acceptable salts thereof, wherein X is an oxygen atom or sulfur atom; R1 is a hydrogen atom, an alkyl group, or the like; R2 is a halogen atom or the like; R3 is a hydrogen atom, an alkyl group, or the like; m is 0, 1, 2, 3, or 4; and n is 1, 2, 3, or 4 (with the proviso that the sum of m and n is 1, 2, 3, or 4).
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SEPARATION OF METAL IONS BY LIQUID-LIQUID EXTRACTION (Fri, 01 Jun 2018)
Provided herein are separation processes for metal ions present in aqueous solutions based on methods involving liquid-liquid extraction. The separation process involves a chelator that can selectively bind to at least one of the metals at a relatively low pH. This can be used, for example, for recovery and purification of actinides from lanthanides, separation of metal ions based on their valence, and separation of metal ions based on the pH of the extraction conditions.
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COMPOSITIONS AND METHODS FOR MODULATING PROTEASE ACTIVITY (Fri, 01 Jun 2018)
Disclosed herein, inter alia, are compositions for modulating protease activity and treating cancer.
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TETRASUBSTITUTED ALKENE COMPOUNDS AND THEIR USE (Fri, 01 Jun 2018)
Disclosed herein are compounds, or pharmaceutically acceptable salts thereof, and methods of using the compounds for treating breast cancer by administration to a subject in need thereof a therapeutically effective amount of the compounds or pharmaceutically acceptable salts thereof. The breast cancer may be an ER-positive breast cancer and/or the subject in need of treatment may express a mutant ER-α protein.
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DEGRADATION OF BRUTON'S TYROSINE KINASE (BTK) BY CONJUGATION OF BTK INHIBITORS WITH E3 LIGASE LIGAND AND METHODS OF USE (Fri, 01 Jun 2018)
The present application provides bifunctional compounds of Formula (I), or an enantiomer, diastereomer, or stereoisomer thereof, or pharmaceutically acceptable salt, hydrate, solvate, or prodrug thereof, which act as protein degradation inducing moieties for Bruton's tyrosine kinase (BTK). The present application also relates to methods for the targeted degradation of BTK through the use of the bifunctional compounds that link a ubiquitin ligase-binding moiety to a ligand that is capable of binding to BTK which can be utilized in the treatment of disorders modulated by BTK.
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DEGRADATION OF PROTEIN KINASES BY CONJUGATION OF PROTEIN KINASE INHIBITORS WITH E3 LIGASE LIGAND AND METHODS OF USE (Fri, 01 Jun 2018)
The present application provides bifunctional compounds of Formula (X): Targeting Ligand or an enantiomer, diastereomer, or stereoisomer thereof, or pharmaceutically acceptable salt, hydrate, solvate, or prodrug thereof, which act as protein degradation inducing moieties for protein kinases. The present application also relates to methods for the targeted degradation of one or more protein kinases through the use of the bifunctional compounds that link a ubiquitin ligase-binding moiety to a ligand that is capable of binding to one or more protein kinases which can be utilized in the treatment of disorders modulated by protein kinases.
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DEGRADATION OF BRUTON'S TYROSINE KINASE (BTK) BY CONJUGATION OF BTK INHIBITORS WITH E3 LIGASE LIGAND AND METHODS OF USE (Fri, 01 Jun 2018)
The present application provides bifunctional compounds of Formula (X), or an enantiomer, diastereomer, or stereoisomer thereof, or pharmaceutically acceptable salt, hydrate, solvate, or prodrug thereof, which act as protein degradation inducing moieties for Bruton's tyrosine kinase (BTK). The present application also relates to methods for the targeted degradation of BTK through the use of the bifunctional compounds that link a ubiquitin ligase-binding moiety to a ligand that is capable of binding to BTK which can be utilized in the treatment of disorders modulated by BTK.
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TETRASUBSTITUTED ALKENE COMPOUNDS AND THEIR USE FOR THE TREATMENT OF BREAST CANCER (Fri, 01 Jun 2018)
Disclosed herein are compounds, or pharmaceutically acceptable salts thereof, and methods of using the compounds for treating breast cancer by administration to a subject in need thereof a therapeutically effective amount of the compounds or pharmaceutically acceptable salts thereof. The breast cancer may be an ER-positive breast cancer and/or the subject in need of treatment may express a mutant ER-α protein.
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TARGETING KRAS INDUCED IMMUNE CHECKPOINT EXPRESSION (Fri, 01 Jun 2018)
The interaction of PD-L1 expressed on the surface of tumor cells triggers PD-1 signaling in T cells which contributes to resistance of cancers to emerging immune checkpoint therapies. The present disclosure demonstrates that KRAS-induced RAF/MEK/ERK/FRA signaling is required for PD-L1 gene expression in tumor cells. Disclosed herein are compositions for the treatment of cancer comprising modulators of KRAS signaling combined with an immunotherapeutic agent that restores the sensitivity of resistant tumor cells to the immunotherapeutic agent. For example, a combination of a KRAS-specific asymmetric interfering RNAs (aiRNAs) and an immune checkpoint inhibitor is shown to enhance tumor cell-specific T cell cytotoxicity. Methods are also described for increasing the therapeutic efficacy of existing anticancer treatments through the co-administration of a modulator of KRAS signaling.
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INHIBITORS OF CYCLIN-DEPENDENT KINASE 12 (CDK12) AND USES THEREOF (Fri, 01 Jun 2018)
The present invention provides novel compounds of Formulae (I') and (II), and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, prodrugs, and compositions thereof. Also provided are methods and kits involving the inventive compounds or compositions for treating and/or preventing proliferative diseases (e.g., cancers (e.g., leukemia, acute lymphoblastic leukemia, lymphoma, Burkitt's lymphoma, melanoma, multiple myeloma, breast cancer, Ewing's sarcoma, osteosarcoma, brain cancer, ovarian cancer, neuroblastoma, lung cancer, colorectal cancer), benign neoplasms, diseases associated with angiogenesis, inflammatory diseases, autoinflammatory diseases, and autoimmune diseases) in a subject. Treatment of a subject with a proliferative disease using a compound or composition of the invention may inhibit the aberrant activity of a kinase, such as a cyclin-dependent kinase (CDK) (e.g., CDK12), and therefore, induce cellular apoptosis and/or inhibit transcription in the subject.
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INHIBITORS OF INTERLEUKIN-1 RECEPTOR-ASSOCIATED KINASES AND USES THEREOF (Fri, 01 Jun 2018)
The present invention provides novel compounds of Formula (I'), and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, prodrugs, and compositions thereof. Also provided are methods and kits involving the inventive compounds or compositions for treating and/or preventing proliferative diseases (e.g., cancers (e.g., leukemia, lymphoma)), inflammatory diseases, autoinflammatory diseases, and autoimmune diseases in a subject. Treatment of a subject with a proliferative disease using a compound or composition of the invention may inhibit the aberrant activity of a kinase, such as an interleukin-1 receptor-associated kinase (IRAK) (e.g., IRAKI and/or IRAK4) in the subject.
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NOVEL COMPOUND HAVING BLT INHIBITORY ACTIVITY AND COMPOSITION, FOR PREVENTING OR TREATING INFLAMMATORY DISEASES, COMPRISING SAME AS ACTIVE INGREDIENT (Thu, 31 May 2018)
The present invention relates to a novel compound showing leukotriene B4 receptor 2 (BLT2) inhibitory activity and a pharmaceutical composition, for preventing or treating inflammatory diseases, comprising same as an active ingredient. The inventors identified a novel compound containing BTL2 inhibitory activity, and experimentally confirmed that the present novel compound had an excellent effect on the enhancement of the cancer cell death, on the inhibition of the metastasis and chemotactic mobility, and on the anti-asthma activity. Therefore, the present novel compound can be used as a very effective pharmaceutical component for treating the inflammatory-related diseases.
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NOVEL COMPOUND HAVING BLT INHIBITORY ACTIVITY AND COMPOSITION, FOR PREVENTING OR TREATING INFLAMMATORY DISEASES, COMPRISING SAME AS ACTIVE INGREDIENT (Thu, 31 May 2018)
The present invention relates to a novel compound showing leukotriene B4 receptor 2 (BLT2) inhibitory activity and a pharmaceutical composition, for preventing or treating inflammatory diseases, comprising same as an active ingredient. The inventors identified a novel compound containing BTL2 inhibitory activity, and experimentally confirmed that the present novel compound had an excellent effect on the enhancement of the cancer cell death, on the inhibition of the metastasis and chemotactic mobility, and on the anti-asthma activity. Therefore, the present novel compound can be used as a very effective pharmaceutical component for treating the inflammatory-related diseases.
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CYTOTOXIC PEPTIDES AND ANTIBODY DRUG CONJUGATES THEREOF (Thu, 31 May 2018)
The present invention is directed to cytotoxic pentapeptides, to antibody drug conjugates thereof, and to methods for using the same to treat cancer.
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CARBAMATE COMPOUNDS AND OF MAKING AND USING SAME (Thu, 31 May 2018)
This disclosure provides compounds and compositions which may be modulators of MAGL and/or ABHD6 and their use as medicinal agents, processes for their preparation, and pharmaceutical compositions that include disclosed compounds as at least one active agent. The disclosure also provides for method of treating a patient in need thereof, where the patient is suffering from indications such as pain, solid tumor cancer and/or obesity comprising administering a disclosed compound or composition.
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HUMANIZED MONOCLONAL ANTIBODIES AND METHODS OF USE (Thu, 31 May 2018)
The present invention comprises a humanized monoclonal antibody that binds to the human immunoglobulin heavy chain variable region germline gene VH1-69. This antibody is derived from Mab G6 and recognizes the same epitope. Moreover, the antibody is used in combination with vaccines to augment an immune response to the antigen.
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Pyrazole derivatives as NIK inhibitors (Wed, 30 May 2018)
<p id="p-0001" num="0000">The present invention relates to pharmaceutical agents useful for therapy and/or prophylaxis in a mammal, and in particular to inhibitors of NF-κB-inducing kinase (NIK—also known as MAP3K14) useful for treating diseases such as cancer, inflammatory disorders, metabolic disorders and autoimmune disorders. The invention is also directed to pharmaceutical compositions comprising such compounds, to processes to prepare such compounds and compositions, and to the use of such compounds or pharmaceutical compositions for the prevention or treatment of diseases such as cancer, inflammatory disorders, metabolic disorders including obesity and diabetes, and autoimmune disorders.</p>
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Method for overcoming drug resistance of EGFR mutation and cancerous stemness of human non-small cell lung carcinoma (Wed, 30 May 2018)
<p id="p-0001" num="0000">EGFR mutation (T790M) and cancerous stemness have shown drug resistances in human non-small-cell lung cancer (NSCLC), thus development of novel drugs in overcoming drug resistances in the NSCLC therapy is highly desired. SP101 is a novel gefitinib derivative, which can bind the ATP-binding pocket of EGFR to inhibit its EGFR kinase activity. SP101 can reduce the drug resistances of EGFR mutation (T790M) and cancerous stemness in NSCLC. SP101 induced cancer cell death and apoptosis in the gefitinib-resistant EGFR mutation (T790M) H1975 cells. SP101 inhibited phosphorylated EGFR and its downstream Survivin proteins but conversely induced Caspase 3 activation for apoptosis induction. Moreover, SP101 could decrease Oct4 protein level and reduce Survivin proteins but conversely elicited active Caspase 3 in the xenograft human H1975 lung tumors in nude mice.</p>
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METHODS AND COMPOSITIONS FOR THE DIAGNOSIS AND SELECTIVE TREATMENT OF CANCER (Fri, 25 May 2018)
<p id="p-0001" num="0000">In one aspect, provided herein are methods for treating cancer in a subject, comprising: (1) identifying in the subject the presence of a mutation in a splicing factor selected from the group consisting of U2AF1, SF3B1, SRSF2, and ZRSR2; and/or determining in the subject an increased amount of DCAF15 compared to a control, and (2) inhibiting an activity of RBM39 in the subject. In some embodiments, the inhibiting step can include promoting RBM39 degradation, preferably in a DCAF15-dependent manner. Compositions are also provided.</p>
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METABOLICALLY PROGRAMMED METAL CHELATORS AND USES THEREOF (Fri, 25 May 2018)
<p id="p-0001" num="0000">The present invention provides compounds of Formula (I), which are “metabolically programmed” metal chelators, e.g., lipophilic, absorbable (e.g., orally absorbable), and effective metal chelators that are converted in vivo to their hydrophilic, nontoxic metabolites. The present invention also provides compounds of Formula (II), which are also “metabolically programmed” metal chelators. The invention also provides pharmaceutical compositions, kits, methods, and uses that include a compound described herein. The compounds, pharmaceutical compositions, kits, and methods may be useful in treating or preventing a disease (e.g., metal overload, oxidative stress, diabetes, liver disease, heart disease, cancer, radiation injury, neurological or neurodegenerative disorder, Friedreich's ataxia (FRDA), macular degeneration, closed head injury, irritable bowel disease, reperfusion injury, metal poisoning, or infectious disease).</p>
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Imidazo-pyrimidone Compounds, and Preparation Method and Application Thereof (Fri, 25 May 2018)
<p id="p-0001" num="0000">Compounds of formula (I), imidazopyrimidine ketones, as well as preparations and applications thereof. Compounds and pharmaceutically acceptable salts thereof which stimulate the body to produce tumor necrosis factor-related apoptosis-inducing ligands, while avoiding the drawbacks of existing cancer treatments based on recombinant proteins and antibodies. Thus, they can provide novel options for the treatment of related tumors.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="26.92mm" wi="69.85mm" file="US20180141946A1-20180524-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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Imidazo[4,5-c]quinolin-2-one Compounds and Their Use in Treating Cancer (Fri, 25 May 2018)
<p id="p-0001" num="0000">The specification generally relates to compounds of Formula (I):</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="32.77mm" wi="75.27mm" file="US20180141943A1-20180524-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <ul id="ul0001" list-style="none"> <li id="ul0001-0001" num="0000"> <ul id="ul0002" list-style="none"> <li id="ul0002-0001" num="0000">and pharmaceutically acceptable salts thereof, where R<sup>1</sup>, R<sup>2</sup>, R<sup>3</sup>, R<sup>4 </sup>and R<sup>5 </sup>have any of the meanings defined herein. The specification also relates to the use of compounds of Formula (I) and salts thereof to treat or prevent ATM mediated disease, including cancer. The specification further relates to pharmaceutical compositions comprising to substituted imidazo[4,5-c]quinolin-2-one compounds and pharmaceutically acceptable salts thereof; kits comprising such compounds and salts; methods of manufacture of such compounds and salts; and intermediates useful in such manufacture.</li> </ul> </li> </ul> </p>
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ANTI-cMET ANTIBODY (Fri, 25 May 2018)
<p id="p-0001" num="0000">The invention relates to a novel antibody capable of binding specifically to the human c-Met receptor and/or capable of specifically inhibiting the tyrosine kinase activity of said receptor, with an improved antagonistic activity, said antibody comprising a modified hinge region.</p> <p id="p-0002" num="0000">The invention also relates to a composition comprising such an antibody antagonist to c-Met and its use as a medicament for treating cancer.</p>
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ANTIBODIES TO CD40 (Fri, 25 May 2018)
<p id="p-0001" num="0000">Provided herein are agonistic antibodies, or antigen binding portions thereof, that bind to human CD40. Such antibodies optionally comprise Fc regions with enhanced specificity for FcγRIIb. The invention also provides methods of treatment of cancer or chronic infection by administering the antibodies of the invention to a subject in need thereof.</p>
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APOPTOSIS-INDUCING AGENTS FOR THE TREATMENT OF CANCER AND IMMUNE AND AUTOIMMUNE DISEASES (Fri, 25 May 2018)
<p id="p-0001" num="0000">Disclosed are compounds which inhibit the activity of anti-apoptotic Bcl-xL proteins, compositions containing the compounds and methods of treating diseases during which is expressed anti-apoptotic Bcl-xL protein.</p>
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FUNCTIONALISED BENZOPYRAN COMPOUNDS AND USE THEREOF (Fri, 25 May 2018)
<p id="p-0001" num="0000">Benzopyran compounds, the preparation thereof, and their use in methods for treating cancer and reducing the incidence or risk of cancer recurrence. The cancer can be one or more of pancreatic cancer, colorectal cancer, melanoma, prostate cancer, brain cancer (including paediatric and adult), ovarian cancer, breast cancer, lung cancer, liver cancer, uterine cancer, neuroblastoma, mesothelioma, malignant ascites or peritoneal cancer.</p>
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INHIBITORS OF KRAS G12C MUTANT PROTEINS (Fri, 25 May 2018)
<p id="p-0001" num="0000">Compounds having activity as inhibitors of G12C mutant KRAS protein are provided. The compounds have the following structure (I):</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="23.54mm" wi="56.05mm" file="US20180141927A1-20180524-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">or a pharmaceutically acceptable salt, tautomer, stereoisomer or prodrug thereof, wherein R<sup>1</sup>, R<sup>2</sup>, R<sup>3a</sup>, R<sup>3b</sup>, R<sup>4a</sup>, R<sup>4b</sup>, G<sup>1</sup>, G<sup>2</sup>, L, m<sup>1</sup>, m<sup>2 </sup>and E are as defined herein. Methods associated with preparation and use of such compounds, pharmaceutical compositions comprising such compounds and methods to modulate the activity of G12C mutant KRAS protein for treatment of disorders, such as cancer, are also provided.</p>
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COMPOSITIONS AND METHODS FOR ENHANCED GENERATION OF HEMATOPOIETIC STEM/PROGENITOR CELLS (Fri, 25 May 2018)
<p id="p-0001" num="0000">The present invention relates to methods, kits and compositions for expansion of hematopoietic stem/progenitor cells and providing hematopoietic function to human patients in need thereof. In one aspect, it relates to kits and compositions comprising a Notch agonist and an aryl hydrocarbon receptor antagonist. Also provided herein are methods for expanding the hematopoietic stem/progenitor cells using kits and compositions comprising a Notch agonist and an aryl hydrocarbon receptor antagonist. The hematopoietic stem/progenitor cells expanded using the disclosed kits, compositions and methods include human umbilical cord blood stem/progenitor cells, placental cord blood stem/progenitor cells and peripheral blood stem cells. The present invention also relates to administering hematopoietic stem/progenitor cells expanded using a combination of a Notch agonist and an aryl hydrocarbon receptor antagonist to a patient for short-term and/or long-term in vivo repopulation benefits.</p>
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NOVEL COMPOUNDS (Fri, 25 May 2018)
<p id="p-0001" num="0000">Compounds of formula (I) and salts thereof:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="48.43mm" wi="56.05mm" file="US20180140695A1-20180524-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">wherein R<sub>1 </sub>is n-C<sub>4-6</sub>alkyl or C<sub>1-2</sub>alkoxyC<sub>1-2</sub>alkyl-; R<sub>2 </sub>is hydrogen or methyl; each R<sub>3 </sub>is hydroxy, halo or n-C<sub>1-3</sub>alkyl; m is an integer having a value of 2 to 4; n is an integer having a value of 0 to 3; and p is an integer having a value of 0 to 2, are inducers of human interferon. Compounds which induce human interferon may be useful in the treatment of various disorders, for example the treatment of allergic diseases and other inflammatory conditions, for example allergic rhinitis and asthma, infectious diseases and cancer, and may also be useful as vaccine adjuvants.</p>
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SELF ASSEMBLING MOLECULES FOR TARGETED DRUG DELIVERY (Fri, 25 May 2018)
<p id="p-0001" num="0000">Described herein are self-assembling protein molecules for delivering a payload, for example, a toxic anti-cancer agent, a cancer immunotherapy, a toxic anti-cancer agent and a cancer immunotherapy, or an imaging agent, to specific tissues. Examples of self-assembled proteins include clathrin and derivatives of clathrin.</p>
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Anti-Cancer DNA Vaccine Employing Plasmids Encoding Signal Sequence, Mutant Oncoprotein Antigen, and Heat Shock Protein (Fri, 25 May 2018)
<p id="p-0001" num="0000">Novel nucleic acid vectors comprising sequences encoding (a) an antigen, (b) a signal peptide, and (c) a heat shock protein, are disclosed, as are methods for using such vectors to induce antigen-specific immune responses and to treat tumors.</p>
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TETRASUBSTITUTED ALKENE COMPOUNDS AND THEIR USE (Fri, 25 May 2018)
<p id="p-0001" num="0000">Disclosed herein are compounds, or pharmaceutically acceptable salts thereof, and methods of using the compounds for treating breast cancer by administration to a subject in need thereof a therapeutically effective amount of the compounds or pharmaceutically acceptable salts thereof. The breast cancer may be an ER-positive breast cancer and/or the subject in need of treatment may express a mutant ER-α protein.</p>
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Purine Inhibitors of Human Phosphatidylinositol 3-Kinase Delta (Fri, 25 May 2018)
<p id="p-0001" num="0000">The instant invention provides compounds of formula I which are PI3K-delta inhibitors, and as such are useful for the treatment of PI3K-delta-mediated diseases such as inflammation, asthma, COPD and cancer.</p>
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INHIBITOR COMPOUNDS (Fri, 25 May 2018)
<p id="p-0001" num="0000">The present invention relates to compounds of formula I</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="30.06mm" wi="69.85mm" file="US20180141944A1-20180524-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">wherein R<sub>1</sub>, R<sub>4</sub>, Ar, W, X and Z are all as defined herein. The compounds of the present invention are known to inhibit the spindle checkpoint function of Monospindle 1 (Mps1—also known as TTK) kinases either directly or indirectly via interaction with the Mps1 kinase itself. In particular, the present invention relates to the use of these compounds as therapeutic agents for the treatment and/or prevention of proliferative diseases, such as cancer. The present invention also relates to processes for the preparation of these compounds, and to pharmaceutical compositions comprising them.</p>
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AUTOTAXIN INHIBITORS AND USES THEREOF (Fri, 25 May 2018)
<p id="p-0001" num="0000">Novel inhibitors of the enzyme autotaxin are described. The inhibitors contain one or two zinc-binding groups at the appropriate distance, Also described are uses thereof, such as for the inhibition of autotaxin activity and the treatment of various conditions (e.g., inflammatory conditions, cancer, obesity, autoimmune diseases).</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="14.48mm" wi="69.93mm" file="US20180141965A1-20180524-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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3-(3H-IMIDAZO[4,5-B]PYRIDIN-2-YL)-1H-PYRAZOLO[3,4-B]PYRIDINE AND THERAPEUTIC USES THEREOF (Fri, 25 May 2018)
<p id="p-0001" num="0000">Azaindazole compounds for treating various diseases and pathologies are disclosed. More particularly, the present invention concerns the use of an azaindazole compound or analogs thereof, in the treatment of disorders characterized by the activation of Wnt pathway signaling (e.g., cancer, abnormal cellular proliferation, angiogenesis, fibrotic disorders, bone or cartilage diseases, and osteoarthritis), the modulation of cellular events mediated by Wnt pathway signaling, as well as genetic diseases and neurological conditions/disorders/diseases due to mutations or dysregulation of the Wnt pathway and/or of one or more of Wnt signaling components. Also provided are methods for treating Wnt-related disease states.</p>
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Metal Delivery Agents and Therapeutic Uses of the Same (Fri, 25 May 2018)
<p id="p-0001" num="0000">The present invention relates to metal complexes, processes for their preparation and their use as pharmaceutical or veterinary agents, in particular for the treatment of conditions in which metal delivery can prevent, alleviate or ameliorate the condition. There are a number of clinical conditions which are caused by or associated with abnormal levels of metals (typically low metal levels). Conditions in of this type include cancer and conditions characterised by or associated with oxidative damage, more specifically neurodegenerative conditions such as Alzheimer's disease, Parkinson's disease or Huntington's disease. The invention also relates to ligands useful in the preparation of metal complexes of this type.</p>
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Therapeutic compounds (Fri, 25 May 2018)
<p id="p-0001" num="0000">The invention provides compounds and compositions that are useful for treating conditions including Alzheimer's disease, Parkinson's disease, diabetes, cancer, and psychotic disorders such as schizophrenia.</p>
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SELF-ASSEMBLED DIBLOCK COPOLYMERS COMPOSED OF PEGMEMA AND DRUG BEARING POLYMERIC SEGMENTS (Fri, 25 May 2018)
This invention relates to polymer drug conjugates according to formula I, and their use for treatment of diseases such as cancer.
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NOVEL ANTI-VIRAL AND ANTI-CANCER MOLECULE (Fri, 25 May 2018)
Novel anti-Viral and anti-Cancer molecule containing nucleobase or its derivatives or its analogues attached to an Ascorbic Acid molecule or its derivatives or its analogues with or without an oxygen bond in-between.
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NANOPARTICLE CONJUGATES AND USES THEREOF (Fri, 25 May 2018)
The targeted delivery of therapeutic agents to specific cells remains a challenge in drug delivery. Provided herein are nanoparticle-targeting agent conjugates that can be used for the targeted delivery of therapeutic agents to certain cells and target tissues. The conjugates comprise nanoparticles (e.g., metal nanoparticles such as gold nanoparticles) with organic outer shells capable of adsorbing large numbers of therapeutic agents (e.g., small molecule drugs). The nanoparticles are covalently linked to targeting agents (e.g., proteins such as antibodies). The present invention also provides formulations comprising the nanoparticle-targeting agent conjugates, and kits comprising the same. In another aspect, the present invention provides methods of using the conjugates for the delivery of therapeutic agents to cells, and the treatment and/or prevention of diseases (e.g., autoimmune diseases, infectious diseases, proliferative diseases such as cancer). In another aspect, the present invention provides methods of preparing the nanoparticle-targeting agent conjugates described herein.
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2-SUBSTITUTED AMINO-NAPHTH[1,2-D]IMIDAZOL-5-ONE COMPOUNDS OR PHARMACEUTICALLY ACCEPTABLE SALTS THEREOF CROSS REFERENCE TO RELATED APPLICATIONS (Fri, 25 May 2018)
Provided herein are therapeutic and/or prophylactic compounds for mitochondrial or oxidative stress diseases such as cancer, amyotrophic lateral sclerosis, Creutzfeldt-Jakob disease, Machado-Joseph disease, spinocerebellar ataxia, Huntington disease, Parkinson disease, Alzheimer disease, myocardial infarction, cerebral infarction, diseases related to aging, diabetes, alcoholic liver injury, chronic obstructive pulmonary disease, mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS), and the like, wherein the compound is represented by formula (1), or reduced forms thereof, or pharmaceutically acceptable salts thereof.
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5,6-DIHYDRO-11H-INDOLO[2,3-B]QUINOLIN-11-ONES AS ALK INHIBITORS (Fri, 25 May 2018)
The present disclosure provides compounds represented by Formula( I), and the pharmaceutically acceptable salts and solvates thereof, wherein R1a, R1b, R2a, R2b, R3, R4, R5, R6, R7, E and (B) are as defined as set forth in the specification. The present disclosure also provides compounds of Formula ( I) for use to treat a condition or disorder responsive to inhibition of ALK such as cancer.
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INHIBITORS OF CD73-MEDIATED IMMUNOSUPPRESSION (Fri, 25 May 2018)
Compounds that modulate the conversion of AMP to adenosine by 5'- nucleotidase, ecto, and compositions containing the compounds and methods for synthesizing the compounds, are described herein. The use of such compounds and compositions for the treatment and/or prevention of a diverse array of diseases, disorders and conditions, including cancer- and immune-related disorders, that are mediated by 5'- nucleotidase, ecto is also provided.
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ALKYL PYRROLOPYRIMIDINE ANALOGS AND METHODS OF MAKING AND USING SAME (Fri, 25 May 2018)
The present disclosure is concerned with benzo annulene compounds that are capable of inhibiting a Mer tyrosine kinase and/or a Tyro3 tyrosine kinase and methods of treating a bacterial infection, a viral infection, and/or a disorder of uncontrolled cellular proliferation such as, for example, a cancer, using these compounds. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.
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ANTI-GP73 ANTIBODIES AND IMMUNOCONJUGATES (Fri, 25 May 2018)
The present invention relates to antigen-binding molecules, preferably antibodies or antigen-binding fragments thereof, that specifically bind to a GP73, or to an antigenic portion thereof, wherein the antigen-binding molecule binds to an epitope within the extracellular part of GP73 that is internalized into a cell usually subsequent to proteolytic cleavage. The invention further relates to immunoconjugates comprising the antigen-binding molecules, in particular the anti-GP73 antibodies, or antigen-binding fragments thereof. The antigen- binding molecules and immunoconjugates of the invention may be administered alone, as a therapeutic conjugate or in combination with other naked antibodies, or with therapeutic agents, or with other immunoconjugates or as a diagnostic conjugate. The present invention also relates to nucleotide sequences encoding anti GP73 antibodies, and immunoconjugates, vectors and host cells containing the nucleotide sequences, and methods of making anti-GP73-antibodies. The antigen-binding molecules, antibodies and compositions of the invention are useful in diagnostic and therapeutic applications for diseases in which expression of GP73 is altered, in particular in which GP73 is overexpressed, such as cancer.
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ANTI-MET ANTIBODIES, BISPECIFIC ANTIGEN BINDING MOLECULES THAT BIND MET, AND METHODS OF USE THEREOF (Fri, 25 May 2018)
Provided herein are antibodies and bispecific antigen-binding molecules that bind MET and methods of use thereof. The bispecific antigen-binding molecules comprise a first and a second antigen-binding domain, wherein the first and second antigen-binding domains bind to two different (preferably non-overlapping) epitopes of the extracellular domain of human MET. The bispecific antigen-binding molecules are capable of blocking the interaction between human MET and its ligand HGF. The bispecific antigen-binding molecules can exhibit minimal or no MET agonist activity, e.g., as compared to monovalent antigen-binding molecules that comprise only one of the antigen-binding domains of the bispecific molecule, which tend to exert unwanted MET agonist activity. Also included are antibody-drug conjugates (ADCs) comprising the antibodies or bispecific antigen-binding molecules provided herein linked to a cytotoxic agent, radionuclide, or other moiety, as well as methods of treating cancer in a subject by administering to the subject a bispecific antigen-binding molecule or an ADC thereof.
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INHIBITORS OF NEDD8-ACTIVATING ENZYME (Thu, 24 May 2018)
Disclosed are chemical entities which are inhibitors of Nedd8-activating enzyme (NAE), namely, the compound {(1 S ,2 S ,4 R )-4-[(6-{[(1 R ,2 S )-5-chloro-2-methoxy-2,3-dihydro-1H-inden-1-yl]amino}pyrimidin-4-yl)oxy]-2-hydroxycyclopentyl}methyl sulfamate and pharmaceutically acceptable salts thereof; solid state forms thereof; and prodrugs thereof. Also disclosed are methods of using the chemical entities to treat disorders such as cancer.
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BICYCLIC HETEROCYCLIC AMIDE DERIVATIVE (Thu, 24 May 2018)
The present invention provides a bicyclic heterocyclic amide derivative of formula (1) wherein ring Q 1 is optionally-substituted C 6-10 aryl group, etc.; R 1 and R 2 are independently hydrogen atom, etc.; W 1 is optionally-substituted C 1-4 alkylene group; W 2 is -NR 3a C(O)-, etc. wherein R 3a is hydrogen atom or C 1-6 alkyl group; Cy 1 is the following group of formula (11), etc.; ring Q 2 is optionally-substituted benzene ring, etc.; n and m are indepndently 0, 1 or 2, provided that n and m are not simultaneously 0; X is NR 5 , etc.; R 5 is hydrogen atom, etc.; p is 1, 2, 3, 4 or 5; R 4 is, independently when two or more exist, hydrogen atom, etc.; and a pharmacologically acceptable salt thereof, which have a potent inhibitory effect on the sphere-forming ability of cancer cells and are useful as an orally-available anti-tumor agent.
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HISTONE ACETYLTRANSFERASE MODULATORS AND USES THEREOF (Thu, 24 May 2018)
The invention provides compounds and compositions comprising compounds that modulate histone acyl transferase (HAT). The invention further provides methods for treating neurodegenerative disorders, conditions associated with accumulated amyloid-beta peptide deposits, Tau protein levels, and/or accumulations of alpha-synuclein as well as cancer by administering a compound that modulates HAT to a subject.
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SUBSTITUTED 6,5-FUSED BICYCLIC HETEROARYL COMPOUNDS (Thu, 24 May 2018)
The present invention relates to substituted 6,5-fused bicyclic heteroaryl compounds. The present invention also relates to pharmaceutical compositions containing these compounds and methods of treating cancer by administering these compounds and pharmaceutical compositions to subjects in need thereof.
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DIAGNOSTIC FOR CANCER (Thu, 24 May 2018)
An agent for diagnosing cancer comprising, as an active ingredient, a compound represented by the following formula (I) (R 1 represents hydrogen atom, or a substituent; R 2 to R 7 represent hydrogen atom, hydroxyl group, an alkyl group, or a halogen atom; R 8 and R 9 represent hydrogen atom, or an alkyl group; and X represents a C 1 -C 3 alkylene group), which specifically emits fluorescence in a cancerous tissue within a short time when applied to a part in which presence of a cancerous tissue is suspected.
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Self-assembled diblock copolymers composed of pegmema and drug bearing polymeric segments (Thu, 24 May 2018)
A polymer-drug conjugate of Formula I for delivery of therapeutic agents; Wherein R1, R2 and R3 are independently selected from H or methyl; x and y are independently a number between 1-100; n is a number between 1-50; L is a cleavable linker; A and B are independently an end group or null; and D is a therapeutic agent slected from combretasatin, 5-fluorouracil, gemcitabine, chlorquine, and doxorubicin. The linker may be selected from a polyethylene glycol, an amino acid, poly amino acids, short peptides and an optionally substituted C1-10 hydrocarbon comprising a physiologically labile functional group. Polymeric assemblies formed with polymer drug conjugates of Formula I are claimed. The polymeric assembly may encapsulate additional therapeutic agents. Methods of preparing a polymer drug conjugate of Claim 1 are also claimed wherein the methods first comprise polymerizing a PEG grafted or PEG methyl ester grafted acrylate or methacrylate monomer to form a brush block copolymer. Pharmaceutical compositions comprising the polymer drug conjugate or polymeric assemblies thereof are also claimed. Claims to the polymer drug conjugate, polymeric assemblies and compositions thereof for use in the treatment or prophylaxis of cancer are also provided.
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Transplatin derivatives as anticancer agents (Wed, 23 May 2018)
<p id="p-0001" num="0000">The invention is directed to platinum(II) thione complexes of formula (I) and to methods of treating cancer using these complexes.</p>
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PRODUCTION MODULE AND METHOD, IMAGING DEVICE AND METHOD AND MRI AND/OR MRS PROGRAMS (Fri, 18 May 2018)
<p id="p-0001" num="0000">The invention relates to a module (<b>6</b>) for producing an MRI and/or MRS reference signal (S<b>0</b>), characterized in that the module comprises: <ul id="ul0001" list-style="none"> <li id="ul0001-0001" num="0000"> <ul id="ul0002" list-style="none"> <li id="ul0002-0001" num="0000">a first receiving input (<b>621</b>) for receiving of an MRI and/or MRS synchronization signal (S<b>3</b>),</li> <li id="ul0002-0002" num="0000">a second receiving input (<b>612</b>) for receiving of a time signal (S<b>8</b>) of external stimulation,</li> <li id="ul0002-0003" num="0000">supply means (<b>62</b>) for supplying of a prescribed signal (RV) representing an MRI and/or MRS virtual object (RVV),</li> <li id="ul0002-0004" num="0000">generating means for generating of the MRI and/or MRS reference signal (S<b>0</b>), for temporally varying the MRI and/or MRS reference signal (S<b>0</b>) in the same way as a time characteristic determined from the time signal (S<b>8</b>) of external stimulation and in synchronization with the MRI and/or MRS synchronization signal (S<b>3</b>),</li> <li id="ul0002-0005" num="0000">a supply output (<b>632</b>) for supplying of the MRI and/or MRS reference signal (S<b>0</b>).</li> </ul> </li> </ul> </p>
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METHODS OF TREATING PEDIATRIC CANCERS (Fri, 18 May 2018)
<p id="p-0001" num="0000">A method of treating a pediatric cancer in a subject in need thereof. The method includes administering to the subject a therapeutically effective amount of (S)—N-(5-((R)-2-(2,5-difluorophenyl)pyrrolidin-1-yl)-pyrazolo[1,5-a]pyrimidin-3-yl)-3-hydroxypyrrolidine-1-carboxamide, or a pharmaceutically acceptable salt thereof, or a combination thereof.</p>
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METHOD FOR TREATING CANCER (Fri, 18 May 2018)
<p id="p-0001" num="0000">The present invention provides a method for treating or alleviating a symptom of a disorder, e.g., immune evasion, cancer-cell induced immune dysfunction, reduced immune response, lowered inflammation, decreased expression of a major histocompatibility complex (MHC), or cancer, characterized by aberrant, misregulated, or increased Enhancer of Zeste Homolog 2 (EZH2) activity in a cell or subject in need thereof by contacting the cell or administering to the subject a therapeutically effective amount of an EZH2 inhibitor.</p>
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METHODS OF SYNTHESIZING SUBSTITUTED PURINE COMPOUNDS (Fri, 18 May 2018)
<p id="p-0001" num="0000">The present invention provides an efficient process for the synthesis of (2R,3R,4S,5R)-2-(6-amino-9H-purin-9-yl)-5-((((1r,3S)-3-(2-(5-(tert-butyl)-1H-benzo[d]imidazol-2-yl)ethyl)cyclobutyl)(isopropyl)amino)methyl)tetrahydrofuran-3,4-diol and hydrates thereof and methods for treating disorders in which DOT1-mediated protein methylation plays a part, such as cancer and neurological disorders, by administering these compounds and pharmaceutical compositions to subjects in need thereof. The present invention also provides novel crystalline forms of (2R,3R,4S,5R)-2-(6-amino-9H-purin-9-yl)-5-((((1r,3S)-3-(2-(5-(tert-butyl)-1H-benzo[d]imidazol-2-yl)ethyl)cyclobutyl)(isopropyl)amino)methyl)tetrahydrofuran-3,4-diol and hydrates thereof (Form A, Form B, and Form C), characterized by a unique X-ray diffraction pattern and Differential Scanning Calorimetry profile, as well as a unique crystalline structure.</p>
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METHODS OF SYNTHESIZING SUBSTITUTED PURINE COMPOUNDS (Fri, 18 May 2018)
<p id="p-0001" num="0000">The present invention provides an efficient process for the synthesis of (2R,3R,4S,5R)-2-(6-amino-9H-purin-9-yl)-5-((((1r,3S)-3-(2-(5-(tert-butyl)-1H-benzo[d]imidazol-2-yl)ethyl)cyclobutyl)(isopropyl)amino)methyl)tetrahydrofuran-3,4-diol and hydrates thereof and methods for treating disorders in which DOT1-mediated protein methylation plays a part, such as cancer and neurological disorders, by administering these compounds and pharmaceutical compositions to subjects in need thereof. The present invention also provides novel crystalline forms of (2R,3R,4S,5R)-2-(6-amino-9H-purin-9-yl)-5-((((1r,3S)-3-(2-(5-(tert-butyl)-1H-benzo[d]imidazol-2-yl)ethyl)cyclobutyl)(isopropyl)amino)methyl)tetrahydrofuran-3,4-diol and hydrates thereof (Form A, Form B, and Form C), characterized by a unique X-ray diffraction pattern and Differential Scanning Calorimetry profile, as well as a unique crystalline structure.</p>
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ANTI-MET ANTIBODIES, BISPECIFIC ANTIGEN BINDING MOLECULES THAT BIND MET, AND METHODS OF USE THEREOF (Fri, 18 May 2018)
<p id="p-0001" num="0000">Provided herein are antibodies and bispecific antigen-binding molecules that bind MET and methods of use thereof. The bispecific antigen-binding molecules comprise a first and a second antigen-binding domain, wherein the first and second antigen-binding domains bind to two different (preferably non-overlapping) epitopes of the extracellular domain of human MET. The bispecific antigen-binding molecules are capable of blocking the interaction between human MET and its ligand HGF. The bispecific antigen-binding molecules can exhibit minimal or no MET agonist activity, e.g., as compared to monovalent antigen-binding molecules that comprise only one of the antigen-binding domains of the bispecific molecule, which tend to exert unwanted MET agonist activity. Also included are antibody-drug conjugates (ADCs) comprising the antibodies or bispecific antigen-binding molecules provided herein linked to a cytotoxic agent, radionuclide, or other moiety, as well as methods of treating cancer in a subject by administering to the subject a bispecific antigen-binding molecule or an ADC thereof.</p>
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ADMINISTRATION OF UBIQUITIN-ACTIVATING ENZYME INHIBITOR AND CHEMOTHERAPEUTIC AGENTS (Fri, 18 May 2018)
<p id="p-0001" num="0000">Disclosed are methods for the treatment of cancer in patients in need of such treatment. The methods comprise administering to such a patient an ubiquitin-activating enzyme (UAE) inhibitor such as ((1R,2R,3S,4R)-2,3-dihydroxy-4-(2-(3-(tri-fluoromethylthio)phenyl)pyrazolo [1,5-a]pyrimidin-7-ylamino)cyclopentyl)methyl sulfamate (Compound 1) or a pharmaceutically acceptable salt in combination with one or more chemotherapeutic agents. Also disclosed are medicaments for use in the treatment of cancer.</p>
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COMBINATION THERAPY OF AN AFUCOSYLATED CD20 ANTIBODY WITH A CD79b ANTIBODY-DRUG CONJUGATE (Fri, 18 May 2018)
<p id="p-0001" num="0000">The present invention is directed to the combination therapy of an afucosylated anti-CD20 antibody with a CD79b antibody-drug conjugate for the treatment of cancer, especially to the combination therapy of CD20 expressing cancers with an afucosylated humanized B-Ly1 antibody and a CD79b antibody-drug conjugate.</p>
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5-ALA DERIVATIVES AND USE THEREOF (Fri, 18 May 2018)
<p id="p-0001" num="0000">The present invention is directed to new 5-ALA derivatives, particles and formulation thereof, related methods of preparation and methods of use thereof. In particular, the invention relates to compounds of the invention, particles and formulation thereof useful in the treatment of a cancer and/or the diagnosis of a cancer cell such as in photodynamic therapy or photodynamic diagnosis.</p>
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Site-Specific DNA-Doxorubicin Conjugates Display Enhanced Cytotoxicity to Breast Cancer Cells (Fri, 18 May 2018)
<p id="p-0001" num="0000">Doxorubicin (Dox) is widely used for breast cancer treatment but causes serious side-effects including cardiotoxicity that may adversely impact patient lifespan even if treatment is successful. The present invention relates to selective conjugation of Dox to a single site in a DNA hairpin resulting in a highly stable complex that enables Dox to be used more effectively. Selective conjugation of Dox to G15 in the hairpin loop was verified using site-specific labeling with [2-15N]-2′-deoxyguanosine in conjunction with [1H-15N] 2D NMR while 1:1 stoichiometry for the conjugate was validated by ESI-QTOF mass spectrometry and UV spectroscopy. Molecular modeling indicated covalently bound Dox also intercalated into the stem of the hairpin and stability studies demonstrated the resulting Dox-conjugated hairpin (DCH) complex had a half-life >30 h, considerably longer than alternative covalent and non-covalent complexes. Secondary conjugation of DCH with folic acid (FA) resulted in increased internalization into breast cancer cells. The dual conjugate, DCH-FA, can be used for safer and more effective chemotherapy with Dox and this conjugation strategy can be expanded to include additional anti-cancer drugs.</p>
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NANOPARTICLE CONJUGATES AND USES THEREOF (Fri, 18 May 2018)
<p id="p-0001" num="0000">The targeted delivery of therapeutic agents to specific cells remains a challenge in drug delivery. Provided herein are nanoparticle-targeting agent conjugates that can be used for the targeted delivery of therapeutic agents to certain cells and target tissues. The conjugates comprise nanoparticles (e.g., metal nanoparticles such as gold nanoparticles) with organic outer shells capable of adsorbing large numbers of therapeutic agents (e.g., small molecule drugs). The nanoparticles are covalently linked to targeting agents (e.g., proteins such as antibodies). The present invention also provides formulations comprising the nanoparticle-targeting agent conjugates, and kits comprising the same. In another aspect, the present invention provides methods of using the conjugates for the delivery of therapeutic agents to cells, and the treatment and/or prevention of diseases (e.g., autoimmune diseases, infectious diseases, proliferative diseases such as cancer). In another aspect, the present invention provides methods of preparing the nanoparticle-targeting agent conjugates described herein.</p>
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Imidazo[4,5-c]quinolin-2-one Compounds and Their Use in Treating Cancer (Fri, 18 May 2018)
<p id="p-0001" num="0000">The specification generally relates to compounds of Formula (I):</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="32.77mm" wi="75.69mm" file="US20180134699A1-20180517-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <ul id="ul0001" list-style="none"> <li id="ul0001-0001" num="0000"> <ul id="ul0002" list-style="none"> <li id="ul0002-0001" num="0000">and pharmaceutically acceptable salts thereof, where Q, R<sup>1</sup>, R<sup>2</sup>, R<sup>3</sup>, R<sup>4 </sup>and R<sup>5 </sup>have any of the meanings defined herein. The specification also relates to the use of such compounds and salts thereof to treat or prevent ATM kinase mediated disease, including cancer. The specification further relates to crystalline forms of compounds of imidazo[4,5-c]quinolin-2-one compounds and pharmaceutically acceptable salts thereof; pharmaceutical compositions comprising such compounds and salts; kits comprising such compounds and salts; methods of manufacture of such compounds and salts; intermediates useful in the manufacture of such compounds and salts; and to methods of treating ATM kinase mediated disease, including cancer, using such compounds and salts.</li> </ul> </li> </ul> </p>
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MITRAGYNINE ANALOGS AND USES THEREOF (Fri, 18 May 2018)
<p id="p-0001" num="0000">Described herein are compounds of Formulae (I′)-(II′), compounds of Formulae (I)-(II) and pharmaceutically acceptable salts thereof. Compounds of the present invention are useful for modulating opioid receptor activity. The provided compounds may have both agonistic and antagonistic effect on one or more opioid receptors. Methods of using the compounds for treating or managing pain are also described.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="191.52mm" wi="64.60mm" file="US20180134708A1-20180517-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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BROMODOMAIN INHIBITORS (Fri, 18 May 2018)
<p id="p-0001" num="0000">The present invention relates to substituted heterocyclic derivative compounds, compositions comprising said compounds, and the use of said compounds and compositions for epigenetic regulation by inhibition of bromodomain-mediated recognition of acetyl lysine regions of proteins, such as histones. Said compositions and methods are useful for the treatment of cancer and neoplastic disease.</p>
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MITO-HONOKIOL COMPOUNDS AND METHODS OF SYNTHESIS AND USE THEREOF (Fri, 18 May 2018)
<p id="p-0001" num="0000">The present invention provides mito-honokiol compounds, pharmaceutical compositions thereof, and methods of using the mito-honokiol compounds in the treatment of cancer.</p>
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TARGETED SELECTION OF PATIENTS FOR TREATMENT WITH CORTISTATIN DERIVATIVES (Fri, 18 May 2018)
<p id="p-0001" num="0000">A method for the targeted selection and treatment of patients with a tumor or cancer, comprising (i) determining whether the patient has a RUNX1 pathway impairment; and if so (ii) administering an effective amount of a cortistatin or its pharmaceutically acceptable salt or oxide, optionally in a pharmaceutically acceptable composition.</p>
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COMBINATION THERAPY WITH A PHOSPHOINOSITIDE 3-KINASE INHIBITOR WITH A ZINC BINDING MOIETY (Fri, 18 May 2018)
<p id="p-0001" num="0000">The invention provides a method of treating cancer in a subject in need thereof, comprising administering to the subject: <ul id="ul0001" list-style="none"> <li id="ul0001-0001" num="0000"> <ul id="ul0002" list-style="none"> <li id="ul0002-0001" num="0000">(a) a compound of Formula I:</li> </ul> </li> </ul> </p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="35.56mm" wi="72.56mm" file="US20180133223A1-20180517-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">or a pharmaceutically acceptable salt thereof, wherein R is hydrogen or an acyl group; and (b) a BCL-2 inhibitor; wherein the compound of Formula I or pharmaceutically acceptable salt thereof and a BCL-2 inhibitor are administered in amounts which in combination are therapeutically effective. The invention further provides a pharmaceutical composition comprising a compound of Formula I or a pharmaceutically acceptable salt thereof, a BCL-2 inhibitor and a pharmaceutically acceptable carrier or excipient.</p>
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1,4-PYRIDONE BICYCLIC HETEROARYL COMPOUNDS (Fri, 18 May 2018)
<p id="p-0001" num="0000">The present invention relates to 1,4-pyridone bicyclic heteroaryl compounds. The present invention also relates to pharmaceutical compositions containing these compounds and methods of treating cancer by administering these compounds and pharmaceutical compositions to subjects in need thereof. The present invention also relates to the use of such compounds for research or other non-therapeutic purposes.</p>
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PYRROLOBENZODIAZEPINES AND CONJUGATES THEREOF (Fri, 18 May 2018)
<p id="p-0001" num="0000">Conjugates and compounds for making conjugates which are PBD molecules linked via the N10 position are disclosed, along with the use of the conjugates for treating proliferative diseases, including cancer.</p>
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INHIBITION OF GLIADIN PEPTIDES (Fri, 18 May 2018)
<p id="p-0001" num="0000">Novel compounds and methods for the inhibition of biological barrier permeability and for the inhibition of peptide translocation across biological barriers are identified. Assays for determining modulators of biological barrier permeability and for peptide translocation across biological barriers are provided. Methods for treating diseases relating to aberrant biological barrier permeability and peptide translocation across biological barriers are provided. Such diseases include celiac disease, necrotizing enterocolitis, diabetes, cancer, inflammatory bowel diseases, asthma, COPD, excessive or undesirable immune response, gluten sensitivity, gluten allergy, food allergy, rheumatoid arthritis, multiple sclerosis, immune-mediated or type 1 diabetes mellitus, systemic lupus erythematosus, psoriasis, scleroderma and autoimmune thyroid diseases.</p>
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Compounds for the treatment or prevention of breast cancer (Fri, 18 May 2018)
<p id="p-0001" num="0000">It discloses compounds for the treatment and prevention of breast cancer, which are specifically 2-phenyl benzoselenazole compounds, pharmaceutically acceptable salts thereof and prodrugs thereof. The present invention further discloses pharmaceutical compositions containing the compounds and applications of the compounds in preparing medicines for the treatment and prevention of breast cancer in mammals. The compounds of the present invention can effectively inhibit or reduce the growth or proliferation of breast cancer cells in mammals, with no inhibition effect on the growth of part of the tested cell lines except for the breast cancer cell lines, and are highly selective.</p>
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SALTS AND PRODRUGS OF 1-METHYL-D-TRYPTOPHAN (Fri, 18 May 2018)
<p id="p-0001" num="0000">Presently provided are indoximod prodrug and salt compounds and pharmaceutical compositions comprising salts and prodrugs of indoximod, that produce enhanced plasma concentration and exposure to indoximod compared to direct administration of indoximod, in patients in need of treatment of immunosuppression mediated by the indoleamine-2,3-dioxygenase pathway, such as patients with cancer or chronic infectious diseases.</p>
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CERTAIN CHEMICAL ENTITIES, COMPOSITIONS, AND METHODS (Fri, 18 May 2018)
<p id="p-0001" num="0000">Chemical entities based on quinoxaline that are kinase inhibitors are described. Specifically quinoxaline derivatives of Formula I, containing a diarylamide or diarylurea substructure that inhibit Braf mutant kinase activity, pharmaceutical compositions containing the inhibitor compounds and methods of treatment of cancer comprising administering an effective amount of the Braf inhibitor compound are described.</p>
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THERAPEUTIC COMPOUNDS AND METHODS OF USE THEREOF (Fri, 18 May 2018)
<p id="p-0001" num="0000">The invention provides compounds that are useful for treating or preventing cancer.</p>
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METHODS TO INDUCE TARGETED PROTEIN DEGRADATION THROUGH BIFUNCTIONAL MOLECULES (Fri, 18 May 2018)
<p id="p-0001" num="0000">The present application provides bifunctional compounds which act as protein degradation inducing moieties. The present application also relates to methods for the targeted degradation of endogenous proteins through the use of the bifunctional compounds that link a cereblon-binding moiety to a ligand that is capable of binding to the targeted protein which can be utilized in the treatment of proliferative disorders. The present application also provides methods for making compounds of the application and intermediates thereof.</p>
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AZA-PHENALENE-3-KETONE DERIVATIVE, PREPARATION METHOD THEREOF, AND ITS APPLICATION AS PARP INHIBITOR (Fri, 18 May 2018)
<p id="p-0001" num="0000">Disclosed are an aza-phenalene-3-ketone derivative, a preparation method thereof and its application as a PARP inhibitor. The aza-phenalene-3-ketone derivative has the following structure:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="23.79mm" wi="36.66mm" file="US20180134722A1-20180517-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">wherein R is hydrogen, methyl, ethyl, isopropyl, benzyl or 3-methyl-3-butenyl. The aza-phenalene-3-ketone derivative has very high activity for inhibiting PARP, thereby providing a good basis for new drug research of developing a nitrogen-doped phenalene-3-ketone compound as PARP inhibitor to treat cancer.</p>
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CORTISTATIN ANALOGUES, SYNTHESES, AND USES THEREOF (Fri, 18 May 2018)
<p id="p-0001" num="0000">New cortistatin compounds and pharmaceutically acceptable salts and pharmaceutically acceptable compositions thereof are provided. These compounds can be used to treat a disorder mediated by CDK8 and/or CDK19 kinase or by the Mediator Complex generally. In particular, the compounds can be used, for example, to treat a disorder such as a tumor, cancer, or a disorder associated with angiogenesis.</p>
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Barbiturate and thiobarbiturate compounds for use in cancer therapy (Fri, 18 May 2018)
<p id="p-0001" num="0000">Provided are methods and compositions for use in therapy, and in particular for treating cancer, preferably drug-resistant cancer, and/or radiation resistant cancer. The compounds may be used for reducing tumor size in a mammalian subject and for inducing apoptosis in a tumor cell. The methods are effective on tumor cells that are resistant to drugs such as temozolomide, doxorubicin, and geldanamycin, as well as non-resistant tumor cells. Further provided are barbiturate and thiobarbiturates diene compounds for use in treating cancer, and uses, methods and compositions relating to these compounds.</p>
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NOVEL CLASS OF QUINOLONE HETEROCYCLIC AROMATIC MOLECULES FOR CANCER TREATMENT (Fri, 18 May 2018)
The invention is directed to new class of quinolone heterocyclic aromatic molecules (Renotinibs) and their use in the treatment of cancer, in particular, cancer that harbor abnormal human epidermal growth factor receptors (EGFRs).
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3-SUBSTITUTED PROPIONIC ACIDS AS ALPHA V INTEGRIN INHIBITORS (Fri, 18 May 2018)
The present invention provides compounds of Formula (I): or stereoisomers, tautomers, or pharmaceutically acceptable salts or solvates thereof, wherein all the variables are as defined herein. These compounds are antagonists to αν- containing integrins. This invention also relates to pharmaceutical compositions comprising these compounds and methods of treating a disease, disorder, or condition associated with dysregulation of ay- containing integrins, such as pathological fibrosis, transplant rejection, cancer, osteoporosis, and inflammatory disorders, by using the compounds and pharmaceutical compositions.
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CYCLOBUTANE- AND AZETIDINE-CONTAINING MONO AND SPIROCYCLIC COMPOUNDS AS ALPHA V INTEGRIN INHIBITORS (Fri, 18 May 2018)
The present invention provides compounds of Formula (I): or stereoisomers, tautomers, or pharmaceutically acceptable salts or solvates thereof, wherein all the variables are as defined herein. These compounds are antagonists to αv- containing integrins. This invention also relates to pharmaceutical compositions comprising these compounds and methods of treating a disease, disorder, or condition associated with dysregulation of av-containing integrins, such as pathological fibrosis, transplant rejection, cancer, osteoporosis, and inflammatory disorders, by using the compounds and pharmaceutical compositions.
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INDAZOLE DERIVATIVES AS αV INTEGRIN ANTAGONISTS (Fri, 18 May 2018)
The present invention provides compounds of Formula (Ia) or (Ib): or stereoisomers, tautomers, or pharmaceutically acceptable salts or solvates thereof, wherein all the variables are as defined herein. These compounds are antagonists to αV- containing integrins. This invention also relates to pharmaceutical compositions comprising these compounds and methods of treating a disease, disorder, or condition associated with dysregulation of αV-containing integrins, such as pathological fibrosis, transplant rejection, cancer, osteoporosis, and inflammatory disorders, by using the compounds and pharmaceutical compositions.
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AZOLE AMIDES AND AMINES AS ALPHA V INTEGRIN INHIBITORS (Fri, 18 May 2018)
The present invention provides compounds of Formula (I): (Formula (I)), or stereoisomers, tautomers, or pharmaceutically acceptable salts or solvates thereof, wherein all the variables are as defined herein. These compounds are inhibitors to αv-containing integrins. This invention also relates to pharmaceutical compositions comprising these compounds and methods of treating a disease, disorder, or condition associated with dysregulation of αv-containing integrins, such as pathological fibrosis, transplant rejection, cancer, osteoporosis, and inflammatory disorders, by using the compounds and pharmaceutical compositions.
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PYRROLE AMIDES AS ALPHA V INTEGRIN INHIBITORS (Fri, 18 May 2018)
The present invention provides compounds of Formula (I) or stereoisomers, tautomers, or pharmaceutically acceptable salts or solvates thereof, wherein all the variables are as defined herein. These compounds are inhibitors to αv-containing integrins. This invention also relates to pharmaceutical compositions comprising these compounds and methods of treating a disease, disorder, or condition associated with dysregulation of αv-containing integrins, such as pathological fibrosis, transplant rejection, cancer, osteoporosis, and inflammatory disorders, by using the compounds and pharmaceutical compositions.
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COMPOSITIONS AND METHODS OF MODULATING ANTI-TUMOR IMMUNITY (Fri, 18 May 2018)
The present invention provides methods of treating cancer by combination therapy with CDK4/6 inhibitors and immune checkpoint inhibition.
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RESTORATION OF TUMOR SUPPRESSION USING MRNA-BASED DELIVERY SYSTEM (Fri, 18 May 2018)
Compositions and methods for treating cancer that include administering a therapeutically effective amount of a tumor suppressor mRNA complexed with a delivery vehicle as described herein, e.g., a nanoparticle.
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ECKOL DERIVATIVES, METHODS OF SYNTHESIS AND USES THEREOF (Fri, 18 May 2018)
Provided herein are eckol derivatives, methods of synthesis thereof and pharmaceutical compositions thereof. In other embodiments, provided herein are methods of treatment, prevention, or amelioration of a variety of medical disorders such as, for example, Alzheimer's disease, microbial infections, obesity, diabetes, cancer or inflammation using the compounds and pharmaceutical compositions disclosed herein.
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ACTIVIN RECEPTOR TYPE IIA VARIANTS AND METHODS OF USE THEREOF (Fri, 18 May 2018)
The invention features polypeptides that include an extracellular ActRlla variant. In some embodiments, a polypeptide of the invention includes an extracellular ActRlla variant fused to an Fc domain monomer or moiety. The invention also features pharmaceutical compositions and methods of using the polypeptides to treat diseases and conditions involving weakness and atrophy of muscles, e.g., Duchenne muscular dystrophy, facioscapulohumeral muscular dystrophy, inclusion body myositis, amyotrophic lateral sclerosis, sarcopenia; or cancer cachexia; or metabolic diseases, e.g., obesity, Type-1 diabetes, or Type-2 diabetes.
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ACTIVIN RECEPTOR TYPE IIA VARIANTS AND METHODS OF USE THEREOF (Fri, 18 May 2018)
The invention features polypeptides that include an extracellular ActRlla variant. In some embodiments, a polypeptide of the invention includes an extracellular ActRlla variant fused to an Fc domain monomer or moiety. The invention also features pharmaceutical compositions and methods of using the polypeptides to treat diseases and conditions involving bone damage, e.g., primary osteoporosis, secondary osteoporosis, osteopenia, osteopetrosis, facture, bone cancer or cancer metastasis-related bone loss, Paget's disease, renal osteodystrophy, treatment-related bone loss, diet- related bone loss, bone loss associated with the treatment of obesity, low gravity-related bone loss, or immobility-related bone loss.
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DEGRADATION OF PROTEIN KINASES BY CONJUGATION OF PROTEIN KINASE INHIBITORS WITH E3 LIGASE LIGAND AND METHODS OF USE (Fri, 18 May 2018)
The present application provides bifunctional compounds of Formula (I), or an enantiomer, diastereomer, or stereoisomer thereof, or pharmaceutically acceptable salt, hydrate, solvate, or prodrug thereof, which act as protein degradation inducing moieties for protein kinases (e.g., Bcr-Abl). The present application also relates to methods for the targeted degradation of one or more protein kinases through the use of the bifunctional compounds that link a ubiquitin ligase-binding moiety to a ligand that is capable of binding to one or more protein kinases which can be utilized in the treatment of disorders modulated by protein kinases.
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ATG7 INHIBITORS AND THE USES THEREOF (Fri, 18 May 2018)
Disclosed are chemical entities which are compounds of formula (I) : or a pharmaceutically acceptable salt thereof, wherein R1, R2, and Ra have the values described herein. Chemical entities according to the disclosure can be useful as inhibitors of ATG7. Further provided are pharmaceutical compositions comprising a chemical entity of the disclosure and methods of using the compositions in the treatment of cancer.
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ANTI-CD46 ANTIBODIES AND METHODS OF USE (Fri, 18 May 2018)
Disclosed herein are methods of treating a subject having a cancer characterized by a modification at biomarker 1q21, which comprises administering to the subject a therapeutically effective amount of an anti-CD46 antibody.
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HETEROCYCLIC MODULATORS OF LIPID SYNTHESIS (Fri, 18 May 2018)
Compounds that are fatty acid synthesis modulators are provided. The compounds may be used to treat disorders characterized by disregulation of the fatty acid synthase function by modulating the function and/or the fatty acid synthase pathway. Methods are provided for treating such disorders including viral infections, such as hepatitis C infection, cancer and metabolic disorders, such as non-alcoholic steatohepatitis (NASH).
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HUMAN PLASMA-LIKE MEDIUM (Fri, 18 May 2018)
In some aspects, described herein are cell culture media that are useful for in vitro culture of mammalian cells. The culture media contain a variety of small organic compounds that are found in normal adult human blood. Also described are methods of using the culture media for a variety of purposes. Also described are methods of treating cancer.
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INHIBITORS OF CANCER INVASION, ATTACHMENT, AND/OR METASTASIS (Fri, 18 May 2018)
Provided herein are, inter alia, compositions that bind to a PDZ1 domain of MDA-9/Syntenin (syndecan binding protein: SDCBP), thereby inhibiting MDA-9/Syntenin activity, and methods of use of same. The compositions and methods provided herein are useful for treating cancer and preventing cancer metastasis, particularly in cancers that have increased MDA-9/Syntenin expression.
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COMBINATION OF A BRD4 INHIBITOR AND AN ANTIFOLATE FOR THE THERAPY OF CANCER (Fri, 18 May 2018)
The present invention relates to the combination of a BRD4 inhibitor with an antifolate (particularly an MTHFD1 inhibitor) for use in the treatment or prevention of cancer. The invention also relates to an antifolate (particularly an MTHFD1 inhibitor) for use in resensitizing a BRD4 inhibitor-resistant cancer to the treatment with a BRD4 inhibitor. The invention further provides a pharmaceutical composition comprising a BRD4 inhibitor, an antifolate (particularly an MTHFD1 inhibitor), and a pharmaceutically acceptable excipient. Moreover, the invention provides a method of assessing the susceptibility or responsiveness of a subject to the treatment with a BRD4 inhibitor, wherein the subject has been diagnosed as suffering from cancer or is suspected of suffering from cancer, the method comprising determining the level of nuclear folate and/or the level of expression of MTHFD1 in a sample obtained from the subject.
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PYRIMIDINONE DERIVATIVES AS CDC7 INHIBITORS (Fri, 18 May 2018)
The present invention relates to compounds of formula I as defined herein, and salts and solvates thereof, that function as inhibitors of cell division cycle 7 (Cdc7) kinase enzyme activity Formula (I). The present invention also relates to pharmaceutical compositions comprising them, and to their use in the treatment of proliferative disorders, such as cancer, as well as other diseases or conditions in which Cdc7 kinase activity is implicated.
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HEDGEHOG ANTAGONISTS HAVING ZINC BINDING MOIETIES (Thu, 17 May 2018)
The present invention provides compounds which antagonize hedgehog signaling and inhibit HDAC activity. The compounds can be used in methods of treating proliferative diseases and disorders such as cancer.
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BICYCLIC HETEROARYL DERIVATIVES AS MNK1 AND MNK2 MODULATORS AND USES THEREOF (Thu, 17 May 2018)
The present invention relates to certain compounds (e.g., imidazopyrazine, imidazopyridine, imidazopyridazine and imidazpyrimidine compounds) that act as inhibitors of the MAP kinase interacting kinases MNK2a, MNK2b, MNK1a, and MNK1b. The present invention further relates to pharmaceutical compositions comprising these compounds, and to the use of the compounds for the preparation of a medicament for the prophylaxis and treatment of diseases (e.g., proliferative diseases (e.g., cancer), inflammatory diseases, Alzheimer's disease), as well as methods of treating these diseases.
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IMMUNOMODULATORS (Sat, 12 May 2018)
The present disclosure provides compounds which are immunomodulators and thus are useful for the amelioration of various diseases, including cancer and infectious diseases.
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ZINC-γ-PGA COMPOSITIONS AND METHODS FOR TREATING CANCER (Sat, 12 May 2018)
The invention relates to pharmaceutical compositions comprising a zinc2+ salt and a γ-polyglutamic acid carrier, and, optionally, an NF-kB inhibitor as a tumor-sensitizing agent, and methods for using such compositions to treat tumors in patients. Methods include administering a liquid dosage form or a solid dosage form of a therapeutically effective amount of a Zn(ll) salt and a γ-polyglutamic acid carrier to a patient in need thereof. Methods of treating a broad spectrum of human tumors, including tumors with a drug-resistant phenotype, using the disclosed compositions are provided. Tumors that respond to the pharmaceutical compositions disclosed herein include neuroendocrine (neuroblastoma), gastric, uterine, and lung tumors.
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6-SUBSTITUTED DERIVATIVES OF HEXAMETHYLENE AMILORIDE AS INHIBITORS OF uPA AND USES THEREOF (Sat, 12 May 2018)
The present invention broadly relates to 6-substituted derivatives of hexamethylene amiloride, the preparation thereof, and their use in the treatment of diseases such as cancer.
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COMPOUNDS FOR MALT1 DEGRADATION (Sat, 12 May 2018)
Provided herein are bifunctional compounds that inhibit MALTl and/or promote targeted ubiquitination for the degradation of MALTl. In particular, provided are compounds that can bind MALTl, a protein whose activity is responsible for constitutive NF-KB signaling in certain cancers (e.g., activated B-cell diffuse large B-cell lymphoma (ABC-DLBCL)), and can assist in its degradation by recruiting an E3 ubiquitin ligase (e.g., Cereblon, VHL), which can ubiquitinate MALTl, marking it for proteasome degradation. Also provided are pharmaceutical compositions comprising the bifunctional compounds, methods of treating cancer with the bifunctional compounds, methods of promoting the degradation of MALTl, and methods of binding E3 ubiquitin ligase activity in a subject by administering a compound or composition described herein.
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COMBINATION THERAPY WITH A PHOSPHOINOSITIDE 3-KINASE INHIBITOR WITH A ZINC BINDING MOIETY (Sat, 12 May 2018)
The invention provides a method of treating cancer in a subject in need thereof, comprising administering to the subject: (a) a compound of Formula I: or a pharmaceutically acceptable salt thereof, wherein R is hydrogen or an acyl group; and (b) a BCL-2 inhibitor; wherein the compound of Formula I or pharmaceutically acceptable salt thereof and a BCL-2 inhibitor are administered in amounts which in combination are therapeutically effective. The invention further provides a pharmaceutical composition comprising a compound of Formula I or a pharmaceutically acceptable salt thereof, a BCL-2 inhibitor and a pharmaceutically acceptable carrier or excipient.
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SUBSTITUTED QUINOLINES AND METHODS FOR TREATING CANCER (Sat, 12 May 2018)
Substituted quinoline compounds, methods of making such compounds, pharmaceutical compositions and medicaments comprising such compounds, and methods of using such compounds to treat, prevent or ameliorate cancer are provided.
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AGENTS AND METHODS FOR TREATING CREB BINDING PROTEIN-DEPENDENT CANCERS (Sat, 12 May 2018)
Single chain peptides comprising either a cell penetrating HIV-TAT peptide sequence and a MYB:CBP complex interfering peptide sequence from MYB, or compsiring a cell penetrating HIV-TAT peptide sequence, a CBP binding peptide sequence from CREB and a MYB:CBP complex interfering peptide sequence from MYB, are provided for use in preventing MYB:CBP complex formation and downstream events leading to cancer, in particular a leukemia. Both L-amino acid single chain peptides and retro-inverso single chain peptides are provided.
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ARYLCYCLOPROPYLAMINE BASED DEMETHYLASE INHIBITORS OF LSD1 AND THEIR MEDICAL USE (Fri, 11 May 2018)
<p id="p-0001" num="0000">The invention relates to (hetero)aryl cyclopropylamine compounds, including particularly the compounds of formula (I) as described and defined herein, and their use in therapy, including, e.g., in the treatment or prevention of cancer, a neurological disease or condition, or a viral infection. Thus, in one specific aspect the invention relates to formulas (II), (III), (IV), (V), (VI), (VII), (VIII), (IX).</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="213.19mm" wi="74.34mm" file="US20180127406A1-20180510-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <chemistry id="CHEM-US-00002" num="00002"> <img id="EMI-C00002" he="122.68mm" wi="73.91mm" file="US20180127406A1-20180510-C00002.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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INHIBITORS OF LYSINE SPECIFIC DEMETHYLASE-1 (Fri, 11 May 2018)
<p id="p-0001" num="0000">The present invention relates generally to compositions and methods for treating cancer and neoplastic disease. Provided herein are substituted heterocyclic derivative compounds and pharmaceutical compositions comprising said compounds. The subject compounds and compositions are useful for inhibition of lysine specific demethylase-1. Furthermore, the subject compounds and compositions are useful for the treatment of cancer, such as prostate cancer, breast cancer, bladder cancer, lung cancer and/or melanoma and the like.</p>
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EPOXYAZULENE DERIVATIVES USEFUL FOR TREATING CANCER AND DIABETES (Fri, 11 May 2018)
<p id="p-0001" num="0000">Disclosed is a compound of formula (I) in which R<sup>1</sup>-R<sup>5 </sup>and X<sup>1 </sup>are as described herein. Also provided are methods of using a compound of formula (I), including a method of treating cancer and a method of treating diabetes.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="36.07mm" wi="52.41mm" file="US20180127433A1-20180510-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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COMBINATIONS COMPRISING A PYRROLIDINE-2,5-DIONE IDO1 INHIBITOR AND AN ANTI-BODY (Fri, 11 May 2018)
<p id="p-0001" num="0000">Combinations of an IDO1 inhibitor (e.g., a 3-(5-fluoro-1H-indol-3-yl)pyrrolidine-2,5-dione compound), with an anti-PD1 antibody or anti-PD-L1 antibody, and an anti-4-1BB antibody, as selected anti-cancer or anti-viral agents are provided. Also provided are use of these combinations for the treatment and/or prevention of cancer and endometriosis.</p>
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THERAPEUTICALLY ACTIVE COMPOUNDS AND THEIR METHODS OF USE (Fri, 11 May 2018)
<p id="p-0001" num="0000">Provided are compounds useful for treating cancer and methods of treating cancer, for example an advanced solid tumor, such as a glioma, or angioimmunoblastic T-cell lymphoma (AITL).</p>
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SUBSTITUTED QUINAZOLINES FOR INHIBITING KINASE ACTIVITY (Fri, 11 May 2018)
<p id="p-0001" num="0000">Chemical entities that are kinase inhibitors, pharmaceutical compositions and methods of treatment of cancer are described.</p>
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CERTAIN CHEMICAL ENTITIES, COMPOSITIONS, AND METHODS (Fri, 11 May 2018)
<p id="p-0001" num="0000">Chemical entities that are bufalin derivatives, pharmaceutical compositions and methods of treatment of cancer are described.</p>
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MODIFIED BINDING PROTEINS INHIBITING THE VEGF-A RECEPTOR INTERACTION (Fri, 11 May 2018)
<p id="p-0001" num="0000">The present invention relates to binding proteins specific for VEGF-A, in particular to recombinant binding proteins comprising a polyethylene glycol moiety and a binding domain, which inhibits VEGF-Axxx binding to VEGFR-2. Examples of such recombinant binding proteins are proteins which comprise an ankyrin repeat domain with the desired binding specificity, and a polyethylene glycol moiety. The binding proteins are useful in the treatment of cancer and other pathological conditions, e.g. eye diseases such as age-related macular degeneration.</p>
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TRAIL RECEPTOR-BINDING AGENTS AND USES OF SAME (Fri, 11 May 2018)
<p id="p-0001" num="0000">The present invention discloses TRAIL receptor-binding agents, their therapeutic effects on tumor inhibition in vitro and in vivo, alone or in combination with various chemotherapeutic agents. In particular, the present invention discloses methods for the treatment of cancer, comprising administrating a TRAIL receptor binding agent of the present technology, alone or in combination with a chemotherapeutic agent.</p>
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ANTIBODY-VACCINE ENGINEERED CONSTRUCTS (AVEC) (Fri, 11 May 2018)
<p id="p-0001" num="0000">Hereby, we disclose and claim, the concept, designs, enabling technologies, and utility for therapy of patients suffering from cancer, of a novel class of biomolecularly engineered, synthetic molecules: antibody-vaccine engineered constructs (AVEC). They comprise the main functional domains (antibodies and vaccines) and the supporting domains (linkers and reporters). Their mechanisms of actions rely upon antibody dependent redirecting, accelerating, and amplifying of the prophylactic or natural vaccination induced immune response (ADRAAVIR) from the initially elicited by vaccination towards the finally aimed by therapies. The routes of administration to the patients, pharmacokinetics, pharmacodynamics, pharmacogenomics, and therapeutic efficacies are resultant of those of the pertinent antibodies and vaccines assembled within AVEC.</p>
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TREATMENT OF CANCER USING CHIMERIC ANTIGEN RECEPTORS (Fri, 11 May 2018)
<p id="p-0001" num="0000">The invention provides compositions and methods for treating diseases associated with expression of CD20 or CD22. The invention also relates to chimeric antigen receptor (CAR) specific to CD20 or CD22, vectors encoding the same, and recombinant T or natural killer (NK) cells comprising the CD20 CAR or CD22 CAR. The invention also includes methods of administering a genetically modified T cell or NK cell expressing a CAR that comprises a CD20 or CD22 binding domain.</p>
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COMPOSITIONS FOR TREATING CANCER AND METHODS FOR MAKING THE SAME (Fri, 11 May 2018)
<p id="p-0001" num="0000">Described herein are compositions and methods relating to chemotherapeutic agent conjugates and the treatment of cancer.</p>
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METHODS AND COMPOSITIONS FOR THERANOSTIC NANOPARTICLES (Fri, 11 May 2018)
<p id="p-0001" num="0000">Disclosed are compositions and methods for identifying a solid tumor cell target. Compositions and methods for treating prostate cancer are also disclosed. Further, cancer therapeutic compositions comprising CT20p are disclosed. Nanoparticles that are conjugated with a targeting ligand that is a substrate for a solid tumor-specific cell protein are disclosed.</p>
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DENDRI-TAC AND THEIR USE AS THERANOSTICS (Fri, 11 May 2018)
<p id="p-0001" num="0000">The present invention relates to novel amphiphilic dendrimers, hereafter denoted Dendri-TAC. The present invention also relates to perfluorocarbon nanoemulsions stabilized by these amphiphilic dendrimers and their uses for in vivo diagnostic and/or for therapy, notably as theranostic tools, for detection and/or treatment of cancer.</p>
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COMPOSITIONS FOR ENHANCING DELIVERY OF AGENTS ACROSS THE BLOOD BRAIN BARRIER AND METHODS OF USE THEREOF (Fri, 11 May 2018)
<p id="p-0001" num="0000">Compositions and methods for improved delivery of active agents to the brain are provided. The compositions typically include a nanocarrier, such as a polymeric nanoparticle, liposome, or nanolipagel or are in the form of a conjugate. The nanocarriers or conjugates typically include three components: a targeting moiety; a blood brain barrier blood-brain barrier modulator (BBB modulator), loaded into, attached to the surface of, and/or enclosed within a nanocarrier; and an additional active agent loaded into, attached to the surface of, and/or enclosed within a nanocarrier. The targeting moiety, which is typically conjugated to or otherwise dismodulator played on the surface of the nanocarrier, can be, for example, a moiety that preferentially or specifically targets brain cells or tissue, cancer cells, or a combination thereof.</p>
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C5, C6 SUBSTITUTED AND/OR FUSED OXINDOLES AS ANTI-CANCER AGENTS AND PROCESS FOR PREPARATION THEREOF (Fri, 11 May 2018)
<p id="p-0001" num="0000">The present invention describes the C5,C6 Substituted and/or fused oxindole compounds useful as anti-cancer agents and process for preparation thereof. Particularly the present invention relates to C5,C6 Substituted and/or fused oxindole compounds of formula I.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="34.88mm" wi="66.97mm" file="US20180127365A1-20180510-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">wherein, <ul id="ul0001" list-style="none"> <li id="ul0001-0001" num="0000"> <ul id="ul0002" list-style="none"> <li id="ul0002-0001" num="0000">A=C, CH, CH<sub>2</sub>, None</li> <li id="ul0002-0002" num="0000">B=C or CH part of open chain and/or cyclic alkyl/aryl/heteroaryl moiety</li> <li id="ul0002-0003" num="0000">G=alkyl, alkenyl, alkynyl, aryl, heteroaryl, heteroalkyl, alkoxy, aryloxy-all these optionally substituted with one or more substituents</li> <li id="ul0002-0004" num="0000">D=O, N, S, OH, SH, NH, None</li> <li id="ul0002-0005" num="0000">Z=C, CH<sub>2 </sub></li> <li id="ul0002-0006" num="0000">Ring E=aryl/heteroaryl/cycloalkyl optionally substituted with one or more substituents</li> <li id="ul0002-0007" num="0000">Ring C=aryl/heteroaryl/cycloalkyl optionally substituted with one or more substituents</li> <li id="ul0002-0008" num="0000">L=H, alkyl, alkoxy, halogen, CN, OH, amino, NO<sub>2 </sub></li> <li id="ul0002-0009" num="0000">K=H, alkyl, alkoxy, halogen, CN, OH, amino, NO<sub>2 </sub></li> <li id="ul0002-0010" num="0000">X=H, alkyl, alkoxy, halogen, CN, OH, amino, NO<sub>2 </sub></li> <li id="ul0002-0011" num="0000">Y=H, alkyl, alkoxy, halogen, CN, OH, amino, NO<sub>2 </sub></li> <li id="ul0002-0012" num="0000">R1=H, alkyl</li> <li id="ul0002-0013" num="0000">R2=H, alkyl, halogen, CN, NO<sub>2</sub>, alkoxy, amino, OH</li> </ul> </li> </ul> </p>
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LSD1 Inhibitors (Fri, 11 May 2018)
<p id="p-0001" num="0000">The present invention relates to compounds that inhibit LSD1 activity. In particular, the present invention relates to compounds, pharmaceutical compositions and methods of use, such as methods of treating cancer using the compounds and pharmaceutical compositions of the present invention.</p>
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IMIDAZOLYL TRICYCLIC ENONES AS ANTIOXIDANT INFLAMMATION MODULATORS (Fri, 11 May 2018)
<p id="p-0001" num="0000">Disclosed herein are compounds of the formula: (I), wherein the variables are defined herein. Also provided are pharmaceutical compositions thereof. In some aspects, the compounds and compositions provided herein may be used as antioxidant inflammation modulators. In some aspects, the present disclosure provides methods wherein the compounds and composition described herein are used for the treatment of diseases and disorders associated with inflammation and cancer.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="30.23mm" wi="57.74mm" file="US20180127380A1-20180510-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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TETRASUBSTITUTED ALKENE COMPOUNDS AND THEIR USE (Fri, 11 May 2018)
<p id="p-0001" num="0000">Disclosed herein are compounds, or pharmaceutically acceptable salts thereof, and methods of using the compounds for treating breast cancer by administration to a subject in need thereof a therapeutically effective amount of the compounds or pharmaceutically acceptable salts thereof. The breast cancer may be an ER-positive breast cancer and/or the subject in need of treatment may express a mutant ER-α protein.</p>
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NOVEL CLASS OF QUINOLONE HETEROCYCLIC AROMATIC MOLECULES FOR CANCER TREATMENT (Fri, 11 May 2018)
<p id="p-0001" num="0000">The invention is directed to new class of quinolone heterocyclic aromatic molecules (Renotinibs) and their use in the treatment of cancer, in particular, cancer that harbor abnormal human epidermal growth factor receptors (EGFRs).</p>
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INHIBITORS OF RAS AND METHODS OF USE THEREOF (Fri, 11 May 2018)
<p id="p-0001" num="0000">Compounds having activity as inhibitors of G12C mutant KRAS protein are provided. The compounds have the following structure (I):</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="17.44mm" wi="52.75mm" file="US20180127396A1-20180510-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">or a pharmaceutically acceptable salt, stereoisomer or prodrug thereof, wherein A, B, R″, Q, W, X, Y, Z, n<sup>2 </sup>and <img id="CUSTOM-CHARACTER-00001" he="3.56mm" wi="2.79mm" file="US20180127396A1-20180510-P00001.TIF" alt="custom-character" img-content="character" img-format="tif"/> are as defined herein. Methods associated with preparation and use of such compounds, pharmaceutical compositions comprising such compounds and methods to modulate the activity of G12C mutant KRAS protein for treatment of disorders, such as cancer, are also provided.</p>
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SUBSTITUTED PURINE COMPOUNDS (Fri, 11 May 2018)
<p id="p-0001" num="0000">The present invention relates to substituted purine compounds. The present invention also relates to pharmaceutical compositions containing these compounds and methods of treating disorders in which DOT1-mediated protein methylation plays a part, such as cancer, by administering these compounds and pharmaceutical compositions to subjects in need thereof.</p>
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5-SUBSTITUTED INDAZOLE-3-CARBOXAMIDES AND PREPARATION AND USE THEREOF (Fri, 11 May 2018)
<p id="p-0001" num="0000">Indazole compounds for treating various diseases and pathologies are disclosed. More particularly, the present disclosure concerns the use of an indazole compound or analogs thereof, in the treatment of disorders characterized by the activation of Wnt pathway signaling (e.g., cancer, abnormal cellular proliferation, angiogenesis, Alzheimer's disease, lung disease, fibrotic disorders, cartilage (chondral) defects, and osteoarthritis), the modulation of cellular events mediated by Wnt pathway signaling, and neurological conditions/disorders/diseases linked to overexpression of DYRK1A.</p>
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ECKOL DERIVATIVES, METHODS OF SYNTHESIS AND USES THEREOF (Fri, 11 May 2018)
<p id="p-0001" num="0000">Provided herein are eckol derivatives, methods of synthesis thereof and pharmaceutical compositions thereof. In other embodiments, provided herein are methods of treatment, prevention, or amelioration of a variety of medical disorders such as, for example, Alzheimer's disease, microbial infections, obesity, diabetes, cancer or inflammation using the compounds and pharmaceutical compositions disclosed herein.</p>
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SUBSTITUTED BENZIMIDAZOLES AND BENZOPYRAZOLES AS CCR(4) ANTAGONISTS (Fri, 11 May 2018)
<p id="p-0001" num="0000">Benzimidazole, benzopyrazole and benzotriazole compounds are provided which bind to CCR(4) and are useful for the treatment of diseases such as allergic diseases, autoimmune diseases, graft rejection and cancer.</p>
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ISOXAZOLYL SUBSTITUTED BENZIMIDAZOLES (Fri, 11 May 2018)
<p id="p-0001" num="0000">A compound which is a benzimidazolyl isoxazole of formula (I): wherein: R<sup>0 </sup>and R, which are the same or different, are each H or C<sub>1-6 </sub>alkyl; R<sup>9</sup>, R<sup>9 </sup>and R<sup>9</sup>, which are the same or different, are each H or F; X is -(alk<sub>n</sub>-, -alk-C(═O)—NR—, -alk-NR—C(═O)— or -alk-C(═O)—; R<sup>1 </sup>is selected from —S(═O)<sub>2</sub>R′; a 4- to 6-membered, C-linked heterocyclic group which is unsubstituted or substituted; and an N-linked spiro group of the following formula: R<sup>2 </sup>and R<sup>2′</sup>, which are the same or different, are each H or C<sub>1-6 </sub>alkyl, or R<sup>2 </sup>and R<sup>2′</sup> form, together with the C atom to which they are attached, a C<sub>3-6 </sub>cycloalkyl group; R<sup>3 </sup>and R<sup>3</sup>, which are the same or different, are each H, C<sub>1-6 </sub>alkyl, OH or F; R<sup>4 </sup>is phenyl or a 5- to 12-membered, N-containing heteroaryl group and is unsubstituted or substituted; alk is C<sub>1-6 </sub>alkylene; R′ is C<sub>1-6 </sub>alkyl; and n is 0 or 1; or a pharmaceutically acceptable salt thereof. The compound has activity in modulating the activity of p300 and/or CBP and is used to treat cancer, particularly prostate cancer.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="37.08mm" wi="63.58mm" file="US20180127402A1-20180510-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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PYRAZOLYL QUINOXALINE KINASE INHIBITORS (Fri, 11 May 2018)
<p id="p-0001" num="0000">The invention relates to new quinoxaline derivative compounds, to pharmaceutical compositions comprising said compounds, to processes for the preparation of said compounds and to the use of said compounds in the treatment of diseases, e.g. cancer.</p>
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Algorithms for Disease Diagnostics (Fri, 11 May 2018)
<p id="p-0001" num="0000">The present invention relates to compositions and methods for molecular profiling and diagnostics for genetic disorders and cancer, including but not limited to gene expression product markers associated with cancer or genetic disorders. In particular, the present invention provides algorithms and methods of classifying cancer, for example, thyroid cancer, methods of determining molecular profiles, and methods of analyzing results to provide a diagnosis.</p>
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METHODS FOR INCREASING EFFICACY OF FOLR1 CANCER THERAPY (Thu, 10 May 2018)
Methods to improve the success of cancer therapies that target the human folate receptor 1 are provided. Kits comprising reagent useful in the methods are further provided.
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BICYCLIC HETEROCYCLES AS FGFR INHIBITORS (Thu, 10 May 2018)
The present invention relates to bicyclic heterocycles of formula I, and pharmaceutical compositions of the same, that are inhibitors of one or more FGFR enzymes and are useful in the treatment of FGFR-associated diseases such as cancer.
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Anthracene-9, 10-dione dioxime compound prodrugs and their uses (Wed, 09 May 2018)
<p id="p-0001" num="0000">Chemical agents, such as disulfonamide derivatives of fluorene, anthracene, xanthene, dibenzosuberone and acridine, and similar heterocyclic ring structures; including, salts thereof that act as anti-cancer and anti-tumor agents, along with methods for preparing such agents, as well as pharmaceutical compositions containing such agents as active ingredients and methods of using these as therapeutic agents.</p>
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SELECTIVE ANDROGEN RECEPTOR DEGRADER (SARD) LIGANDS AND METHODS OF USE THEREOF (Fri, 04 May 2018)
<p id="p-0001" num="0000">This invention provides novel 3-amino propanamide selective androgen receptor degrader (SARD) compounds, pharmaceutical compositions and uses thereof in treating prostate cancer, advanced prostate cancer, castration resistant prostate cancer, androgenic alopecia or other hyperandrogenic dermal diseases, Kennedy's disease, amyotrophic lateral sclerosis (ALS), and uterine fibroids, and to methods for reducing the levels of androgen receptor-full length (AR-FL) including pathogenic or resistance mutations, AR-splice variants (AR-SV), and pathogenic polyglutamine (polyQ) polymorphisms of AR in a subject.</p>
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THERAPEUTIC AGENTS (Fri, 04 May 2018)
<p id="p-0001" num="0000">A compound of formula (I) or a compound of formula (II) or pharmaceutically acceptable salts thereof, wherein R1-R7 and X are as defined in the description, and the use of these compounds in therapy, in particular in treating cancer or as an inhibitor of the interaction of the MDM2 protein with p53.</p>
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HETEROCYCLIC DERIVATIVES MODULATING ACTIVITY OF CERTAIN PROTEIN KINASES (Fri, 04 May 2018)
<p id="p-0001" num="0000">The present invention relates to novel heterocyclic derivatives having general formula (I) and their therapeutic use for diseases such as cancer, inflammation, pain, autoimmune diseases or neurodegenerative diseases like Alzheimer's or Parkinson's disease that can be treated by modulation of certain protein kinases. Compounds of formula (I) can be used for treatment of patients who do not respond to kinase inhibition therapy that comprises currently available medications.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="27.86mm" wi="59.86mm" file="US20180118691A1-20180503-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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COMPOUNDS FOR TREATMENT OF CANCER (Fri, 04 May 2018)
<p id="p-0001" num="0000">The present invention relates to colchicine-binding site compounds having anti-cancer activity, compositions comprising the same, and their use for treating various forms of cancer.</p>
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SELECTIVE HDAC6 INHIBITORS (Fri, 04 May 2018)
<p id="p-0001" num="0000">The present invention provides a compound having the structure:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="11.51mm" wi="34.63mm" file="US20180118709A1-20180503-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <ul id="ul0001" list-style="none"> <li id="ul0001-0001" num="0000"> <ul id="ul0002" list-style="none"> <li id="ul0002-0001" num="0000">wherein</li> <li id="ul0002-0002" num="0000">R<sub>1 </sub>is halogen, —NR<sub>5</sub>R<sub>6</sub>, —NR<sub>5</sub>—C(═O)—R<sub>6</sub>, —NH—C(═O)—OR<sub>7</sub>, —OR<sub>7</sub>, —NO<sub>2</sub>, —CN, —SR<sub>7</sub>, —SO<sub>2</sub>R<sub>7</sub>, —CO<sub>2</sub>R<sub>7</sub>, CF<sub>3</sub>, —SOR<sub>7</sub>, —POR<sub>7</sub>, —C(═S)R<sub>7</sub>, —C(═O)—NR<sub>5</sub>R<sub>6</sub>, —CH<sub>2</sub>—C(═O)—NR<sub>5</sub>R<sub>6</sub>, —C(═NR<sub>5</sub>)R<sub>6</sub>, —P(═O)(OR<sub>5</sub>)(OR<sub>6</sub>), —P(OR<sub>5</sub>)(OR<sub>6</sub>), —C(═S)R<sub>7</sub>, C<sub>1-5 </sub>alkyl, C<sub>2-5 </sub>alkenyl, C<sub>2-5 </sub>alkynyl, aryl, heteroaryl, or heterocyclyl, <ul id="ul0003" list-style="none"> <li id="ul0003-0001" num="0000">wherein R<sub>5</sub>, R<sub>6</sub>, and R<sub>7 </sub>and are each, independently, H, C<sub>1-5 </sub>alkyl, C<sub>2-5 </sub>alkenyl, C<sub>2-5 </sub>alkynyl, heteroalkyl, hydroxyalkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C<sub>1-5 </sub>alkyl-aryl, or C<sub>1-5 </sub>alkyl-NH-aryl;</li> </ul> </li> <li id="ul0002-0003" num="0000">Ar<sub>1 </sub>is phenyl or thiophene;</li> <li id="ul0002-0004" num="0000">wherein when Ar<sub>1 </sub>is phenyl, then R<sub>1 </sub>is other than —C(═O)—NR<sub>5</sub>R<sub>6</sub>, where one of R<sub>5 </sub>or R<sub>6 </sub>is phenyl or quinoline and the other of R<sub>5 </sub>or R<sub>6 </sub>is hydroxyalkyl, or where one of R<sub>5 </sub>or R<sub>6 </sub>is quinoline and the other of R<sub>5 </sub>or R<sub>6 </sub>is H; and</li> <li id="ul0002-0005" num="0000">wherein when Ar<sub>1 </sub>is phenyl, then R<sub>1 </sub>is other than —NR<sub>5</sub>—C(═O)—R<sub>6</sub>, where one of R<sub>5 </sub>is H and R<sub>6 </sub>is quinoline, <br/> or a pharmaceutically acceptable salt thereof. </li> </ul> </li> </ul> </p>
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HISTONE DEMETHYLASE INHIBITORS (Fri, 04 May 2018)
<p id="p-0001" num="0000">The present invention relates generally to compositions and methods for treating cancer and neoplastic diseases. Provided herein are substituted imidazole-pyridine derivative compounds and pharmaceutical compositions comprising said compounds. The subject compounds and compositions are useful for inhibition of histone demethylase enzymes. Furthermore, the subject compounds and compositions are useful for the treatment of cancer, such as pancreatic cancer, prostate cancer, breast cancer, bladder cancer, lung cancer, gastric cancer, leukemia and/or melanoma and the like.</p>
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PYRIMIDINE DERIVATIVES (Fri, 04 May 2018)
<p id="p-0001" num="0000">Compounds of Formula I or II</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="49.78mm" wi="69.85mm" file="US20180118721A1-20180503-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">in which R1, X1 and X2 have the meanings indicated in claim <b>1</b>, are MTH1 inhibitors and can be employed, inter alia, in the treatment of cancer.</p>
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IDO Inhibitors (Fri, 04 May 2018)
<p id="p-0001" num="0000">Presently provided are IDO inhibitors and pharmaceutical compositions thereof, useful for modulating an activity of indoleamine 2,3-dioxygenase; treating indoleamine 2,3-dioxygenase (IDO) mediated immunosuppression; treating a medical conditions that benefit from the inhibition of enzymatic activity of indoleamine-2,3-dioxygenase; enhancing the effectiveness of an anti-cancer treatment comprising administering an anti-cancer agent; treating tumor-specific immunosuppression associated with cancer; and treating immunosupression associated with an infectious disease.</p>
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SUBSTITUTED QUINAZOLINES AS INHIBITORS OF KRAS G12C (Fri, 04 May 2018)
<p id="p-0001" num="0000">Compounds having activity as inhibitors of G12C mutant KRAS protein are provided. The compounds have the following structure (I):</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="24.72mm" wi="65.02mm" file="US20180118757A1-20180503-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">or a pharmaceutically acceptable salt, tautomer, prodrug or stereoisomer thereof, wherein R<sup>1</sup>, R<sup>2a</sup>, R<sup>3a</sup>, R<sup>3b</sup>, R<sup>4a</sup>, R<sup>4b</sup>, G<sup>1</sup>, G<sup>2</sup>, L<sup>1</sup>, L<sup>2</sup>, m<sup>1</sup>, m<sup>2</sup>, A, B, W, X, Y, Z and E are as defined herein. Methods associated with preparation and use of such compounds, pharmaceutical compositions comprising such compounds and methods to modulate the activity of G12C mutant KRAS protein for treatment of disorders, such as cancer, are also provided.</p>
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COMPOSITIONS AND METHODS FOR ALTERING SECOND MESSENGER SIGNALING (Fri, 04 May 2018)
<p id="p-0001" num="0000">The invention relates to compositions, methods, kits, and assays related to the use and/or exploitation of isomers of cGAMP as well as the structure of the enzyme cGAS.</p>
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MODULATORS OF FARNESOID X RECEPTOR AND METHODS FOR THE USE THEREOF (Fri, 04 May 2018)
<p id="p-0001" num="0000">Compounds, compositions and methods are provided for treating the FXR-mediated disease or process in a mammal, comprising administering to the mammal a therapeutically effective amount of a compound claimed, wherein the FXR-mediated disease or condition linked to chronic liver diseases such as nonalcoholic fatty liver disease and nonalcoholic steatohepatitis; gastrointestinal diseases; cardiovascular diseases; metabolic diseases such as diabetes and obesity; inflammation, or cancer etc.</p>
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DEMETHYLPENCLOMEDINE ANALOGS AND THEIR USE AS ANTI-CANCER AGENTS (Fri, 04 May 2018)
<p id="p-0001" num="0000">This disclosure concerns novel demethylpenclomedine analogs. Also disclosed are pharmaceutical compositions and methods for using such compositions to treat hyperproliferative disorders. In one embodiment the analogs are represented by the formula</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="24.98mm" wi="27.94mm" file="US20180117022A1-20180503-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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BROMODOMAIN AND EXTRA-TERMINAL PROTEIN INHIBITOR COMBINATION THERAPY (Fri, 04 May 2018)
<p id="p-0001" num="0000">The present disclosure relates generally to compositions and methods of treating neoplastic diseases or cancers, such as glioblastoma and non-Hodgkin's lymphomas, or other cancers in which the subject suffers from an advanced solid tumor, comprising a combination of, or administering a combination of, a bromodomain and extra-terminal protein (BET) inhibitor and at least one chemotherapeutic agent, which does not inhibit BET directly. The BET inhibitor/chemotherapeutic agent combination, or combination therapy, can yield synergistic effects, thereby increasing the effectiveness of the cancer treatment as compared with the administration of either the BET inhibitor or the chemotherapeutic agent alone.</p>
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6-AMINO-PURIN-8-ONE COMPOUNDS (Fri, 04 May 2018)
<p id="p-0001" num="0000">Compounds of formula (I):</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="37.34mm" wi="69.85mm" file="US20180117048A1-20180503-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">wherein R<sup>1 </sup>is C<sub>1-6</sub>alkylamino, C<sub>1-6</sub>alkoxy, or C<sub>3-7</sub>cycloalkyloxy; m is an integer having a value of 3 to 6; n is an integer having a value of 0 to 4; and salts thereof are inducers of human interferon. Compounds which induce human interferon may be useful in the treatment of various disorders, for example the treatment of allergic diseases and other inflammatory conditions for example allergic rhinitis and asthma, the treatment of infectious diseases and cancer, and may also be useful as vaccine adjuvants.</p>
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DEUTERIUM-ENRICHED ISOINDOLINONYL-PIPERIDINONYL CONJUGATES AND OXOQUINAZOLIN-3(4H)-YL-PIPERIDINONYL CONJUGATES AND METHODS OF TREATING MEDICAL DISORDERS USING SAME (Fri, 04 May 2018)
<p id="p-0001" num="0000">The invention provides deuterium-enriched isoindolinonyl-piperidinonyl conjugates, deuterium-enriched oxoquinazolin-3(4H)-yl-piperidinonyl conjugates, pharmaceutical compositions, and methods of using such conjugates and pharmaceutical compositions to treat cancer, angiogenesis disorders, immune disorders, and other medical disorders.</p>
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Binding Agents That Modulate the Hippo Pathway and Uses Thereof (Fri, 04 May 2018)
<p id="p-0001" num="0000">The present invention relates to agents that modulate the Hippo pathway and Hippo pathway signaling, such as antibodies and soluble receptors, as well as to methods of using the agents for the treatment of diseases such as cancer.</p>
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ANTIBODIES SPECIFIC TO GLYCOSYLATED PD-L1 AND METHODS OF USE THEREOF (Fri, 04 May 2018)
<p id="p-0001" num="0000">Antibodies that bind specifically to glycosylated PD-L1 relative to unglycosylated PD-L1 are provided. Antibodies that recognize specific epitopes of glycosylated PD-L1 protein and can block the binding of PD-L1 to PD-1 are provided. In some aspects, PD-L1 polypeptides comprising glycosylated amino acid residues at amino and carboxy terminal positions of the PD-L1 extracellular domain are also provided. Methods for making and using such antibodies and polypeptides (e.g., for the treatment of cancer) are also provided.</p>
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CAR T-CELLS FOR THE TREATMENT OF B7-H4 EXPRESSING SOLID TUMORS (Fri, 04 May 2018)
<p id="p-0001" num="0000">CAR cells and antibodies targeting human B7-H4 expressed on many human cancers including but not limited to breast ovarian, and renal cancers are described as a new method of cancer treatment. It is proposed that B7-H4 CAR cells are safe and effective in patients and can be used to treat human tumors expressing the B7-H4 surface protein.</p>
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SHMT Inhibitors (Fri, 04 May 2018)
<p id="p-0001" num="0000">The present invention relates to a method for the treatment of cancer or an autoimmune disorder, comprising the administration of a serine hydroxymethyltransferase (SHMT) inhibitor, and in particular the administration of pyrazolopyran compounds of Formula (VI) as presently described, wherein the compounds are capable of inhibiting a mammalian SHMT, such as human SHMT1 and/or SHMT2. The treatment method further comprises the optional administration of an additional agent as a rescue therapy to reduce toxicity, wherein said agent may be chosen from formate, a formate salt, folinic acid, formate ester, or leucovorin.</p>
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COMBRETASTATIN ANALOGS (Fri, 04 May 2018)
<p id="p-0001" num="0000">The present invention relates novel heterocyclic analogs of combretastatin, their synthesis, and their use as anti-cancer compounds. In particular, compounds of Formula (I), Formula (II), and Formula (V) are provided.</p>
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Substituted Quinazoline Derivatives as DNA Methyltransferase Inhibitors (Fri, 04 May 2018)
<p id="p-0001" num="0000">The present invention relates to compounds of the following formula (I) and pharmaceutically acceptable salts and solvates thereof, their methods of preparation, their use as a drug, notably in the treatment of cancer, and pharmaceutical compositions containing such compounds.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="22.10mm" wi="69.85mm" file="US20180118717A1-20180503-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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NOVEL ARYL-CYANOGUANIDINE COMPOUNDS (Fri, 04 May 2018)
<p id="p-0001" num="0000">The present invention relates to protein-lysine N-methyltransferase SMYD2 (SET and MYND domain-containing protein 2) inhibitors, in particular SMYD2-inhibitory substituted cyanoguanidine-pyrazolines of general formula (I), wherein R<sup>1</sup>, R<sup>3</sup>, R<sup>4</sup>, R<sup>5 </sup>and n have the meaning as described and defined herein, as well as to pharmaceutical compositions comprising compounds according to the invention and to their prophylactic and therapeutic use for hyperproliferative disorders, in particular for cancer, respectively tumour disorders. The present invention furthermore relates to the use of SMYD2 inhibitors for benign hyperplasias, atherosclerotic disorders, sepsis, autoimmune disorders, vascular disorders, viral infections, neurodegenerative disorders, inflammatory disorders, atherosclerotic disorders and the control of male fertility.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="53.09mm" wi="68.07mm" file="US20180118722A1-20180503-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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PHARMACOLOGICALLY ACTIVE COMPOUNDS (Fri, 04 May 2018)
<p id="p-0001" num="0000">The present invention relates to compounds of formula II</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="35.73mm" wi="69.85mm" file="US20180117032A1-20180503-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">wherein X, Y, R<sub>2</sub>, R<sub>3</sub>, R<sub>4 </sub>and Ar are all as defined herein. The compounds of the present invention are known to inhibit the spindle checkpoint function of Monospindle 1 (Mps1—also known as TTK) kinases either directly or indirectly via interaction with the Mps1 kinase itself. In particular, the present invention relates to the use of these compounds as therapeutic agents for the treatment and/or prevention of proliferative diseases, such as cancer. The present invention also relates to processes for the preparation of these compounds, and to pharmaceutical compositions comprising them.</p>
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Method of using dihydro-resveratrol or its stilbenoid derivatives and/or chemical variants in treatment of tumorous pathologies (Fri, 04 May 2018)
<p id="p-0001" num="0000">The present invention relates to a polyphenol derivative of the stilbenoid family, namely trans-3,5,4′-trihydroxybibenzyl, also known as dihydro-resveratrol, as a remedial agent. In particular, the present invention presents the usage of dihydro-resveratrol or its derivatives/chemical variants in the manufacture of a medicament for the treatment of tumors or cancers. The dihydrostilbenes can be used in the treatment or delay of progression of a cancer in a patient or used in a pharmaceutical formulation for the aforementioned purposes.</p>
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6,7,8,9-TETRAHYDRO-3H-PYRAZOLO[4,3-F]ISOQUINOLINE DERIVATIVES USEFUL IN THE TREATMENT OF CANCER (Fri, 04 May 2018)
The specification relates to compounds of Formula (I) and to pharmaceutically acceptable salts thereof, to processes and intermediates used for their preparation, to pharmaceutical compositions containing them and to their use in the treatment of cell proliferative disorders.
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MODULATORS OF HEDGEHOG (HH) SIGNALLING PATHWAY (Fri, 04 May 2018)
There are described compounds of formula (I): and there use as a medicament in the treatment of conditions involving abnormal activation and/or malfunction of the of the hedgehog pathway, such as cancer, fibrosis and chronic graft-versus-host disease (cGVHD).
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HYPERPOLARIZED [3- 13C]ACETOACETATE AND METHODS OF USING THE SAME (Fri, 04 May 2018)
The present invention relates to hyperpolarized [3-13C]acetoacetate. Provided are [3-13C]acetoacetate and compositions comprising said [3-13C]acetoacetate. Further provided are methods of preparing and using hyperpolarized [3- 13C]acetoacetate in the determination of the spatial and temporal distribution and metabolism of [3-13C]acetoacetate and/or its metabolites in a cell or subject, preferably by magnetic resonance imaging (MRI), magnetic resonance spectroscopy (MRS), and/or magnetic resonance spectroscopic imaging (MRSI), whereby conditions, diseases, or disorders associated with the metabolism of acetoacetate and/or other ketone bodies can be diagnosed. The conditions, diseases, or disorders to be diagnosed preferably are cancer, diabetes, cardiovascular diseases, or neurodegenerative diseases.
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DEUTERATED N-(5-((4-ETHYLPIPERAZIN-1-YL)METHYL) PYRIDIN-2-YL)-5-FLUORO-4-(4-FLUORO-1-ISOPROPYL-2-METHYL-1H-BENZO[d]IMIDAZOL-6-YL)PYRIMIDIN-2-AMINE (Fri, 04 May 2018)
The present invention is related to compounds of Formula (I): (I) or a pharmaceutically acceptable salt thereof; wherein: Y1, Y2, Y3, Y4, Y4,, Y5, Y5,, Y6,Y6,, Y7, Y7,,Υ8, Y8', Y9, Y9', Y10, Y10', YI0", Y11, Y12, Y13, Y14, Y I4', Y14", Υ15, Y16, Υ16', Y16", Y17, Y17' and Y17" are selected from the group consisting of hydrogen or deuterium, wherein at least one of Y1, Y2, Y3, Y4, Y4,,Y5 Y5,, Y6, Y6,, Y7, Y7,, Y8, Y8', Y9, Y9', Y10, Y10', Y10", Υ11, Y12, Y13, Y14, Y14', Y14", Y15, Y16, Y16', Y16", Y17, Y17', and Y17'' is deuterium; and each carbon is independently optionally replaced with 13C. It also relates to pharmaceutical compositions comprising the compounds of Formula (I) and the use of these compounds as selective CDK4/6 inhibitors with the potential for treatment of pRb-positive tumor types including HR (hormone-receptor)-positive aid HER2 (human epidermal growth factor receptor 2)- negative breast cancer, melanoma, liposarcoma and non-small-cell lung cancer, alone or in combination with additional agents.
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DEUTERATED 7-CYCLOPENTYL-N, N-DIMETHYL-2-((5-(PIPERAZIN-1-YL)PYRIDIN-2-YL)AMINO)-7H-PYRROLO[2,3-D]PYRIMDINE-6-CARBOXAMIDE (Fri, 04 May 2018)
The present invention is related to compounds of Formula (I): (I) or a pharmaceutically acceptable salt thereof; wherein: Y1, Y2, Y3, Y4, Y4,, Y5, Y5,; Y6, Y6,, Y7, Y7,, Y8, Y9, Y10, Y10,, Y10,,, Y11, Y11,, Y11,,, Y12, Y12,, Y13, Y13,, Y14, Y14,, Y15, Y15, and Y16 are selected from the group consisting of hydrogen or deuterium, wherein at least one of Y1, Y2, Y3, Y4, Y4,, Y5, Y5,; Y6, Y6,, Y7, Y7,, Y8, Y9, Y10, Y10,, Y10,,, Y11, Y11,, Y11,,, Y12, Y12,, Y13, Y13,, Y14, Y14,, Y15, Y15, and Y16 is deuterium; and each carbon is independently optionally replaced with l3C. It also relates to pharmaceutical compositions comprising the compounds of Formula (I) and the use of these compounds as selective CDK4/6 inhibitors with the potential for treatment of pRb-positive tumor types including HR-positive and HER2 -negative breast cancer in combination with additional agents (i.e. letrozole).
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METHODS OF TREATMENT FOR MYELOID LEUKEMIA (Fri, 04 May 2018)
Embodiments of the present disclosure provide for methods of treating cancer (e.g., leukemia), pharmaceutical compositions for treating cancer, methods of modulating cancer progression and development, and the like.
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POLYOXOMETALATE COMPLEXES AND USES IN MANAGING CANCER (Fri, 04 May 2018)
The disclosure relates polyoxometalate complexes and uses in the management, treatment, or prevention of cancer. In certain embodiments, the polyoxometalate complexes comprise polydentate oxygen bridging ligands such as those of the following formula: [POM{(OCH2)3CX}2], [M6O13{(OCH2)3CX}2], [V6O13{(OCH2)3CX}2], salts, or derivatives thereof wherein POM is a polyoxometalate, M is a metal, and X is defined herein. In certain embodiments, the disclosure relates to pharmaceutical compositions comprising polyoxometalate complexes disclosed herein.
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BROMODOMAIN AND EXTRA-TERMINAL PROTEIN INHIBITOR COMBINATION THERAPY (Fri, 04 May 2018)
The present disclosure relates generally to compositions and methods of treating neoplastic diseases or cancers, such as glioblastoma and non-Hodgkin's lymphomas, or other cancers in which the subject suffers from an advance solid tumor, comprising a combination of, or administering a combination of, a bromodomain and extra-terminal protein BET inhibitor and at least on echemotherapeutic agent, which does not inhibit BET directly. The BET inhibitor/chemotherapeutic agent combination, or combination therapy, can yield syngergistic effects, thereby increasing the effectiveness of the cancer treatment as compared with the administration of either the BET inhibitor or the chemotherapeutic agent alone.
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COMPOSITIONS AND METHODS FOR TREATING EZH2-MEDIATED CANCER (Fri, 04 May 2018)
Methods for designing bivalent compounds which selectively degrade/disrupt EZH2 and compositions and methods of using such degraders/disruptors to treat EZH2-mediated cancer are provided.
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