METABOLOMIC PROFILING DEFINES ONCOGENES DRIVING PROSTATE TUMORS (Fri, 13 Jun 2014)
The invention provides methods and products to identify metabolic status of Aktl and Myc in tumors, and to treat cancer. The method comprises performing an assay to measure a profile of metabolites in a prostate tumor sample obtained from a subject, wherein the metabolites are differentially produced in prostate tumors with high Aktl expression versus prostate tumors with high Myc expression; and comparing, with at least one processor, the profile of metabolites with an appropriate reference profile of the metabolites to assign an Aktl and Myc metabolic status to the sample based on results of the comparison.
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BRAF Mutations Conferring Resistance to BRAF Inhibitors (Fri, 06 Jun 2014)
<p id="p-0001" num="0000">The present invention relates to methods, compositions and kits concerning resistance to treatment with an anti-cancer agent, specifically an inhibitor of BRAF. In particular embodiments, the invention concerns mutations in a BRAF sequence that confer resistance to a BRAF inhibitor. Identification of such mutations in a BRAF sequence allows the identification and design of second-generation BRAF inhibitors. Methods and kits for detecting the presence of a mutant BRAF sequence in a sample are also provided.</p>
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PYRROL-1 -YL BENZOIC ACID DERIVATES USEFUL AS MYC INHIBITORS (Fri, 09 May 2014)
The present invention provides compounds of Formula (I-A), (I-B), and (I-C), pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof. Compounds of the present invention are useful for inhibiting Myc (e.g., c-Myc) activity. The present invention further provides methods of using the compounds described herein for treating Myc-mediated disorders (e.g., cancer and other proliferative diseases). The present invention also provides assays for identifying Myc inhibitors.
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Muc-1 cytoplasmic domain peptides as inhibitors of cancer (Thu, 08 May 2014)
The invention provides for peptides from the MUC1 cytoplasmic domain and methods of use therefor. These peptides can inhibit MUC1 oligomerization, thereby preventing tumor cell growth, inducing tumor cell apoptosis and necrosis of tumor tissue in vivo.
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TARGETING DEREGULATED WNT SIGNALING IN CANCER USING STABILIZED ALPHA-HELICES OF BCL-9 (Fri, 25 Apr 2014)
<p id="p-0001" num="0000">The invention provides structurally-constrained peptides by hydrocarbon stapling of a BCL9 HD2 helix for use as a therapeutic agent. The invention further provides methods and kits for use of the structurally-constrained peptide of the instant invention. The invention is based, at least in part, on the results provided herein demonstrating that hydrocarbon stapled helical peptides display excellent proteolytic, acid, and thermal stability, restore the native helical structure of the peptide, possess superior pharmacokinetic properties compared to the corresponding unmodified peptides, and are highly effective in binding to β-catenin in vitro, in cellulo, and in vivo, disrupting the BCL-9/β-catenin interaction, and thereby interfering with deregulated Wnt/β-catenin signaling for therapeutic benefit in a variety of human diseases including human cancer.</p>
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INHIBITORS OF CYCLIN-DEPENDENT KINASE 7 (CDK7) (Fri, 25 Apr 2014)
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., leukemia, lymphoma, melanoma, multiple myeloma, breast cancer, Ewing's sarcoma, osteosarcoma, brain cancer, neuroblastoma, lung cancer), 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, such as cyclin-dependent kinase (CDK) (e.g., cyclin-dependent kinase 7 (CDK7)), and therefore, induce cellular apoptosis and/or inhibit transcription in the subject.
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HYDROPHOBICALLY TAGGED SMALL MOLECULES AS INDUCERS OF PROTEIN DEGRADATION (Fri, 25 Apr 2014)
Provided are bifunctional small molecules of Formula (I): or pharmaceutically acceptable salts thereof, wherein M represents a small organic molecule which binds, covalently or non-covalently, a kinase, such as Her3 protein kinase; L1 represents a linker; and RH represents a hydrophobic group. An example of a compound of Formula (I) is a compound of Formula (II): Also provided are pharmaceutical compositions comprising a compound of Formula (I) or (II) and methods of using such compounds for treating proliferative diseases.
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HISTONE DEACETYLASE INHIBITORS AND METHODS OF USE THEREOF (Fri, 18 Apr 2014)
<p id="p-0001" num="0000">The present invention provides novel compounds for inhibiting histone deacetylases, and pharmaceutically acceptable salts and derivatives thereof. The present invention further provides methods for treating disorders regulated by histone deacetylase activity (e.g., proliferative diseases, cancer, inflammatory diseases, protozoal infections, hair loss, etc.) comprising administering a therapeutically effective amount of a compound of the invention to a subject in need thereof. The present invention also provides methods for preparing compounds of the invention.</p>
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GSK3 INHIBITORS AND METHODS OF USE THEREOF (Fri, 18 Apr 2014)
The present invention provides compounds of formula I, pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof. Compounds of the present invention are useful for inhibiting kinase (e.g., GSK3 (e.g., GSK3a or GSK3P) or CK1) activity. The present invention further provides methods of using the compounds described herein for treating kinase-mediated disorders, such as neurological diseases, psychriatic disorders, metabolic disorders, and cancer. I
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Method for Preparing Largazole Analogs and Uses Thereof (Fri, 04 Apr 2014)
<p id="p-0001" num="0000">Analogs of largazole are described herein. Methods of treating cancer and blood disorders using largazole and largazole analogs and pharmaceutical compositions comprising the same are additionally described herein. Methods for preparing largazole analogs are likewise described.</p>
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COMPOSITIONS AND METHODS FOR INCREASING ERYTHROPOIETIN (EPO) PRODUCTION (Fri, 24 Jan 2014)
<p id="p-0001" num="0000">The invention relates to double-stranded ribonucleic acid (dsRNA) compositions targeting one or more EGLN genes, EGLN1, EGLN2 and/or EGLN3 and methods of using such dsRNA compositions to inhibit expression of these genes.</p>
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Compositions and Methods for Treating Leukemia (Fri, 10 Jan 2014)
<p id="p-0001" num="0000">The invention provides compositions, methods, and kits for the treatment of acute myeloid leukemia in a subject.</p>
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DEACETYLASE INHIBITORS AND USES THEREOF (Fri, 13 Dec 2013)
<p id="p-0001" num="0000">The present invention provides novel compounds of formula (I) and pharmaceutical compositions thereof. The inventive compounds are useful as deacetylase inhibitors (e.g., histone deacetylase inhibitors) and may be useful in the treatment of proliferative diseases such as cancer. In particular, the inventive compounds are HDAC6 inhibitors. The invention also provide synthetic methods for preparing the inventive compounds.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="37.42mm" wi="70.53mm" file="US20130331455A1-20131212-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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Signatures and Determinants Associated with Cancer and Methods of Use Thereof (Fri, 06 Dec 2013)
<p id="p-0001" num="0000">The present invention provides methods of detecting cancer using biomarkers.</p>
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TARGETING THE GLUTAMINE TO PYRUVATE PATHWAY FOR TREATMENT OF ONCOGENIC KRAS-ASSOCIATED CANCER (Fri, 29 Nov 2013)
Methods and kits for GPP-targeting, e.g., for the treatment of oncogenic Kras-associated cancers, and methods for determining the efficacy of those methods are provided.
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MUC1 AND GALECTIN-3 (Fri, 18 Oct 2013)
<p id="p-0001" num="0000">The invention provides methods of identifying and making compounds that inhibit the interaction between MUC1 and galectin-3. Also embraced by the invention are in vivo and in vitro methods of inhibiting such an interaction and of inhibiting the expression of galectin-3 by a cell.</p>
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TRPV4 ANTAGONIST AND METHODS OF USE THEREOF (Fri, 11 Oct 2013)
Methods of treating or preventing disorders using compounds that regulate TRPV 4 pathway are described. Methods and cells that can be used to evaluate compounds, such as TRPV 4 antagonists, for treatment or prevention disorders are also provided. In some embodiments, the TRPV 4 antagonist is selected, at least in part, on the basis that it is a TRPV 4 antagonist. In some embodiments, the TRPV 4 antagonist does not inhibit one, two, or all of TRPV1, TRPV2, and TRPV3. In some embodiments, the TRPV4 antagonist inhibits one, two, or all of TRPV1, TRPV2, and TRPV3. In some embodiments, the TRPV 4 antagonist is selected from the group consisting of rimonabant, AMG-251, AMG9810, GSK205, and BCTC.
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SMALL MOLECULE PRINTING (Fri, 04 Oct 2013)
<p id="p-0001" num="0000">The present invention provides compositions and methods to facilitate the identification of compounds that are capable of interacting with a biological macromolecule of interest. In one aspect, a composition is provided that comprises an array of one or more types of chemical compounds attached to a solid support using isocyanate or isothiocyanate chemistry, wherein the density of the array of compounds is at least 1000 spots per cm<sup>2</sup>. In general, these inventive arrays are generated by: (1) providing a solid support, wherein said solid support is functionalized with an isocyanate or isothiocyanate moiety capable of interacting with a desired chemical compound to form a covalent attachment; (2) providing one or more solutions of one or more types of compounds to be attached to the solid support; (3) delivering said one or more types of compounds to the solid support; and (4) catalyzing the attachment of the compound to the solid support, whereby an array is formed and the array of compounds has a density of at least 1000 spots per cm<sup>2</sup>. In another aspect, the present invention provides methods for utilizing these arrays to identify small molecule partners for biological macromolecules of interest.</p>
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COMPOSITIONS, KITS, AND METHODS FOR THE GENERATION OF IMMUNOGLOBULIN SEQUENCES (Fri, 04 Oct 2013)
The present invention is based, in part, on the discovery of certain oligonucleotide sequences derived from specific regions of the rhesus monkey (Macaca mulatta) immunoglobulin gene repertoire sequences useful for amplifying the light chain, heavy chain, and full-length immunoglobulin genes encoding the entire Macaca mulatta immunoglobulin gene repertoire. Thus, the present invention allows for the generation of diverse and complex libraries of Macaca mulatta immunoglobulin gene sequences encoding full-length immunoglobulins, as well as fragments and variants thereof (e.g., scFvs).
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INHIBITION OF MCL-1 AND/OR BFL-1/A1 (Fri, 27 Sep 2013)
This disclosure features compounds and pharmaceutically acceptable salts thereof that inhibit MCL-1 and/or BFL-1/A1 and compositions containing the same. This disclosure also features combinations that include one or more of the MCL-1/BFL-1/A1 inhibitor compounds described herein, or a pharmaceutically acceptable salt thereof; and one or more additional therapeutic agents (e.g., one or more chemotherapeutic agents (including small molecule and/or anti-body based chemotherapy and/or radiation); e.g., one or more therapeutic agents that modulate apoptosis; e.g., one or more therapeutic agents that bind to and inhibit anti-apoptotic proteins or modulate them indirectly; e.g., one or more therapeutic agents that bind to and inhibit, or indirectly modulate, anti-apoptotic BCL-2, BCL-XL, BCL-w, MCL-1, and/or BFL-1/A1; e.g., one or more therapeutic agents that directly bind to and inhibit anti-apoptotic BCL-2 / BCL-XL; e.g., agents such as ABT-199, ABT-263 and ABT-737; e.g., ABT-737), or (where applicable) a pharmaceutically acceptable salt of the one or more therapeutic agents (as well as compositions containing the same). Also featured are methods of using such compounds, salts, combinations, and compositions, e.g., for the treatment or prevention of diseases, disorders, and conditions associated with deregulated apoptosis of cells (e.g., diseased or damaged cells; e.g., insufficient apoptosis of diseased or damaged cells or reduced apoptosis of diseased or damaged cells)..
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Humanized Monoclonal Antibodies and Methods of Use (Fri, 20 Sep 2013)
<p id="p-0001" num="0000">Disclosed is a humanized monoclonal antibody that binds to the human immunoglobulin heavy chain variable region germline gene VHI-69. The 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.</p>
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INDAZOLE COMPOUNDS AND THEIR USES (Fri, 19 Jul 2013)
<p id="p-0001" num="0000">The present application relates to therapeutic organic compounds, compositions comprising an effective amount of a therapeutic organic compound; and methods for treating and preventing disease comprising administering and effective amount of a therapeutic organic compound to a subject in need thereof.</p>
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METHODS FOR DIAGNOSING AND TREATING ONCOGENIC KRAS-ASSOCIATED CANCER (Fri, 28 Jun 2013)
Methods for diagnosing and treating cancer associated with an oncogenic Kras mutation in a subject are provided.
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STABILIZED INSULINOTROPIC PEPTIDES AND METHODS OF USE (Fri, 21 Jun 2013)
<p id="p-0001" num="0000">The present invention provides stably cross-linked insulionotropic polypeptides having superior and un-expected benefits in the treatment of conditions involving abnormal glucose homeostasis, e.g., type 2 diabetes and conditions relating to type 2 diabetes. Such benefits include, but are not limited to, extended polypeptide half-life, enhanced alpha-helicity, improved thermal stability and protease resistance, increased functional activity and pharmacologic properties, improved bioavailability when administered by any route, and improved bioavailability and gastrointestinal absorption when delivered orally, as compared to the corresponding unmodified polypeptides. The invention also provides compositions for administering the polypeptides of the invention, as well as methods for pre-paring and evaluating the polypeptides of the invention.</p>
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CD4-MIMETIC INHIBITORS OF HIV-1 ENTRY AND METHODS OF USE THEREOF (Fri, 21 Jun 2013)
Described herein are small-molecule mimics of CD4, which both enter the Phe43 cavity and target Asp368 of gpl20, the HIV-1 envelope protein. Also described herein are methods of using these compounds to inhibit the transmission or progression of HIV infection. These compounds exhibit antiviral potency greater than that of a known antiviral, NBD-556, with 100% breadth against clade B and C viruses. Importantly, the compounds do not activate HIV infection of CD4-negative, CCR5-positive cells, in contrast to NBD- 556.
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COLLATERAL GENE INACTIVATION BIOMARKERS AND TARGETS FOR CANCER THERAPY (Fri, 21 Jun 2013)
Methods for treating a subject determined to have a cancer comprising a heterozygous inactivation of a housekeeping gene (or a homozygous deletion of a functionally redundant housekeeping gene) by treating the subject with an inhibitor of the gene. For example, a subject having a cancer with an ENO gene deletion can be treated with a glycolysis inhibitor, such as an enolase inhibitor. In some aspects, a subject having a cancer with an ARS gene deletion can be treated with an ARS inhibitor.
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MEK1 Mutation Conferring Resistance to RAF and MEK Inhibitors (Fri, 07 Jun 2013)
<p id="p-0001" num="0000">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.</p>
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INHIBITORS OF C-JUN-N-TERMINAL KINASE (JNK) (Fri, 24 May 2013)
The present invention provides novel compounds according to Formula (I): where Ring A, Ring B, X, L1, L2, RA, RC, RD, RE, m, n, and p are as defined herein. Compounds of the present invention are contemplated useful for the prevention and treatment of a variety of human diseases associated with kinase activity, for example, proliferative diseases, neurodegenerative diseases, metabolic disorders, inflammatory diseases, and cardiovascular diseases.
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PYRAZOL-3-ONES THAT ACTIVATE PRO-APOPTOTIC BAX (Fri, 19 Apr 2013)
This application features pyrazol-3-one compounds that activate pro-apoptotic BAX. Also featured are methods of using such compounds, e.g., for the treatment or prevention of diseases, disorders, and conditions associated with deregulated apoptosis of cells (e.g., insufficient apoptosis of diseased or damaged cells or essentially the absence of apoptosis of diseased or damaged cells).
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ZNF365/ZFP365 BIOMARKER PREDICTIVE OF ANTI-CANCER RESPONSE (Fri, 19 Apr 2013)
The present invention is based on the identification of novel biomarkers predictive of response to anti-cancer therapies.
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SOLUBLE MTOR COMPLEXES AND MODULATORS THEREOF (Fri, 22 Mar 2013)
<p id="p-0001" num="0000">The present invention relates to small molecule modulators of mTORC1 and mTORC2, syntheses thereof, and intermediates thereto. Such small molecule modulators are useful in the treatment of proliferative diseases (e.g., benign neoplasms, cancers, inflammatory diseases, autoimmune diseases, diabetic retinopathy) and metabolic diseases. Novel small molecules are provided that inhibit one or more of mTORC1, mTORC2, and PI3K-related proteins. Novel methods of providing soluble mTORC1 and mTORC2 complexes are discussed, as well as methods of using the soluble complexes in a high-throughput manner to screen for inhibitory compounds.</p>
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MUC1 LIGAND TRAPS FOR USE IN TREATING CANCERS (Fri, 22 Feb 2013)
The present invention is directed to improved compositions for the disruption of signaling through the external domain (ED) of MUCl. Ligand traps - molecules that include MUCl ED sequences and immunoglobulin Fc domains - effectively "trap" molecules that interact with the native MUCl ED. Given the involvement of MUCl in a variety of disease states, disrupting the interaction of other molecules with MUCl ED is useful in treating these disease, in particular cancer.
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ANTI-MUC1 ANTIBODIES FOR CANCER DIAGNOSTICS (Fri, 15 Feb 2013)
The present invention is directed to antibodies binding to the MUC1 cytoplasmic domain and methods of using such antibodies to treat, diagnose, detect and monitor cancers that express the MUC1 antigen, there is provided a method of detecting MUC1 in a cell or tissue comprising (a) contacting the cell or tissue with an antibody reagent that binds immunologically to the cytoplasmic domain of MUC1; and (b) detecting the antibody reagent bound to the cell or tissue. The cell or tissue may be a cancer cell or tissue, such as a tumor biopsy, and may also be a MUC1-positive cell, tissue or biopsy.
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Bifunctional histone deacetylase inhibitors (Fri, 18 Jan 2013)
<p id="p-0001" num="0000">In recognition of the need to develop novel therapeutic agents and efficient methods for the synthesis thereof, the present invention provides novel bifunctional, trifunctional, or multifunctional compounds for inhibiting histone deacetylases, and pharmaceutically acceptable salts and derivatives thereof. The present invention further provides methods for treating disorders regulated by histone deacetylase activity (e.g., proliferative diseases, cancer, inflammatory diseases, protozoal infections, hair loss, etc.) comprising administering a therapeutically effective amount of an inventive compound to a subject in need thereof. The present invention also provides methods for preparing compounds of the invention.</p>
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BRAF mutations conferring resistance to BRAF inhibitors (Fri, 04 Jan 2013)
<p id="p-0001" num="0000">The present invention relates to methods, compositions and kits concerning resistance to treatment with an anti-cancer agent, specifically an inhibitor of BRAF. In particular embodiments, the invention concerns mutations in a BRAF sequence that confer resistance to a BRAF inhibitor. Identification of such mutations in a BRAF sequence allows the identification and design of second-generation BRAF inhibitors. Methods and kits for detecting the presence of a mutant BRAF sequence in a sample are also provided.</p>
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SIGNATURES AND DETERMINANTS ASSOCIATED WITH PROSTATE CANCER PROGRESSION AND METHODS OF USE THEREOF (Fri, 04 Jan 2013)
The present invention provides a set of DETERMINANTS (e.g., genes and gene products) that can accurately inform about the risk of cancer progression and recurrence, as well as methods of their use.
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SELECTIVE INHIBITORS OF HISTONE DEACETYLASE ISOFORM 6 AND METHODS THEREOF (Fri, 28 Dec 2012)
The described invention provides histone deacetylase (HDAC) inhibitor compounds with substituted benzimidazole, benzimidazolone and benzotriazole heterocycles showing selective inhibition of histone deacetylase isoform HDAC6. The described invention further provides methods of making such compounds and methods of inhibiting HDAC, treating HDAC- associated diseases, including cell proliferative disorders, such as cancer, autoimmune or inflammatory diseases and neurodegenerative diseases.
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BIOMARKER FOR PKC-IOTA ACTIVITY AND METHODS OF USING SAME (Fri, 21 Dec 2012)
The methods of the invention relate to the sUlpflsing detenninatlon that the level of phospohoryiation of Thr-412 of human PKC-iota or a corresponding phosphorylatable amino acid of a homolog thereof: serves as a biomarker for PKC-iota enzymatic activity (e.g., kinase activity) useful for preclinical and clinical applications. The present invention, at least in part, is based on the discovery that the level of phosphorylation ofthe threonine residue at position 412 of human PKC-iota is a reliable biomarker for PKC-iota activity suitabk for use in measuring PKC-iota enzymatic activity for preclinical and clinical applications.
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Method for preparing largazole analogs and uses thereof (Fri, 19 Oct 2012)
<p id="p-0001" num="0000">Analogs of largazole are described herein. Methods of treating cancer and blood disorders using largazole and largazole analogs and pharmaceutical compositions comprising the same are additionally described herein. Methods for preparing largazole analogs are likewise described.</p>
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TARGETING DEREGULATED WNT SIGNALING IN CANCER USING STABILIZED ALPHA-HELICES OF BCL-9 (Fri, 19 Oct 2012)
The invention provides structurally-constrained peptides by hydrocarbon stapling of a BCL9 HD2 helix for use as a therapeutic agent. The invention further provides methods and kits for use of the structurally-constrained peptide of the instant invention. The invention is based, at least in part, on the results provided herein demonstrating that hydrocarbon stapled helical peptides display excellent proteolytic, acid, and thermal stability, restore the native helical structure of the peptide, possess superior pharmacokinetic properties compared to the corresponding unmodified peptides, and are highly effective in binding to β-catenin in vitro, in cellulo, and in vivo, disrupting the BCL-9/β-catenin interaction, and thereby interfering with deregulated Wnt/β-catenin signaling for therapeutic benefit in a variety of human diseases including human cancer.
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HIGH-THROUGHPUT ASSAYS TO PROBE LEUKEMIA WITHIN THE STROMAL NICHE (Fri, 24 Aug 2012)
This invention relates to high-throughput, semi-automated methods for identifying compounds that are effective in targeting leukemia stem cells, as well as compounds identified by those methods and uses thereof for treating leukemia.
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COMPOUNDS AND METHODS FOR TARGETING LEUKEMIC STEM CELLS (Fri, 24 Aug 2012)
This invention relates to high-throughput, semi-automated methods for identifying compounds that are effective in targeting leukemia stem cells, as well as compounds identified by those methods and uses thereof for treating leukemia.
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HISTONE DEACETYLASE INHIBITORS AND METHODS OF USE THEREOF (Fri, 24 Aug 2012)
The present invention provides novel compounds for inhibiting histone deacetylases, and pharmaceutically acceptable salts and derivatives thereof. The present invention further provides methods for treating disorders regulated by histone deacetylase activity (e.g., proliferative diseases, cancer, inflammatory diseases, protozoal infections, hair loss, etc.) comprising administering a therapeutically effective amount of a compound of the invention to a subject in need thereof. The present invention also provides methods for preparing compounds of the invention.
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Class- and isoform-specific HDAC inhibitors and uses thereof (Fri, 17 Aug 2012)
<p id="p-0001" num="0000">The present invention relates to compounds of the following formula</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="48.94mm" wi="53.85mm" file="US08716344-20140506-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <br/> wherein R<sub>3 </sub>is a fluorescent tag. Another aspect of the invention provides an assay for determining the inhibitory effect of a test compound on an HDAC protein comprising: incubating the HDAC protein with a substrate of the above formula in the presence of a test compound; and determining the activity of the HDAC protein. </p>
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METHOD OF INHIBITING HAMARTOMA TUMOR CELLS (Fri, 17 Aug 2012)
Dimorpholinopyrimidines are useful for inhibiting growth or proliferation of hamartoma tumor cells. Because the Dimorpholinopyrimidines inhibit the growth and proliferation of hamartoma tumor cells they are also useful in treating PTEN hamartoma tumor syndromes. The therapeutic and prophylactic treatments provided by this invention are practiced by administering to a patient in need thereof an amount of a compound of dimorpholinopyrimidine derivative that is effective to inhibit growth or proliferation of the hamartoma tumor cells.
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SIGNATURES AND DETERMINANTS ASSOCIATED WITH CANCER AND METHODS OF USE THEREOF (Fri, 08 Jun 2012)
The present invention provides methods of detecting cancer using biomarkers.
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Fused 2-aminothiazole compounds (Fri, 13 Apr 2012)
<p id="p-0001" num="0000">The present application relates to therapeutic organic compounds of formula (I),</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="24.72mm" wi="64.43mm" file="US08765747-20140701-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <br/> wherein Q, R1, R2, R3, and R4 are defined herein. The invention also relates to pharmaceutical compositions comprising an effective amount of a therapeutic organic compound; and methods for treating and preventing disease such as cancer comprising administering and effective amount of a therapeutic organic compound to a subject in need thereof. </p>
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Antagonists of MUC1 (Fri, 24 Feb 2012)
<p id="p-0001" num="0000">The present invention is directed to improved compositions for cellular delivery of peptides. Using segments of only 3-5 positively-charged residues, one can effectively transfer peptides, including therapeutic peptides, into cells. Also provided are modified peptides such as those include stapled and cyclized peptide technology, as well as peptoids/peptidomimetics.</p>
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Conformationally stabilized HIV envelope immunogens (Fri, 10 Feb 2012)
<p id="p-0001" num="0000">Stabilized forms of gp120 polypeptide, nucleic acids encoding these stabilized forms, vectors comprising these nucleic acids, and methods of using these polypeptides, nucleic acids, vectors and host cells are disclosed. Crystal structures and computer systems including atomic coordinates for stabilized forms of gp120, and gp120 with an extended V3 loop, and methods of using these structures and computer systems are also disclosed.</p>
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STABILIZED INSULINOTROPIC PEPTIDES AND METHODS OF USE (Fri, 13 Jan 2012)
The present invention provides stably crosslinked insulionotropic polypeptides having superior and unexpected benefits in the treatment of conditions involving abnormal glucose homeostasis, e.g., type 2 diabetes and conditions relating to type 2 diabetes. Such benefits include, but are not limited to, extended polypeptide half-life, enhanced alpha-helicity, improved thermal stability and protease resistance, increased functional activity and pharmacologic properties, improved bioavailability when administered by any route, and improved bioavailability and gastrointestinal absorption when delivered orally, as compared to the corresponding unmodified polypeptides. The invention also provides compositions for administering the polypeptides of the invention, as well as methods for preparing and evaluating the polypeptides of the invention.
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COMPOSITIONS AND METHODS FOR THE TREATMENT OF VIRAL INFECTIONS (Fri, 30 Dec 2011)
<p id="p-0001" num="0000">The invention provides compositions, kits and methods utilizing polypeptides having a viral alpha-helix heptad repeat domain in a stabilized a-helical structure (herein also referred to as SAH). The compositions are useful for treating and/or preventing viral infections. The invention is based, at least in part, on the result provided herein demonstrating that viral hydrocarbon stapled alpha helical peptides display excellent proteolytic, acid, and thermal stability, restore the native alpha-helical structure of the peptide, are highly effective in interfering with the viral fusogenic process, and possess superior pharmacokinetic properties compared to the corresponding unmodified peptides.</p>
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SMALL MOLECULE MYRISTATE INHIBITORS OF BCR-ABL AND METHODS OF USE (Fri, 23 Dec 2011)
<p id="p-0001" num="0000">The present invention provides novel heteroaryl compounds that are linked to an aryl group via an amine linker. Such compounds are useful for the treatment of cancers.</p>
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Phosphorylated RaIA (Fri, 16 Dec 2011)
<p id="p-0001" num="0000">Antibodies that are specific for human Ra1A that is phosphorylated at one or both of Ser183 and Ser194 are described as various methods such antibodies, including diagnostic methods and screening methods.</p>
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A MEK 1 MUTATION CONFERRING RESISTANCE TO RAF AND MEK INHIBITORS (Fri, 16 Dec 2011)
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 MEKl sequence are also provided.
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A MEK1 MUTATION CONFERRING RESISTANCE TO RAF AND MEK INHIBITORS (Fri, 16 Dec 2011)
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 MEKl sequence are also provided.</p>
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HUMANIZED MONOCLONAL ANTIBODIES AND METHODS OF USE (Fri, 09 Dec 2011)
Disclosed is a humanized monoclonal antibody that binds to the human immunoglobulin heavy chain variable region gerrnline gene VHI -69. The 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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HUMANIZED MONOCLONAL ANTIBODIES AND METHODS OF USE (Fri, 09 Dec 2011)
Disclosed is a humanized monoclonal antibody that binds to the human immunoglobulin heavy chain variable region gerrnline gene VHI -69. The 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.</p>
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Soluble mTOR complexes and modulators thereof (Fri, 25 Nov 2011)
<p id="p-0001" num="0000">The present invention relates to small molecule modulators of mTORC1 and mTORC2, syntheses thereof, and intermediates thereto. Such small molecule modulators are useful in the treatment of proliferative diseases (e.g., benign neoplasms, cancers, inflammatory diseases, autoimmune diseases, diabetic retinopathy) and metabolic diseases. Novel small molecules are provided that inhibit one or more of mTORC1, mTORC2, and PI3K-related proteins. Novel methods of providing soluble mTORC1 and mTORC2 complexes are discussed, as well as methods of using the soluble complexes in a high-throughput manner to screen for inhibitory compounds.</p>
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COMPOSITIONS AND METHODS FOR MODULATING METABOLISM (Fri, 18 Nov 2011)
The invention provides compositions comprising an effective amount of an agent that inhibits a BET protein (e.g., Brd2, Brd3, Brd4), and methods of using such compositions for treating or preventing metabolic syndrome, obesity, type II diabetes, insulin resistance, and related disorders characterized by undesirable alterations in metabolism or fat accumulation.
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COMPOSITIONS AND METHODS FOR TREATING NEOPLASIA, INFLAMMATORY DISEASE AND OTHER DISORDERS (Fri, 18 Nov 2011)
The invention features compositions and methods for treating or preventing a neoplasia. More specifically, the invention provides compositions and methods for disrupting the interaction of a BET family polypeptide comprising a bromodomain with chromatin (e.g., disrupting a bromodomain interaction with an acetyl-lysine modification present on a histone N-terminal tail).
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MALE CONTRACEPTIVE COMPOSITIONS AND METHODS OF USE (Fri, 18 Nov 2011)
The invention relates to compositions and methods for effecting male contraception.
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COMPOSITIONS AND METHODS FOR TREATING LEUKEMIA (Fri, 18 Nov 2011)
Treatment of acute myeloid leukemia with an agent that inhibits BRD4 is disclosed.
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MALE CONTRACEPTIVE COMPOSITIONS AND METHODS OF USE (Fri, 18 Nov 2011)
The invention relates to compositions and methods for effecting male contraception.</p>
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COMPOSITIONS AND METHODS FOR MODULATING METABOLISM (Fri, 18 Nov 2011)
The invention provides compositions comprising an effective amount of an agent that inhibits a BET protein (e.g., Brd2, Brd3, Brd4), and methods of using such compositions for treating or preventing metabolic syndrome, obesity, type II diabetes, insulin resistance, and related disorders characterized by undesirable alterations in metabolism or fat accumulation.</p>
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COMPOSITIONS AND METHODS FOR TREATING LEUKEMIA (Fri, 18 Nov 2011)
The invention provides compositions, methods, and kits for the treatment of acute myeloid leukemia in a subject.</p>
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COMPOSITIONS AND METHODS FOR TREATING NEOPLASIA, INFLAMMATORY DISEASE AND OTHER DISORDERS (Fri, 18 Nov 2011)
The invention features compositions and methods for treating or preventing a neoplasia. More specifically, the invention provides compositions and methods for disrupting the interaction of a BET family polypeptide comprising a bromodomain with chromatin (e.g., disrupting a bromodomain interaction with an acetyl-lysine modification present on a histone N-terminal tail).</p>
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NUCLEIC ACID NANOTUBE LIQUID CRYSTALS AND USE FOR NMR STRUCTURE DETERMINATION OF MEMBRANE PROTEINS (Fri, 28 Oct 2011)
<p id="p-0001" num="0000">Compositions and methods for preparing nucleic acid nanotubes using DNA origami techniques are described, which provide for nanotubes of predictable and uniform length. The nucleic acid nanotubes thus formed are suitable as liquid crystal preparations enabling liquid-crystal NMR spectroscopy of proteins solubilized in detergent.</p>
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CELASTROL, GEDUNIN, AND DERIVATIVES THEREOF AS HSP90 INHIBITORS (Fri, 28 Oct 2011)
<p id="p-0001" num="0000">Based on the discovery that celastrol and gedunin are Hsp90 inhibitors, the present invention provides novel inhibitors of Hsp90. and pharmaceutically acceptable salts, derivatives, and compositions thereof. The invention provides two classes of compounds. One class includes celastrol and its derivatives. The other class includes gedunin and its derivatives. The present invention further provides methods for treating disorders wherein Hsρ90 inhibition is desired (e.g., proliferative diseases, cancer, inflammatory diseases, fungal infections, etc.) comprising administering a therapeutically effective amount of an inventive compound to a subject in need thereof. Celastrol, gedunin, and derivatives thereof are particularly useful in the treatment of prostate cancer, breast cancer, ovarian cancer, lung cancer, and leukemia.</p>
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Signatures and PCDeterminants Associated with Prostate Cancer and Methods of Use Thereof (Fri, 28 Oct 2011)
<p id="p-0001" num="0000">The present invention provides methods of detecting cancer using biomarkers.</p>
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SMALL MOLECULE INHIBITORS OF MUC1 AND METHODS OF IDENTIFYING THE SAME (Fri, 23 Sep 2011)
The invention provides methods for the identification of small molecules that inhibit MUC1 oligomerization, and the functions flowing therefrom. In addition, small molecules that prevent MUC1 oligomerization, such as some flavonoids, are disclosed. Identified molecules will find use in treating a variety of MUC1 -related inflammatory conditions, including MUC1 -related cancers. The screening methods involve two MUC1 -derived peptides comprising at least four consecutive residues of the MUC1 sequence and the motive CQC, e.g. CQCR, CQCRR, CQCRRR, CQCRRRR, CQCRRK and CQCRRKN.
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INDAZOLE COMPOUNDS AS KINASE ACTIVITY MODULATORS FOR THE TREATMENT OF CANCER AND RELATED DISORDERS (Fri, 23 Sep 2011)
The present application relates to substituted 1 H-indazole compounds that are useful as kinase-activity modulators in the treatment of cancer and related diseases.
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INDAZOLE COMPOUNDS AND THEIR USES (Fri, 23 Sep 2011)
The present application relates to therapeutic organic compounds, compositions comprising an effective amount of a therapeutic organic compound; and methods for treating and preventing disease comprising administering and effective amount of a therapeutic organic compound to a subject in need thereof.</p>
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CHEMICAL MODULATORS OF PRO-APOPTOTIC BAX AND BCL-2 POLYPEPTIDES (Fri, 09 Sep 2011)
<p id="p-0001" num="0000">The invention provides a method for identifying a compound which modulates the activity of a BCL-2 family polypeptide, the method comprising: a) contacting said BCL-2 family polypeptide with a compound under conditions suitable for modulation of the activity of said BCL-2 family polypeptide; and b) detecting modulation of the activity of said BCL-2 family polypeptide by the compound, wherein the compound interacts with a binding site comprising one or more of an α1 helix, α2 helix, a loop between α1-α2, α.6 helix, and select residues of α4, α.5, and α.8 helices in said BCL-2 family polypeptide; wherein the interaction of the compound with the binding site occurs at a horizontal hydrophobic groove with or without a perimeter of charged and hydrophilic residues, a superior juxta-loop, an inferior juxta-loop, or combination thereof.</p>
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BRAF MUTATIONS CONFERRING RESISTANCE TO BRAF INHIBITORS (Fri, 02 Sep 2011)
The present invention relates to methods, compositions and kits concerning resistance to treatment with an anti-cancer agent, specifically an inhibitor of BRAF. In particular embodiments, the invention concerns mutations in a BRAF sequence that confer resistance to a BRAF inhibitor. Identification of such mutations in a BRAF sequence allows the identification and design of second-generation BRAF inhibitors. Methods and kits for detecting the presence of a mutant BRAF sequence in a sample are also provided.
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BRAF MUTATIONS CONFERRING RESISTANCE TO BRAF INHIBITORS (Fri, 02 Sep 2011)
The present invention relates to methods, compositions and kits concerning resistance to treatment with an anti-cancer agent, specifically an inhibitor of BRAF. In particular embodiments, the invention concerns mutations in a BRAF sequence that confer resistance to a BRAF inhibitor. Identification of such mutations in a BRAF sequence allows the identification and design of second-generation BRAF inhibitors. Methods and kits for detecting the presence of a mutant BRAF sequence in a sample are also provided.</p>
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Molecular Determinants Associated With Prostate Cancer And Methods Of Use Thereof (Fri, 26 Aug 2011)
<p id="p-0001" num="0000">The present invention provides methods of treating cancer by inhibiting pserine threonine kinase activity and detecting cancer using biomarkers.</p>
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MUC1, CASPASE-8, and DED-CONTAINING PROTEINS (Fri, 26 Aug 2011)
<p id="p-0001" num="0000">The disclosure features a variety of compositions and methods for modulating an interaction between MUC1 and caspase-8 and/or an interaction between MUC1 and a DED-containing protein (e.g., an anti-apoptotic DED-containing protein or a pro-apoptotic DED-containing protein). Such methods and compositions are useful for the treatment or prevention of, e.g., a variety of pathological disorders characterized by elevated or decreased levels of apoptosis. Moreover, the compositions and methods are also useful to identify, design, and generate compounds that modulate the interactions. The compounds and/or pharmaceutical compositions containing the compounds can be used in the treatment of disease.</p>
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IMPROVED ANTAGONISTS OF MUC1 (Fri, 19 Aug 2011)
The present invention is directed to improved compositions for cellular delivery of peptides. Using segments of only 3-5 positively-charged residues, one can effectively transfer peptides, including therapeutic peptides, into cells. Also provided are modified peptides such as those include stapled and cyclized peptide technology, as well as peptoids/peptidomimetics.
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MUC-1 CYTOPLASMIC DOMAIN PEPTIDES AS INHIBITORS OF CANCER (Thu, 11 Aug 2011)
The invention provides for peptides from the MUCl cytoplasmic domain and methods of use therefor. These peptides can inhibit MUCl oligomerization, thereby preventing tumor cell growth, inducing tumor cell apoptosis and necrosis of tumor tissue in vivo.
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SMALL MOLECULES FOR THE MODULATION OF MCL-1 AND METHODS OF MODULATIING CELL DEATH, CELL DIVISION, CELL DIFFERENTIATION AND METHODS OF TREATING DISORDERS (Fri, 05 Aug 2011)
This invention relates to compounds which selectively bind to the survival protein MCL-1 with high affinity and selectivity, pharmaceutical compositions containing such compounds and the use of those compounds or compositions for modulating MCL-1 activity and for treating hyperproliferative disorders, angiogenesis disorders, cell cycle regulation disorders, autophagy regulation disorders, inflammatory disorders, and/or infectious disorders and/or for enhancing cellular engraftment and/or wound repair, as a sole agent or in combination with other active ingredients.
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SMALL MOLECULES FOR THE MODULATION OF MCL-1 AND METHODS OF MODULATING CELL DEATH, CELL DIVISION, CELL DIFFERENTIATION AND METHODS OF TREATING DISORDERS (Fri, 05 Aug 2011)
This invention relates to compounds which selectively bind to the survival protein MCL-1 with high affinity and selectivity, pharmaceutical compositions containing such compounds and the use of those compounds or compositions for modulating MCL-1 activity and for treating hyperproliferative disorders, angiogenesis disorders, cell cycle regulation disorders, autophagy regulation disorders, inflammatory disorders, and/or infectious disorders and/or for enhancing cellular engraftment and/or wound repair, as a sole agent or in combination with other active ingredients.</p>
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SOLUBLE MTOR COMPLEXES AND MODULATORS THEREOF (Thu, 04 Aug 2011)
The present invention relates to small molecule modulators of mTORC1 and mTORC2, syntheses thereof, and intermediates thereto. Such small molecule modulators are useful in the treatment of proliferative diseases (e.g., benign neoplasms, cancers, inflammatory diseases, autoimmune diseases, diabetic retinopathy) and metabolic diseases. Novel small molecules are provided that inhibit one or more of mTORC1, mTORC2, and PI3K-related proteins. Novel methods of providing soluble mTORC1 and mTORC2 complexes are discussed, as well as methods of using the soluble complexes in a high-throughput manner to screen for inhibitory compounds.
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SIGNATURE AND DETERMINANTS ASSOCIATED WITH METASTASIS AND METHODS OF USE THEREOF (Fri, 29 Jul 2011)
<p id="p-0001" num="0000">The present invention provides methods of detecting cancer using biomarkers.</p>
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COMPOSITIONS, KITS, AND METHODS FOR IDENTIFICATION, ASSESSMENT, PREVENTION, AND THERAPY OF METABOLIC DISORDERS (Fri, 29 Jul 2011)
The invention provides methods and compositions for selectively promoting anti- metabolic disorder activity over classical PPAR gamma activation through modulation of PPAR gamma phosphorylation (e.g., Ser-273 phosphorylation of murine peroxisome proliferator activated receptor gamma (PPAR gamma) 2 or a corresponding serine residue in a murine PPAR gamma 2 homolog, including a human). Also provided are methods for preventing, treating, or predictiving responsiveness of therapies for metabolic disorders in a subject through selective inhibition of such PPAR gamma phosphorylation. Further provided are methods for identifying compounds that are capable of modulating such PPAR gamma phosphorylation.
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TYPE II RAF KINASE INHIBITORS (Fri, 29 Jul 2011)
The present invention relates to novel compounds which are able to modulate b-raf kinases, and the use of such compounds in the treatment of various diseases, disorders or conditions.
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TYPE II RAF KINASE INHIBITORS (Fri, 29 Jul 2011)
The present invention relates to novel compounds which are able to modulate b-raf kinases, and the use of such compounds in the treatment of various diseases, disorders or conditions.</p>
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COMPOSITIONS, KITS, AND METHODS FOR IDENTIFICATION, ASSESSMENT, PREVENTION, AND THERAPY OF METABOLIC DISORDERS (Fri, 29 Jul 2011)
The invention provides methods and compositions for selectively promoting anti- metabolic disorder activity over classical PPAR gamma activation through modulation of PPAR gamma phosphorylation (e.g., Ser-273 phosphorylation of murine peroxisome proliferator activated receptor gamma (PPAR gamma) 2 or a corresponding serine residue in a murine PPAR gamma 2 homolog, including a human). Also provided are methods for preventing, treating, or predictiving responsiveness of therapies for metabolic disorders in a subject through selective inhibition of such PPAR gamma phosphorylation. Further provided are methods for identifying compounds that are capable of modulating such PPAR gamma phosphorylation. </p>
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Deacetylase inhibitors and uses thereof (Fri, 15 Jul 2011)
<p id="p-0001" num="0000">The present invention provides novel compounds of formula (I) and pharmaceutical compositions thereof. The inventive compounds are useful as deacetylase inhibitors (e.g., histone deacetylase inhibitors) and may be useful in the treatment of proliferative diseases such as cancer. In particular, the inventive compounds are HDAC6 inhibitors. The invention also provide synthetic methods for preparing the inventive compounds.</p>
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COMPOSITIONS AND METHODS FOR INHIBITION OF RETROVIRUSES (Fri, 17 Jun 2011)
<p id="p-0001" num="0000">Described herein are methods and compositions for the inhibition of retroviral integration and replication. The methods and compositions inhibit the activity of one or more components of the SET complex or base excision repair enzymes and induce autointegration of retroviral double-stranded nucleic acid.</p>
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COMPOUNDS AND COMPOSITIONS USEFUL FOR THE TREATMENT OF MALARIA (Fri, 17 Jun 2011)
<p id="p-0001" num="0000">The invention provides a class of compounds of formula I, pharmaceutical compositions comprising such compounds and methods of using such compounds to treat or prevent malaria.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="30.65mm" wi="60.20mm" file="US20110144107A1-20110616-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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CLASS- AND ISOFORM-SPECIFIC HDAC INHIBITORS AND USES THEREOF (Fri, 18 Feb 2011)
HDAC inhibitors of the general formula (I) and (II) and pharmaceutically acceptable salts thereof, as described herein, are useful as inhibitors of histone deacetylases or other deacetylases, and thus are useful for the treatment of various diseases and disorders associated with acetylase/deacetylase activity as described herein (e.g., cancer). In certain embodiments, the compounds of the invention selectively target either a class or isoform of the HDAC family. Another aspect of the invention provides an assay for determining the inhibitory effect of a test compound on an HDAC protein comprising: incubating the HDAC protein with a substrate of general formula (IIIc) in the presence of a test compound; and determining the activity of the HDAC protein.
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REAGENTS FOR INDUCING AN IMMUNE RESPONSE (Fri, 11 Feb 2011)
<p id="p-0001" num="0000">The present disclosure relates to reagents (antigenic and/or immunogenic reagents) and kits that are useful in a variety of in vitro, in vivo, and ex vivo methods including, e.g., methods for inducing an immune response, or for generating an antibody, in a subject. The reagents described herein can be used in the treatment or prevention of HIV-1 infections. In addition, the disclosure provides methods and compositions useful for designing (or identifying) an agent that binds to an membrane proximal external region (MPER) of an HIV-1 gp160 polypeptide or an agent that inhibits the fusion of an HIV-1 particle to a cell.</p>
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Inhibition of inflammation using antagonists of MUC1 (Fri, 21 Jan 2011)
<p id="p-0001" num="0000">The invention provides for peptides from the MUC1 cytoplasmic domain and methods of use therefor. These peptides can inhibit MUC1 oligomerization, inhibit the interaction of MUC1 with NF-κB or a STAT, and block inflammatory response mediated by NF-κB or STAT signaling.</p>
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STRUCTURED VIRAL PEPTIDE COMPOSITIONS AND METHODS OF USE (Fri, 24 Dec 2010)
The invention provides structurally constrained viral peptides for use as therapeutic and vaccination agents, and for the production of antibodies for use in a number of applications including as therapeutic agents. The invention further provides methods and kits for use of the structurally constrained peptides and antibodies of the instant invention. The invention is based, at least in part, on the result provided herein demonstrating that viral hydrocarbon stapled helical peptides display excellent proteolytic, acid, and thermal stability, restore the native helical structure of the peptide, are highly effective in interfering with the viral fusogenic process, and possess superior pharmacokinetic properties compared to the corresponding unmodified peptides.
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STRUCTURED VIRAL PEPTIDE COMPOSITIONS AND METHODS OF USE (Fri, 24 Dec 2010)
The invention provides structurally constrained viral peptides for use as therapeutic and vaccination agents, and for the production of antibodies for use in a number of applications including as therapeutic agents. The invention further provides methods and kits for use of the structurally constrained peptides and antibodies of the instant invention. The invention is based, at least in part, on the result provided herein demonstrating that viral hydrocarbon stapled helical peptides display excellent proteolytic, acid, and thermal stability, restore the native helical structure of the peptide, are highly effective in interfering with the viral fusogenic process, and possess superior pharmacokinetic properties compared to the corresponding unmodified peptides. </p>
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INHIBITION 0F INFLAMMATION USING ANTAGONISTS OF MUC1 (Fri, 03 Dec 2010)
The invention provides for peptides from the MUCl cytoplasmic domain and methods of use therefor. These peptides can inhibit MUCl oligomerization, inhibit the interaction of MUCl with NF -KB or a STAT, and block inflammatory response mediated by NF-κB or STAT signaling.
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INHIBITION 0F INFLAMMATION USING ANTAGONISTS OF MUC1 (Fri, 03 Dec 2010)
The invention provides for peptides from the MUC1 cytoplasmic domain and methods of use therefor. These peptides can inhibit MUC1 oligomerization, inhibit the interaction of MUC1 with NF -KB or a STAT, and block inflammatory response mediated by NF-.kappa.B or STAT signaling. </p>
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METHODS AND COMPOSITIONS FOR MODULATING BCL-2 FAMILY POLYPEPTIDES (Fri, 12 Nov 2010)
<p id="p-0001-en" num="0000">The present invention is based, at least in part, on the identification of a novel active site on BCL-2 family polypeptide such as BAX, which when bound by a compound, modifies the activity of the BCL-2 family polypeptide.</p>
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EGFR INHIBITORS AND METHODS OF TREATING DISORDERS (Fri, 12 Nov 2010)
The present invention relates to novel pyrimidine, pyrrolo-pyrimidine, pyrrolo-pyridine, pyridine, purine and triazine compounds which are able to modulate epidermal growth factor receptor (EGFR), including Her-kinases, and the use of such compounds in the treatment of various diseases, disorders or conditions.
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EGFR INHIBITORS AND METHODS OF TREATING DISORDERS (Fri, 12 Nov 2010)
The present invention relates to novel pyrimidine, pyrrolo-pyrimidine, pyrrolo-pyridine, pyridine, purine and triazine compounds which are able to modulate epidermal growth factor receptor (EGFR), including Herkinases, and the use of such compounds in the treatment of various diseases, disorders or conditions. </p>
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Enrichment of a target sequence (Fri, 13 Aug 2010)
<p id="p-0001" num="0000">The present invention is directed to methods, compositions, software and devices for enriching low abundance alleles from a sample. The method is based in part on a modified nucleic acid amplification protocol that includes incubating the reaction mixture at a critical denaturing temperature or “Tc”. By employing the present invention the current detection limits of all PCR-based technologies are greatly improved.</p>
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Novel Compounds for Enhancing MHC Class II Therapies (Fri, 23 Jul 2010)
<p id="p-0001-en" num="0000">The invention provides classes of novel compounds that accelerate peptide loading to DR in the absence of DM and related pharmaceutical compositions. The invention also provides conjugates of these compounds with peptides, antigens or other MHC-based therapeutics, including peptides that self-catalyze their loading onto MHC Class II molecules. Methods are provided for modulating an immune response in a subject. Also disclosed are methods of using the novel compounds, e.g., in combination with MHC-based therapeutics, for the treatment of autoimmune diseases and for the manufacture of medicaments. Methods of improving loading of viral peptides and tumor peptides for enhancing the CD4 T cell response following vaccination against viruses or tumors, and related vaccines, are also provided.</p>
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PYRIMIDO-DIAZEPINONE KINASE SCAFFOLD COMPOUNDS AND METHODS OF TREATING DISORDERS (Fri, 16 Jul 2010)
The present invention relates to novel pyrimido-diazepinone compounds, methods of modulating protein kinases, including MPSl (TTK), ERK5 (BMKl, MAPK7), polo kinase 1,2,3, or 4, Ackl, Ack2, AbI, DCAMKLl, ABLl, AbI mutants, DCAMKL2, ARK5, BRK, MKNK2, FGFR4, TNKl, PLKl, ULK2, PLK4, PRKDl, PRKD2, PRKD3, ROS l, RPS6KA6, TAOKl, TAOK3, TNK2, Bcr-Abl, GAK, cSrc, TPR-Met, Tie2, MET, FGFR3, Aurora, AxI, Bmx, BTK, c-kit, CHK2, Flt3, MST2, p70S6K, PDGFR, PKB, PKC, Raf, ROCK-H, Rskl, SGK, TrkA, TrkB and TrkC, and the use of such compounds in the treatment of various diseases, disorders or conditions.
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METHODS AND COMPOSITIONS FOR SPECIFIC MODULATION OF MCL-1 (Fri, 18 Jun 2010)
A series of stapled BCL-2 family peptide helices were identified as able to target the survival protein MCL-I with high affinity and a subset with unprecedented selectivity. Agents and methods for selective pharmacologic neutralization of MCL-I are provided for drug discovery and therapeutic uses, including use in overcoming the apoptotic resistance of cancer and other diseases associated with impaired cell death.
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MEK MUTATIONS CONFERRING RESISTANCE TO MEK INHIBITORS (Fri, 18 Jun 2010)
The present invention relates to methods, compositions and kits concerning resistance to treatment with an anti-cancer agent, specifically an inhibitor of MEK. In particular embodiments, the invention concerns mutations in a MEK sequence that confer resistance to a MEK inhibitor. Identification of such mutations in a MEK sequence allows the identification and design of second-generation MEK inhibitors. Methods and kits for detecting the presence of a mutant MEK sequence in a sample are also provided.
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METHODS AND COMPOSITIONS FOR SPECIFIC MODULATION OF MCL-1 (Fri, 18 Jun 2010)
A series of stapled BCL-2 family peptide helices were identified as able to target the survival protein MCL-I with high affinity and a subset with unprecedented selectivity. Agents and methods for selective pharmacologic neutralization of MCL-I are provided for drug discovery and therapeutic uses, including use in overcoming the apoptotic resistance of cancer and other diseases associated with impaired cell death. </p>
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MUC-1 cytoplasmic domain peptides as inhibitors of cancer (Fri, 21 May 2010)
<p id="p-0001" num="0000">The invention provides for peptides from the Mucin 1 (MUC1) cytoplasmic domain and methods of use therefor. These peptides can inhibit MUC1 oligomerization, thereby preventing tumor cell growth, inducing tumor cell apoptosis and necrosis of tumor tissue in vivo.</p>
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SMALL MOLECULE CD4 MIMETICS AND USES THEREOF (Sat, 15 May 2010)
The invention provides for compounds of formula I: wherein Z is absent or (CRARB)nW; each RA and RB is independently (i) H, alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, aralkyl, heteroaralkyl, haloalkyl, each of which may be optionally substituted; (ii) OH, ORc, NH2, NHRc, NRcRc, SH, S(O)mRc; or (iii) RA and RB together form C(O); W is absent, C(O), C(O)O, C(O)NRcRc, O, S(O)m, or NRcRc; Y is an optionally substituted heterocyclic, optionally substituted heteroaryl, optionally substituted cycloalkyl, optionally substituted aryl, or NRXRY; wherein Rx and Ry are each independenly H, alkyl or aryl; X1 is selected from the group consisting of halogen, methyl, and hydroxyl; X2 is a halogen; each Rc is independently alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, aralkyl, or heteroaralkyl, each of which may be optionally substituted; m is O, 1, or 2; and n is 1, 2, 3, 4, 5, or 6; and pharmaceutically acceptable salts thereof.
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MUC1 and galectin-3 (Fri, 23 Apr 2010)
<p id="p-0001" num="0000">The invention provides methods of identifying and making compounds that inhibit the interaction between MUC1 and galectin-3. Also embraced by the invention are in vivo and in vitro methods of inhibiting such an interaction and of inhibiting the expression of galectin-3 by a cell.</p>
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MUC-1 CYTOPLASMIC DOMAIN PEPTIDES AS INHIBITORS OF CANCER (Fri, 23 Apr 2010)
The invention provides for peptides from the MUCl cytoplasmic domain and methods of use therefor. These peptides can inhibit MUCl oligomerization, thereby preventing tumor cell growth, inducing tumor cell apoptosis and necrosis of tumor tissue in vivo.
>> read more

SOLUBLE MTOR COMPLEXES AND MODULATORS THEREOF (Fri, 23 Apr 2010)
The present invention relates to small molecule modulators of mTORC1 and mTORC2, syntheses thereof, and intermediates thereto. Such small molecule modulators are useful in the treatment of proliferative diseases (e.g., benign neoplasms, cancers, inflammatory diseases, autoimmune diseases, diabetic retinopathy) and metabolic diseases. Novel small molecules are provided that inhibit one or more of mTORC1, mTORC2, and PI3K-related proteins. Novel methods of providing soluble mTORC1 and mTORC2 complexes are discussed, as well as methods of using the soluble complexes in a high-throughput manner to screen for inhibitory compounds.
>> read more

MUC-1 CYTOPLASMIC DOMAIN PEPTIDES AS INHIBITORS OF CANCER (Fri, 23 Apr 2010)
The invention provides for peptides from the MUC1 cytoplasmic domain and methods of use therefor. These peptides can inhibit MUC1 oligomerization, thereby preventing tumor cell growth, inducing tumor cell apoptosis and necrosis of tumor tissue in vivo. </p>
>> read more

CHEMICAL MODULATORS OF PRO-APOPTOTIC BAX AND BCL-2 POLYPEPTIDES (Fri, 16 Apr 2010)
The invention provides a method for identifying a compound which modulates the activity of a BCL-2 family polypeptide, the method comprising: a) contacting said BCL-2 family polypeptide with a compound under conditions suitable for modulation of the activity of said BCL-2 family polypeptide; and b) detecting modulation of the activity of said BCL-2 family polypeptide by the compound, wherein the compound interacts with a binding site comprising one or more of an αl helix, α2 helix, a loop between αl-α2, α.6 helix, and select residues of α4, α.5, and α.8 helices in said BCL-2 family polypeptide; wherein the interaction of the compound with the binding site occurs at a horizontal hydrophobic groove with or without a perimeter of charged and hydrophilic residues, a superior juxta-loop, an inferior juxta-loop, or combination thereof.
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CHEMICAL MODULATORS OF PRO-APOPTOTIC BAX AND BCL-2 POLYPEPTIDES (Fri, 16 Apr 2010)
The invention provides a method for identifying a compound which modulates the activity of a BCL-2 family polypeptide, the method comprising: a) contacting said BCL-2 family polypeptide with a compound under conditions suitable for modulation of the activity of said BCL-2 family polypeptide; and b) detecting modulation of the activity of said BCL-2 family polypeptide by the compound, wherein the compound interacts with a binding site comprising one or more of an .alpha.1 helix, .alpha.2 helix, a loop between .alpha.1-.alpha.2, .alpha., .6 helix, and select residues of .alpha.4, .alpha..5, and .alpha..8 helices in said BCL-2 family polypeptide; wherein the interaction of the compound with the binding site occurs at a horizontal hydrophobic groove with or without a perimeter of charged and hydrophilic residues, a superior juxta-loop, an inferior juxta- loop, or combination thereof. </p>
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COMPOSITIONS, KITS AND METHODS FOR THE DIAGNOSIS, PROGNOSIS, AND MONITORING OF CANCER USING GOLPH3 (Fri, 09 Apr 2010)
The present invention is based, in part, on the discovery that GOLPH3 plays a role in cancer, including lung, ovarian, pancreatic, liver, breast, prostate, and colon carcinomas, as well as melanoma and multiple myeloma. Accordingly, the invention relates to compositions, kits, and methods for diagnosing, prognosing, and monitoring cancer, e.g., lung, ovarian, pancreatic, liver, breast, prostate, and colon carcinomas, as well as melanoma and multiple myeloma.
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COMPOSITIONS, KITS AND METHODS FOR THE DIAGNOSIS, PROGNOSIS, AND MONITORING OF CANCER USING GOLPH3 (Fri, 09 Apr 2010)
The present invention is based, in part, on the discovery that GOLPH3 plays a role in cancer, including lung, ovarian, pancreatic, liver, breast, prostate, and colon carcinomas, as well as melanoma and multiple myeloma. Accordingly, the invention relates to compositions, kits, and methods for diagnosing, prognosing, and monitoring cancer, e.g., lung, ovarian, pancreatic, liver, breast, prostate, and colon carcinomas, as well as melanoma and multiple myeloma. </p>
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Histone deacetylase inhibitors (Fri, 05 Mar 2010)
<p id="p-0001" num="0000">In recognition of the need to develop novel therapeutic agents, the present invention provides novel histone deacetylase inhibitors. These compounds include an ester bond making them sensitive to deactivation by esterases. Therefore, these compounds are particularly useful in the treatment of skin disorders. When the compounds reaches the bloodstream, an esterase or an enzyme with esterase activity cleaves the compound into biologically inactive fragments or fragments with greatly reduced activity Ideally these degradation products exhibit a short serum and/or systemic half-life and are eliminated rapidly. These compounds and pharmaceutical compositions thereof are particularly useful in treating cutaneous T-cell lymphoma, neurofibromatosis, psoriasis, hair loss, skin pigmentation, and dermatitis, for example. The present invention also provides methods for preparing compounds of the invention and intermediates thereto.</p>
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Method for preparing largazole analogs and uses thereof (Fri, 05 Feb 2010)
<p id="p-0001" num="0000">Analogs of largazole are described herein. Methods of treating cancer and blood disorders using largazole and largazole analogs and pharmaceutical compositions comprising the same are additionally described herein. Methods for preparing largazole analogs are likewise described.</p>
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DEACETYLASE INHIBITORS AND USES THEREOF (Fri, 29 Jan 2010)
The present invention provides novel compounds of formula (I) and pharmaceutical compositions thereof. The inventive compounds are useful as deacetylase inhibitors (e.g., histone deacetylase inhibitors) and may be useful in the treatment of proliferative diseases such as cancer. In particular, the inventive compounds are HDAC6 inhibitors. The invention also provide synthetic methods for preparing the inventive compounds.
>> read more

DEACETYLASE INHIBITORS AND USES THEREOF (Fri, 29 Jan 2010)
The present invention provides novel compounds of formula (I) and pharmaceutical compositions thereof. The inventive compounds are useful as deacetylase inhibitors (e.g., histone deacetylase inhibitors) and may be useful in the treatment of proliferative diseases such as cancer. In particular, the inventive compounds are HDAC6 inhibitors. The invention also provide synthetic methods for preparing the inventive compounds. </p>
>> read more

SIGNATURES AND PCDETERMINANTS ASSOCIATED WITH PROSTATE CANCER AND METHODS OF USE THEREOF (Fri, 22 Jan 2010)
The present invention provides methods of detecting cancer using biomarkers.
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METHOD FOR PREPARING LARGAZOLE ANALOGS AND USES THEREOF (Fri, 22 Jan 2010)
Analogs of largazole are described herein. Methods of treating cancer and blood disorders using largazole and largazole analogs and pharmaceutical compositions comprising the same are additionally described herein. Methods for preparing largazole analogs are likewise described.
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SIGNATURES AND PCDETERMINANTS ASSOCIATED WITH PROSTATE CANCER AND METHODS OF USE THEREOF (Fri, 22 Jan 2010)
The present invention provides methods of detecting cancer using biomarkers. </p>
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MUC1, CASPASE-8,AND DED-CONTAINING PROTEINS (Fri, 15 Jan 2010)
The disclosure features a variety of compositions and methods for modulating an interaction between MUCl and caspase-8 and/or an interaction between MUCl and a DED- containing protein (e.g., an anti-apoptotic DED-containing protein or a pro-apoptotic DED- containing protein). Such methods and compositions are useful for the treatment or prevention of, e.g., a variety of pathological disorders characterized by elevated or decreased levels of apoptosis. Moreover, the compositions and methods are also useful to identify, design, and generate compounds that modulate the interactions. The compounds and/or pharmaceutical compositions containing the compounds can be used in the treatment of disease.
>> read more

SIGNATURES AND DETERMINANTS ASSOCIATED WITH METASTASIS METHODS OF USE THEREOF (Thu, 31 Dec 2009)
The present invention provides methods of detecting cancer using biomarkers.
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SIGNATURES AND DETERMINANTS ASSOCIATED WITH METASTASIS METHODS OF USE THEREOF (Thu, 31 Dec 2009)
The present invention provides methods of detecting cancer using biomarkers. </p>
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Bifunctional histone deacetylase inhibitors (Fri, 18 Dec 2009)
<p id="p-0001" num="0000">In recognition of the need to develop novel therapeutic agents and efficient methods for the synthesis thereof, the present invention provides novel bifunctional, trifunctional, or multifunctional compounds for inhibiting histone deacetylases, and pharmaceutically acceptable salts and derivatives thereof. The present invention further provides methods for treating disorders regulated by histone deacetylase activity (e.g., proliferative diseases, cancer, inflammatory diseases, protozoal infections, hair loss, etc.) comprising administering a therapeutically effective amount of an inventive compound to a subject in need thereof. The present invention also provides methods for preparing compounds of the invention.</p>
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COMPOUNDS AND COMPOSITIONS USEFUL FOR THE TREATMENT OF MALARIA (Fri, 18 Dec 2009)
The invention provides a class of compounds of formula I, pharmaceutical compositions comprising such compounds and methods of using such compounds to treat or prevent malaria. (I)
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COMPOUNDS AND COMPOSITIONS USEFUL FOR THE TREATMENT OF MALARIA (Fri, 18 Dec 2009)
The invention provides a class of compounds of formula I, pharmaceutical compositions comprising such compounds and methods of using such compounds to treat or prevent malaria. (I) </p>
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COMPOSITIONS AND METHODS FOR INHIBITION OF RETROVIRUSES (Fri, 20 Nov 2009)
Described herein are methods and compositions for the inhibition of retroviral integration and replication. The methods and compositions inhibit the activity of one or more components of the SET complex or base excision repair enzymes and induce autointegration of retroviral double-stranded nucleic acid.
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Histone deacetylase and tubulin deacetylase inhibitors (Fri, 21 Aug 2009)
<p id="p-0001" num="0000">In recognition of the need to develop novel therapeutic agents and efficient methods for the synthesis thereof, the present invention provides novel inhibitors of histone deacetylases, tubulin deacetylases, and/or aggresome inhibitors, and pharmaceutically acceptable salts and derivatives thereof. The inventive compounds fall into two classes—“isotubacin” class and “isoisotubacin” class—all of which include a 1,3-dioxane core. The present invention further provides methods for treating disorders regulated by histone deacetylase activity, tubulin deacetylase activity, and/or the aggresome (e.g., proliferative diseases, cancer, inflammatory diseases, protozoal infections, protein degradation disorders, protein deposition disorders, etc.) comprising administering a therapeutically effective amount of an inventive compound to a subject in need thereof. The present invention also provides methods for preparing compounds of the invention.</p>
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FISH ASSAY FOR EML4 AND ALK FUSION IN LUNG CANCER (Fri, 21 Aug 2009)
Methods and compositions provided relate to conducting a FISH assay for detecting a chromosomal inversion between EML4 and ALK. The FISH assay described herein is useful for diagnostic and prognostic purposes, as well as for determination of therapeutic strategies.
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FISH ASSAY FOR EML4 AND ALK FUSION IN LUNG CANCER (Fri, 21 Aug 2009)
Methods and compositions provided relate to conducting a FISH assay for detecting a chromosomal inversion between EML4 and ALK. The FISH assay de-scribed herein is useful for diagnostic and prognostic pur-poses, as well as for determination of therapeutic strate-gies. </p>
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Conformationally stabilized HIV envelope immunogens and triggering HIV-I envelope to reveal cryptic V3-loop epitopes (Fri, 31 Jul 2009)
<p id="p-0001" num="0000">Stabilized forms of gp120 polypeptide, nucleic acids encoding these stabilized forms, vectors comprising these nucleic acids, and methods of using these polypeptides, nucleic acids, vectors and host cells are disclosed. Crystal structures and computer systems including atomic coordinates for stabilized forms of gp120, and gp120 with an extended V3 loop, and methods of using these structures and computer systems are also disclosed.</p>
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Stabilized alpha helical peptides and uses thereof (Fri, 10 Jul 2009)
<p id="p-0001" num="0000">Novel polypeptides and methods of making and using the same are described herein. The polypeptides include cross-linking (“hydrocarbon stapling”) moieties to provide a tether between two amino acid moieties, which constrains the secondary structure of the polypeptide. The polypeptides described herein can be used to treat diseases characterized by excessive or inadequate cellular death.</p>
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SMALL MOLECULE MYRISTATE INHIBITORS OF BCR-ABL AND METHODS OF USE (Fri, 12 Jun 2009)
The present invention provides novel heteroaryl compounds that are linked to an aryl group via an amine linker. Such compounds are useful for the treatment of cancers. </p>
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Mitochondrial localization of MUC1 (Fri, 29 May 2009)
<p id="p-0001" num="0000">The invention provides methods of identifying and making compounds that inhibit the interaction between MUC1 and either or both of HSP70 and HSP90. Also embraced by the invention are in vivo and in vitro methods of inhibiting such an interaction.</p>
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Methods and compositions relating to promoter regulation by MUC1 and KLF proteins (Fri, 17 Apr 2009)
<p id="p-0001" num="0000">This invention relates to regulation of cell signaling, cell growth, and more particularly to the regulation of cancer or inflammatory cell growth and/or activation. The invention provides methods of, and compositions useful for, inhibiting interactions between MUC1 and a kruppel-like factor (KLF), method of inhibiting interactions between a KLF protein and the p53 promoter, methods of inhibiting the interaction between MUC1 and the p53 promoter, methods of increasing p53 activity, and methods of increasing histone acetylation. The invention also provides screening methods for identifying compounds that inhibit the aforementioned interactions. Pharmaceutical compositions containing the identified compounds can be useful in treating cancers and inflammatory conditions.</p>
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Methods and compositions relating to the regulation of MUC1 by HSF1 and STAT3 (Fri, 10 Apr 2009)
<p id="p-0001" num="0000">This invention relates to regulation of cell signaling, cell growth, and more particularly to the regulation of cancer or inflammatory cell growth and/or activation. The invention provides methods of inhibiting interactions between MUC1 and a heat shock factor, method of inhibiting interactions between transcription factors and the MUC1 promoter, and methods of inhibiting MUC1 expression. The invention also provides screening methods for identifying compounds that inhibit the aforementioned interactions. Pharmaceutical compositions containing the identified compounds can be useful in treating cancers and inflammatory conditions.</p>
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Methods and compositions relating to the regulation of apoptosis by MUC1 and BH3-containing proapoptotic proteins (Fri, 03 Apr 2009)
<p id="p-0001" num="0000">This invention relates to regulation of cell signaling, cell growth, and more particularly to the regulation of cancer or immune cell growth. The invention provides methods of inhibiting interactions between MUC1 and BH3-containing proapoptotic proteins, methods of inhibiting MUC1 expression, and methods of promoting apoptosis. Also provided are screening methods for compounds that inhibit interactions between MUC1 and BH3-containing proapoptotic proteins and pharmaceutical compositions of the same.</p>
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REAGENTS FOR INDUCING AN IMMUNE RESPONSE (Fri, 03 Apr 2009)
The present disclosure relates to reagents (antigenic and/or immunogenic reagents) and kits that are useful in a variety of in vitro, in vivo, and ex vivo methods including, e.g., methods for inducing an immune response, or for generating an antibody, in a subject. The reagents described herein can be used in the treatment or prevention of HIV-1 infections. In addition, the disclosure provides methods and compositions useful for designing (or identifying) an agent that binds to an membrane proximal external region (MPER) of an HIV-1 gp160 polypeptide or an agent that inhibits the fusion of an HIV-1 particle to a cell.
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METHODS AND COMPOSITIONS FOR MODULATING BCL-2 FAMILY POLYPEPTIDES (Fri, 03 Apr 2009)
The present invention is based, at least in part, on the identification of a novel active site on BCL-2 family polypeptide such as BAX, which when bound by a compound, modifies the activity of the BCL-2 family polypeptide.
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REAGENTS FOR INDUCING AN IMMUNE RESPONSE (Fri, 03 Apr 2009)
The present disclosure relates to reagents (antigenic and/or immunogenic reagents) and kits that are useful in a variety of in vitro, in vivo, and ex vivo methods including, e.g., methods for inducing an immune response, or for generating an antibody, in a subject. The reagents described herein can be used in the treatment or prevention of HN-1 infections. In addition, the disclosure provides methods and compositions useful for designing (or identifying) an agent that binds to an membrane proximal external region (MPER) of an HIV-1 gp160 polypeptide or an agent that inhibits the fusion of an HIV-1 particle to a cell. </p>
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METHODS AND COMPOSITIONS FOR MODULATING BCL-2 FAMILY POLYPEPTIDES (Fri, 03 Apr 2009)
The present invention is based, at least in part, on the identification of a novel active site on BCL-2 family polypeptide such as BAX, which when bound by a compound, modifies the activity of the BCL-2 family polypeptide. </p>
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Compositions and methods for identifying transforming and tumor suppressor genes (Fri, 20 Feb 2009)
<p id="p-0001" num="0000">Provided herein are nucleic acids, proteins, vectors, cells, kits, devices and methods useful for identifying regulatable proteins that are able to complement components of cellular signaling pathways. Also provided are compositions and methods using these complementing genes directly as markers for cancer diagnosis or prognosis and as targets for anti-neoplastic therapeutics. Further provided are methods for using changes caused by expression of the complementing genes to indirectly identify associated genes to be used as markers for cancer diagnosis or prognosis and as targets for anti-neoplastic therapeutics.</p>
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ENRICHMENT OF A TARGET SEQUENCE (Fri, 06 Feb 2009)
The present invention is directed to methods, compositions, software and devices for enriching low abundance alleles from a sample. The method is based in part on a modified nucleic acid amplification protocol that includes incubating the reaction mixture at a critical denaturing temperature or 'Tc'. By employing the present invention the current detection limits of all PCR-based technologies are greatly improved.
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ENRICHMENT OF A TARGET SEQUENCE (Fri, 06 Feb 2009)
The present invention is directed to methods, compositions, software and devices for enriching low abundance alleles from a sample. The method is based in part on a modified nucleic acid amplification protocol that includes incubating the reaction mixture at a critical denaturing temperature or "Tc". By employing the present invention the current detection limits of all PCR-based technologies are greatly improved. </p>
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COMPOSITIONS AND METHODS FOR IDENTIFYING TRANSFORMING AND TUMOR SUPPRESSOR GENES (Thu, 01 Jan 2009)
Provided herein are nucleic acids, proteins, vectors, cells, kits, devices and methods useful for identifying regulatable proteins that are able to complement components of cellular signaling pathways. Also provided are compositions and methods using these complementing genes directly as markers for cancer diagnosis or prognosis and as targets for anti-neoplastic therapeutics. Further provided are methods for using changes caused by expression of the complementing genes to indirectly identify associated genes to be used as markers for cancer diagnosis or prognosis and as targets for anti-neoplastic therapeutics.
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PHOSPHORYLATED RALA (Fri, 28 Nov 2008)
Antibodies that are specific for human RalA that is phosphorylated at one or both of Ser183 and Ser194 are described as various methods such antibodies, including diagnostic methods and screening methods.
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Modulation of MUC1 activity (Fri, 21 Nov 2008)
<p id="p-0001" num="0000">The invention provides methods of identifying and making compounds that inhibit the interaction between MUC1 and either p53 or TBP. Also embraced by the invention are in vivo and in vitro methods of inhibiting such an interaction and of inhibiting the expression of MUC1 by a cell.</p>
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A METHOD OF USING PROTEASOME INHIBITORS IN COMBINATION WITH HISTONE DEACETYLASE INHIBITORS TO TREAT CANCER (Fri, 17 Oct 2008)
Disclosed are methods of treating cancer comprising administering to the animal, a therapeutically effective amount of proteasome inhibitors and one or more histone deacetylase inhibitor. The animal is a mammal, preferably a human or a rodent.
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COMPOUNDS AND METHODS FOR ENHANCING MHC CLASS II THERAPIES (Fri, 10 Oct 2008)
The invention provides classes of novel compounds that accelerate peptide loading to DR in the absence of DM and related pharmaceutical compositions. The invention also provides conjugates of these compounds with peptides, antigens or other MHC-based therapeutics, including peptides that self-catalyze their loading onto MHC Class II molecules. Methods are provided for modulating an immune response in a subject. Also disclosed are methods of using the novel compounds, e.g., in combination with MHC-based therapeutics, for the treatment of autoimmune diseases and for the manufacture of medicaments. Methods of improving loading of viral peptides and tumor peptides for enhancing the CD4 T cell response following vaccination against viruses or tumors, and related vaccines, are also provided.
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MUC1-IκB kinase complexes and their activities (Fri, 03 Oct 2008)
<p id="p-0001" num="0000">The disclosure provides methods of identifying and making compounds and pharmaceutical compositions containing the compounds that inhibit the interaction between MUC1 and an IKK. The disclosure also provides in vivo and in vitro methods of inhibiting such an interaction. Also embraced by the disclosure are in vitro and in vivo methods of inhibiting the IKK/NF-κB pathway in cells expressing MUC1. The compounds, compositions, and methods of the disclosure are generally useful in the treatment of various cancers, inflammatory (e.g., autoimmune disorders), and transplant rejection.</p>
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MUC1-IKB KINASE COMPLEXES AND THEIR ACTIVITIES (Fri, 19 Sep 2008)
The disclosure provides methods of identifying and making compounds and pharmaceutical compositions containing the compounds that inhibit the interaction between MUC1 and an IKK. The disclosure also provides in vivo and in vitro methods of inhibiting such an interaction. Also embraced by the disclosure are in vitro and in vivo methods of inhibiting the IKK/NF-&kappav;B pathway in cells expressing MUC1. The compounds, compositions, and methods of the disclosure are generally useful in the treatment of various cancers, inflammatory (e.g., autoimmune disorders), and transplant rejection.
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METHODS AND COMPOSITIONS RELATING TO PROMOTER REGULATION BY MUC1 AND KLF PROTEINS (Fri, 22 Aug 2008)
This invention relates to regulation of cell signaling, cell growth, and more particularly to the regulation of cancer or inflammatory cell growth and/or activation. The invention provides methods of, and compositions useful for, inhibiting interactions between MUCl and a kruppel-like factor (KLF), method of inhibiting interactions between a KLF protein and the p53 promoter, methods of inhibiting the interaction between MUCl and the p53 promoter, methods of increasing p53 activity, and methods of increasing histone acetylation. The invention also provides screening methods for identifying compounds that inhibit the aforementioned interactions. Pharmaceutical compositions containing the identified compounds can be useful in treating cancers and inflammatory conditions.
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METHODS AND COMPOSITIONS RELATING TO THE REGULATION OF APOPTOSIS BY MUC1 AND BH3- CONTAINING PROAPOPTOTIC PROTEINS (Fri, 15 Aug 2008)
This invention relates to regulation of cell signaling, cell growth, and more particularly to the regulation of cancer or immune cell growth. The invention provides methods of inhibiting interactions between MUC1 and BH3 -containing proapoptotic proteins, methods of inhibiting MUC1 expression, and methods of promoting apoptosis. Also provided are screening methods for compounds that inhibit interactions between MUC1 and BH3 -containing proapoptotic proteins and pharmaceutical compositions of the same.
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METHODS AND COMPOSITIONS RELATING TO THE REGULATION OF MUC1 BY HSF1 AND STAT3 (Fri, 15 Aug 2008)
This invention relates to regulation of cell signaling, cell growth, and more particularly to the regulation of cancer or inflammatory cell growth and/or activation. The invention provides methods of inhibiting interactions between MUC1 and a heat shock factor, method of inhibiting interactions between transcription factors and the MUC1 promoter, and methods of inhibiting MUC1 expression. The invention also provides screening methods for identifying compounds that inhibit the aforementioned interactions. Pharmaceutical compositions containing the identified compounds can be useful in treating cancers and inflammatory conditions.
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BIFUNCTIONAL HISTONE DEACETYLASE INHIBITORS (Fri, 01 Aug 2008)
In recognition of the need to develop novel therapeutic agents and efficient methods for the synthesis thereof, the present invention provides novel bifunctional, trifunctional, or multifunctional compounds for inhibiting histone deacetylases, and pharmaceutically acceptable salts and derivatives thereof. The present invention further provides methods for treating disorders regulated by histone deacetylase activity (e.g., proliferative diseases, cancer, inflammatory diseases, protozoal infections, hair loss, etc.) comprising administering a therapeutically effective amount of an inventive compound to a subject in need thereof. The present invention also provides methods for preparing compounds of the invention.
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BIFUNCTIONAL HISTONE DEACETYLASE INHIBITORS (Fri, 01 Aug 2008)
In recognition of the need to develop novel therapeutic agents and efficient methods for the synthesis thereof, the present invention provides novel bifunctional, trifunctional, or multifunctional compounds for inhibiting histone deacetylases, and pharmaceutically acceptable salts and derivatives thereof. The present invention further provides methods for treating disorders regulated by histone deacetylase activity (e.g., proliferative diseases, cancer, inflammatory diseases, protozoal infections, hair loss, etc.) comprising administering a therapeutically effective amount of an inventive compound to a subject in need thereof. The present invention also provides methods for preparing compounds of the invention.</p>
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MUC1 AND GALECTIN-3 (Fri, 20 Jun 2008)
The invention provides methods of identifying and making compounds that inhibit the interaction between MUC1 and galectin-3. Also embraced by the invention are in vivo and in vitro methods of inhibiting such an interaction and of inhibiting the expression of galectin-3 by a cell.
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MUC1 and ABL (Fri, 09 May 2008)
<p id="p-0001-en" num="0000">The present disclosure provides methods of identifying and making compounds and pharmaceutical compositions thereof that inhibit the interaction between MUC1 and Abl. The invention also provides in vivo, in vitro, and ex vivo methods of inhibiting such an interaction. Also featured are in vitro and in vivo methods of stimulating the Abl-dependent apoptotic pathway in cells expressing MUC1. In such methods, the compounds, compositions, and methods described herein are generally useful in the treatment of various cancers. The disclosure also provides methods for inhibiting Abl, and such methods, and compounds and compositions for use in the methods are generally useful for the treatment of cancers, inflammatory conditions, atherosclerotic lesions, and neurologic disorders. </p>
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SMALL MOLECULE PRINTING (Fri, 01 Feb 2008)
The present invention provides compositions and methods to facilitate the identification of compounds that are capable of interacting with a biological macromolecule of interest. In one aspect, a composition is provided that comprises an array of one or more types of chemical compounds attached to a solid support using isocyanate or isothiocyanate chemistry, wherein the density of the array of compounds is at least 1000 spots per cm2. In general, these inventive arrays are generated by: (1) providing a solid support, wherein said solid support is functionalized with an isocyanate or isothiocyanate moiety capable of interacting with a desired chemical compound to form a covalent attachment; (2) providing one or more solutions of one or more types of compounds to be attached to the solid support; (3) delivering said one or more types of compounds to the solid support; and (4) catalyzing the attachment of the compound to the solid support, whereby an array is formed and the array of compounds has a density of at least 1000 spots per cm2. In another aspect, the present invention provides methods for utilizing these arrays to identify small molecule partners for biological macromolecules of interest.
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MUC1 AND ABL (Fri, 01 Feb 2008)
The present disclosure provides methods of identifying and making compounds and pharmaceutical compositions thereof that inhibit the interaction between MUC1 and Abl. The invention also provides in vivo, in vitro, and ex vivo methods of inhibiting such an interaction. Also featured are in vitro and in vivo methods of stimulating the Abl-dependent apoptotic pathway in cells expressing MUC1. In such methods, the compounds, compositions, and methods described herein are generally useful in the treatment of various cancers. The disclosure also provides methods for inhibiting Abl, and such methods, and compounds and compositions for use in the methods are generally useful for the treatment of cancers, inflammatory conditions, atherosclerotic lesions, and neurologic disorders.
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SMALL MOLECULE PRINTING (Fri, 01 Feb 2008)
The present invention provides compositions and methods to facilitate the identification of compounds that are capable of interacting with a biological macromolecule of interest. In one aspect, a composition is provided that comprises an array of one or more types of chemical compounds attached to a solid support using isocyanate or isothiocyanate chemistry, wherein the density of the array of compounds is at least 1000 spots per cm2. In general, these inventive arrays are generated by: (1) providing a solid support, wherein said solid support is functionalized with an isocyanate or isothiocyanate moiety capable of interacting with a desired chemical compound to form a covalent attachment; (2) providing one or more solutions of one or more types of compounds to be attached to the solid support; (3) delivering said one or more types of compounds to the solid support; and (4) catalyzing the attachment of the compound to the solid support, whereby an array is formed and the array of compounds has a density of at least 1000 spots per cm2. In another aspect, the present invention provides methods for utilizing these arrays to identify small molecule partners for biological macromolecules of interest. </p>
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STABILIZED ALPHA HELICAL PEPTIDES AND USES THEREOF (Fri, 28 Dec 2007)
</p> <p>cross-linking ("hydrocarbon stapling") moieties to provide a tether between two amino acid moieties, which constrains the secondary ssttrruuccttuurree ooff tthhee p poollyyppeeppttiidi e. The polypeptides described herein can be used to treat diseases characterized by excessive or inadeauate cellular death.
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HISTONE DEACETYLASE AND TUBULIN DEACETYLASE INHIBITORS (Fri, 16 Nov 2007)
In recognition of the need to develop novel therapeutic agents and efficient methods for the synthesis thereof, the present invention provides novel inhibitors of histone deacetylases, tubulin deacetylases, and/or aggresome inhibitors, and pharmaceutically acceptable salts and derivatives thereof. The inventive compounds fall into two classes ~ "isorubacin" class and "isoisotubacin" class- ~ all of which include a 1,3-dioxane core. The present invention further provides methods for treating disorders regulated by histone deacetylase activity, tubulin deacetylase activity, and/or the aggresome (e.g., proliferative diseases, cancer, inflammatory diseases, protozoal infections, protein degradation disorders, protein deposition disorders, etc.) comprising administering a therapeutically effective amount of an inventive compound to a subject in need thereof. The present invention also provides methods for preparing compounds of the invention.</p>
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CELASTROL, GEDUNIN, AND DERIVATIVES THEREOF AS HSP90 INHIBITORS (Fri, 19 Oct 2007)
Based on the discovery that celastrol and gedunin are Hsp90 inhibitors, the present invention provides novel inhibitors of Hsp90. and pharmaceutically acceptable salts,, derivatives, and compositions thereof. The invention provides two classes of compounds. One class includes celastrol and its derivatives. The other class includes gedunin and its derivatives. The present invention further provides methods for treating disorders wherein Hsρ90 inhibition is desired (e.g., proliferative diseases, cancer, inflammatory diseases, fungal infections, etc.) comprising administering a therapeutically effective amount of an inventive compound to a subject in need thereof. Celastrol, gedunin, and derivatives thereof are particularly useful in the treatment of prostate cancer, breast cancer, ovarian cancer, lung cancer, and leukemia.
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Histone Deacetylase Inhibitors (Fri, 24 Aug 2007)
In recognition of the need to develop novel therapeutic agents, the present invention provides novel histone deacetylase inhibitors. These compounds include an ester bond making them sensitive to deactivation by esterases. Therefore, these compounds are particularly useful in the treatment of skin disorders. When the compounds reaches the bloodstream, an esterase or an enzyme with esterase activity cleaves the compound into biologically inactive fragments or fragments with greatly reduced activity Ideally these degradation products exhibit a short serum and/or systemic half-life and are eliminated rapidly. These compounds and pharmaceutical compositions thereof are particularly useful in treating cutaneous T-cell lymphoma, neurofibromatosis, psoriasis, hair loss, skin pigmentation, and dermatitis, for exmaple. The present invention also provides methods for preparing compounds of the invention and intermediates thereto.
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HISTONE DEACETYLASE INHIBITORS (Fri, 24 Aug 2007)
In recognition of the need to develop novel therapeutic agents, the present invention provides novel histone deacetylase inhibitors. These compounds include an ester bond making them sensitive to deactivation by esterases. Therefore, these compounds are particularly useful in the treatment of skin disorders. When the compounds reaches the bloodstream, an esterase or an enzyme with esterase activity cleaves the compound into biologically inactive fragments or fragments with greatly reduced activity Ideally these degradation products exhibit a short serum and/or systemic half-life and are eliminated rapidly. These compounds and pharmaceutical compositions thereof are particularly useful in treating cutaneous T-cell lymphoma, neurofibromatosis, psoriasis, hair loss, skin pigmentation, and dermatitis, for exmaple. The present invention also provides methods for preparing compounds of the invention and intermediates thereto.</p>
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Methods of identifying agents which enhance caspase activity (Wed, 25 Jul 2007)
<p id="p-0001-en" num="0000">Methods for identifying agents which enhance the activity of a caspase according to the invention are described, as well as methods for enhancing caspase activity and methods for enhancing apoptosis in a lymphocyte.</p>
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HIV GP120 CRYSTAL STRUCTURE AND ITS USE TO IDENTIFY IMMUNOGENS (Fri, 16 Mar 2007)
The present disclosure relates to stabilized forms of the HIV gpl20 envelope protein in complex with the broadly neutralizing CD4-binding site antibody bl2, to crystalline forms of the stabilized forms of the HIV gpl20 envelope protein in complex with the broadly neutralizing CD4- binding site antibody b 12, and to the high resolution structure obtained from these crystals by X-ray diffraction methods. Methods for identifying immunogenic polypeptides based on these structures are also disclosed.
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CONFORMATIONALLY STABILIZED HIV ENVELOPE IMMUNOGENS AND TRIGGERING HIV-1 ENVELOPE TO REVEAL CRYPTIC V3-LOOP EPITOPES (Fri, 16 Mar 2007)
Stabilized forms of gpl20 polypeptide, nucleic acids encoding these stabilized forms, vectors comprising these nucleic acids, and methods of using these polypeptides, nucleic acids, vectors and host cells are disclosed. Crystal structures and computer systems including atomic coordinates for stabilized forms of gpl20, and gpl20 with an extended V3 loop, and methods of using these structures and computer systems are also disclosed.
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MITOCHONDRIAL LOCALIZATION OF MUC1 (Fri, 02 Mar 2007)
The invention provides methods of identifying and making compounds that inhibit the interaction between MUCl and either or both of HSP70 and HSP90. Also embraced by the invention are in vivo and in vitro methods of inhibiting such an interaction.
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MODULATION OF MUC1-DEPENDENT ANTI-ESTROGEN RESISTANCE (Fri, 01 Dec 2006)
The present invention provides methods for identification and use of compounds that modulate the association of MUC1 with estrogen receptors and thereby antagonize MUC1-related resistance to anti-estrogen treatment.
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MODULATION OF MUC1-DEPENDENT ANTI-ESTROGEN RESISTANCE (Fri, 01 Dec 2006)
The present invention provides methods for identification and use of compounds that modulate the association of MUC1 with estrogen receptors and thereby antagonize MUC1-related resistance to anti-estrogen treatment. </p>
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MODULATION OF MUC1 ACTIVITY (Fri, 25 Aug 2006)
The invention provides methods of identifying and making compounds that inhibit the interaction between MUCl and either p53 or TBP. Also embraced by the invention are in vivo and in vitro methods of inhibiting such an interaction and of inhibiting the expression of MUCl by a cell.
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MODULATION OF MUC1 ACTIVITY (Fri, 25 Aug 2006)
The invention provides methods of identifying and making compounds that inhibit the interaction between MUCl and either p53 or TBP. Also embraced by the invention are in vivo and in vitro methods of inhibiting such an interaction and of inhibiting the expression of MUCl by a cell. </p>
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STABILIZED ALPHA HELICAL PEPTIDES AND USES THEREOF (Thu, 20 Jul 2006)
Novel polypeptides and methods of making and using the same are described herein. The polypeptides include cross-linking (“hydrocarbon stapling”) moieties to provide a tether between two amino acid moieties, which constrains the secondary structure of the polypeptide. The polypeptides described herein can be used to treat diseases characterized by excessive or inadequate cellular death.
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Chemokine N-terminal deletion mutations (Thu, 20 Apr 2006)
The invention relates to mutant chemokines and pharmaceutical compositions thereof, wherein the mutant inhibits the corresponding endogenous chemokine from binding or activating a responsive receptor. The claimed mutant chemokines can be administered to a patient for the treatment of prophylaxis of a chemokine-mediated disease. The invention further relates to isolated DNAs encoding the mutant chemokines, vectors and recombinant host cells containing the same.
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Stabilized alpha helical peptides and uses thereof (Fri, 11 Nov 2005)
<p id="p-0001-en" num="0000">Novel polypeptides and methods of making and using the same are described herein. The polypeptides include cross-linking (“hydrocarbon stapling”) moieties to provide a tether between two amino acid moieties, which constrains the secondary structure of the polypeptide. The polypeptides described herein can be used to treat diseases characterized by excessive or inadequate cellular death.</p>
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STABILIZED ALPHA HELICAL PEPTIDES AND USES THEREOF (Fri, 20 May 2005)
Novel polypeptides and methods of making and using the same are described herein. The polypeptides include cross-linking (“hydrocarbon stapling”) moieties to provide a tether between two amino acid moieties, which constrains the secondary structure of the polypeptide. The polypeptides described herein can be used to treat diseases characterized by excessive or inadequate cellular death.
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STABILIZED ALPHA HELICAL PEPTIDES AND USES THEREOF (Fri, 20 May 2005)
Novel polypeptides and methods of making and using the same are described herein. The polypeptides include cross-linking (~hydrocarbon stapling~) moieties to provide a tether between two amino acid moieties, which constrains the secondary structure of the polypeptide. The polypeptides described herein can be used to treat diseases characterized by excessive or inadequate cellular death. </p>
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STABILIZED ALPHA HELICAL PEPTIDES AND USES THEREOF (Fri, 20 May 2005)
Novel polypeptides and methods of making and using the same are described herein. The polypeptides include cross-linking ("hydrocarbon stapling") moieties to provide a tether between two amino acid moieties, which constrains the secondary structure of the polypeptide. The polypeptides described herein can be used to treat diseases characterized by excessive or inadequate cellular death. </p>
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Computer-based methods of designing molecules (Fri, 21 Jan 2005)
<p id="p-0001" num="0000">The invention features a method of generating an immunogenic compound with the ability to induce an immune response to a molecule produced by a pathogenic agent, e.g., a infectious agent or a tumor cell. Also included in the invention are an immunogenic compound generated by the method of the invention and a method of inducing an immune response in a mammal that involves administering the immunogenic compound to the mammal.</p>
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Pharmaceutically active compounds and methods of use thereof (Fri, 03 Dec 2004)
<p id="p-0001-en" num="0000">The present invention relates to dihydrofolate reductase inhibitors having an aromatic group and a heteroaromatic group linked by a methylene group; and methods of treatment and pharmaceutical compositions that utilize or comprise one or more of such dihydrofolate reductase inhibitors.</p>
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PHARMACEUTICALLY ACTIVE ORNITHINE DERIVATIVES, AMMONIUM SALTS THEREOF AND METHODS OF MAKING SAME (Fri, 05 Nov 2004)
The present invention relates to pharmaceutically active ornithine compounds, particularly to pharmaceutically acceptable ammonium salts of Nδ-acyl derivatives of Nα(4-amino-4-deoxypteroyl)-L-ornithine compounds; and methods of treatment and pharmaceutical compositions that utilize or comprise one or more of such ammonium salts. The ammonium salts provided by the invention exhibit superior chemical stability than corresponding acidic Nδ-acyl derivatives of Nα(4-amino-4-deoxypteroyl)-L-ornithine compounds.
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PHARMACEUTICALLY ACTIVE ORNITHINE DERIVATIVES, AMMONIUM SALTS THEREOF AND METHODS OF MAKING SAME (Fri, 05 Nov 2004)
The present invention relates to pharmaceutically active ornithine compounds, particularly to pharmaceutically acceptable ammonium salts of N.delta.-acyl derivatives of N.alpha.(4-amino-4-deoxypteroyl)-L-ornithine compounds; and methods of treatment and pharmaceutical compositions that utilize or comprise one or more of such ammonium salts. The ammonium salts provided by the invention exhibit superior chemical stability than corresponding acidic N.delta.-acyl derivatives of N.alpha.(4-amino-4-deoxypteroyl)-L-ornithine compounds. </p>
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MODULATION OF MUC1 MEDIATED SIGNAL TRANSDUCTION (Fri, 29 Oct 2004)
The present invention provides compositions and methods for inhibiting the binding of the carboxy-terminus of MUC1 to PDZ domain(s) and to enhance the sensitivity of MUC1 expressing cancer cells to chemotherapeutic agents.
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GENE EXPRESSION IN BREAST CANCER (Fri, 08 Oct 2004)
The invention features nucleic acids encoding proteins that are expressed at a higher or a lower level in breast cancer cells than in normal breast cells or in a cell of one grade or stage of breast cancer than in a cell of another grade or stage of breast cancer. The invention also includes proteins encoded by the nucleic acids, vectors containing the nucleic acids, and cells containing the vectors. In another aspect, the invention features methods of diagnosing and treating breast cancers of various grades and stages. </p>
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2,4-DIAMINO-5-[5’-SUBSTITUTED-BENZYL] PYRIMIDINES AND 2,4-DIAMINO-6-[5’-SUBSTITUTED-BENZYL] QUINAZOLINES (Fri, 01 Oct 2004)
The present invention relates to dihydrofolate reductase inhibitors having an aromatic group and a heteroaromatic group linked by a methylene group; and methods of treatment and pharmaceutical compositions that utilize or comprise one or more of such dihydrofolate reductase inhibitors. More particularly, the present invention relates to dihydrofolate reductase inhibitors having a substituted aromatic group and a heteroaromatic group linked by a methylene group wherein at least one of the aromatic group substituents is a lipophilic residue comprising at least one acidic functional group.
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Pharmaceutically active ornithine derivatives, ammonium salts thereof and methods of making same (Fri, 16 Apr 2004)
<p id="p-0001-en" num="0000">In one embodiment, the present invention relates to a new class of ammonium salts of N<sup>δ</sup>-acyl derivatives of N<sup>α</sup>-(4-amino-4-deoxypteroyl)-L-ornithine compounds having a structure according to formula II-IV.</p> <p id="p-0002-en" num="0000">Formula II has the structure of: <chemistry id="chem-us-00001-en" num="00001"><img id="emi-c00001-en" he="41.15mm" wi="75.52mm" file="US06989386-20060124-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/></chemistry><ul id="ul0001-en" list-style="none"><li><ul id="ul0002-en" list-style="none"><li>wherein:</li><li>R<sup>2 </sup>represents up to four groups independently selected at each occurrence of R<sup>2 </sup>from the group consisting of hydrogen, C<sub>1-6 </sub>alkyl, C<sub>2-6 </sub>alkenyl, C<sub>2-6 </sub>alkynyl, C<sub>3-8 </sub>cycloalkyl, C<sub>1-6 </sub>alkoxy, chloro, fluoro, hydroxy, and —COOH;</li><li>R<sup>3</sup>, R<sup>4</sup>, and R<sup>5 </sup>are each independently selected from hydrogen and C<sub>1-6 </sub>alkyl; or NR<sup>3</sup>R<sup>4 </sup>taken combination can form a 5 to 7 member heterocycle having at least one nitrogen ring atom; and</li><li>x is a real number greater than 0 and less than about 4.</li></ul></li></ul></p> <p id="p-0003-en" num="0000">The ammonium salts provided by the invention exhibit high inhibitory activity against the growth o methotrexate-resistant cells, and also exhibit superior chemical stability than corresponding acidic N<sup>δ</sup>-acyl derivatives of N<sup>δ</sup>-acyl derivatives of N<sup>α</sup>(4-amino-4-deoxypteroyl)-L-ornithine compounds.</p>
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Antiviral compounds and methods of administration (Wed, 04 Feb 2004)
<p id="p-00001-en">The invention provides lipophilic phosphonoacid/nucleoside conjugates that exhibit exceptional antiviral activity, including activity against drug-resistant HIV strains. Compounds of the invention include phosphonoacid/nucleoside conjugates where the carboxyl group and phosphonyl groups of the phosphonacid are esterified whereby the compound contains at least one lipophilic group and at least one nucleoside group.</p>
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DENTRITIC CELL NODES (Fri, 05 Dec 2003)
The present invention features dentritic cell nodes that can be used to vaccinate subjects against pathogens and to modulate a subject~s immune system to treat or prevent various diseases and conditions. </p>
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CARCINOEMBRYONIC ANTIGEN CELL ADHESION MOLECULE 1 (CEACAM1) STRUCTURE AND USES THEREOF IN DRUG IDENTIFICATION AND SCREENING (Fri, 24 Oct 2003)
Disclosed in the first crystal structure in the carcinoembryonic antigen (CEA) family, the mouse CEACAM1 a [1,4], containing the N-terminal functional domain that is characterized as having a uniquely folded CC' loop. This novel feature could not be predicted based on sequence analysis alone. The structure has provided a prototypic architecture for modeling human homologues within the CEA family. These tertiary structures are used in a number of screening methods for identifying candidate molecules that have a binding affinity for the tertiary structure of the CC' loop and its vicinity. Pharmaceutical preparations that include one or more of such identified candidates may then be provided and used in treatments for certain bacterial and viral infections, certain tumors and disorders of angiogenesis or immune responses and autoimmune disease.
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PHARMACEUTICALLY ACTIVE COMPOUNDS AND METHODS OF USE THEREOF (Sat, 31 May 2003)
The present invention relates to dihydrofolate reductase inhibitors having an aromatic group and a heteroaromatic group linked by a methylene group; and methods of treatment and pharmaceutical compositions that utilize or comprise one or more of such dihydrofolate reductase inhibitors.
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Polypeptides and methods for thymic vaccination (Fri, 02 May 2003)
<p id="p-a-0001-en">Methods of thymic vaccination are described, in which a polypeptide of interest is administered and which allows positive or negative selection of a T cell receptor (TCR) specificity in the thymus, to retain a desired specificity (positive) or to eliminate an undesired specificity (negative) at the level of TCR repertoire development, in order to generate TCRs which are designed to recognize disease antigens or foreign antigens, such as to treat or prevent cancers, autoimmune diseases, infections, or effects of biological warfare agents. </p>
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COMPUTER-BASED METHODS OF DESIGNING MOLECULES (Fri, 28 Feb 2003)
The invention features a method of generating an immunogenic compound with the ability to induce an immune response to a molecule produced by a pathogenic agent, e.g., a infectious agent or a tumor cell. Also included in the invention are an immunogenic compound generated by the method of the invention and a method of inducing an immune response in a mammal that involves administering the immunogenic compound to the mammal.
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COMPUTER-BASED METHODS OF DESIGNING MOLECULES (Fri, 28 Feb 2003)
The invention features a method of generating an immunogenic compound with the ability to induce an immune response to a molecule produced by a pathogenic agent, e.g., a infectious agent or a tumor cell. Also included in the invention are an immunogenic compound generated by the method of the invention and a method of inducing an immune response in a mammal that involves administering the immunogenic compound to the mammal. </p>
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Mutation scanning array, and methods of use thereof (Fri, 25 Oct 2002)
<p id="p-0001-en" num="0000">The present method is directed to using a mutation scanning array to identify mismatches or polymorphisms in multiple genes or the same gene in multiple individuals. The array can be a chip or a microsphere. Preferably, the array has elements containing immobilized oligonucleotides that collectively span at least 10 different whole genes.</p>
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Cloning and characterization of a CD2 binding protein (CD2BP2) (Fri, 13 Sep 2002)
<p id="p-0001-en" num="0000">A human CD2 cytoplasmic tail binding protein, CD2BP2, is described, as well as the nucleic acids encoding the protein. Also described are expression vectors and recombinant host cells comprising nucleic acids encoding the CD2BP2 protein, and methods of use for the CD2BP2 protein and nucleic acids encoding the CD2BP2 protein.</p>
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POLYPETPTIDES AND METHODS FOR THYMIC VACCINATION (Fri, 01 Jun 2001)
Methods of thymic vaccination are described, in which a polypeptide of interest is administered and which allows positive or negative selection of a T cell receptor (TCR) specificity in the thymus, to retain a desired specificity (positive) or to eliminate an undesired specificity (negative) at the level of TCR repertoire development, in order to generate TCRs which are designed to recognize disease antigens or foreign antigens, such as to treat or prevent cancers, autoimmune diseases, infections, or effects of biological warfare agents.
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POLYPEPTIDES AND METHODS FOR THYMIC VACCINATION (Fri, 01 Jun 2001)
Methods of thymic vaccination are described, in which a polypeptide of interest is administered and which allows positive or negative selection of a T cell receptor (TCR) specificity in the thymus, to retain a desired specificity (positive) or to eliminate an undesired specificity (negative) at the level of TCR repertoire development, in order to generate TCRs which are designed to recognize disease antigens or foreign antigens, such as to treat or prevent cancers, autoimmune diseases, infections, or effects of biological warfare agents. </p>
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CANCER IMMUNOTHERAPY AND DIAGNOSIS USING CYTOCHROME P450 1B1 (Sat, 26 May 2001)
The invention provides methods for conducting cancer immunotherapy and diagnosis using cytochrome P450 1B1 and peptide fragments thereof. </p>
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Method for identifying mismatch repair glycosylase reactive sites, compounds and uses thereof (Wed, 17 Jan 2001)
<p id="p-00001-en">The present application discloses a method of identifying mutations in a target DNA sequence. The method involves:</p> <p id="p-00002-en">(a) hybridizing the target DNA sequence with a control DNA sequence wherein said control DNA sequence is the wild-type DNA sequence corresponding to the target DNA sequence to create a duplex;</p> <p id="p-00003-en">(b) treating the duplex to remove any spontaneous aldehydes;</p> <p id="p-00004-en">(c) reacting the duplex with a repair glycosylase to convert any mismatched sites in the duplex to reactive sites containing an aldehyde-containing abasic site;</p> <p id="p-00005-en">(d) reacting the duplex with a compound of the formula X-Z-Y, wherein X is a detectable moiety, Y is NHNH<sub>2</sub>, O—NH<sub>2</sub>or NH<sub>2</sub>, and Z is a hydrocarbon, alkyhydroxy, alkylethoxy, alkylester, alkylether, alkylamide or alkylamine, wherein Z may be substituted or unsubstituted; and wherein Z may contain a cleavable group; for a sufficient time and under conditions to covalently bind to the reactive sites;</p> <p id="p-00006-en">(e) detecting the bound compound to identify sites of mismatches;</p> <p id="p-00007-en">(f) determining where the mismatch occurs; and</p> <p id="p-00008-en">(g) determining whether the mismatch is a mutation or polymorphisms.</p>
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PHARMACEUTICALLY ACTIVE COMPOUNDS AND METHODS OF USE THEREOF (Fri, 13 Oct 2000)
The invention relates to pharmaceutically active compounds, and methods of treatment and pharmaceutical compositions that utilize or comprise one or more such compounds. Compounds of the invention are particularly useful for the treatment or prophylaxis of diseases associated with parasitic infection such as toxoplasmosis, cryptosporidiosis, leischmaniasis and malaria.
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PHARMACEUTICALLY ACTIVE COMPOUNDS AND METHODS OF USE THEREOF (Fri, 13 Oct 2000)
The invention relates to pharmaceutically active compounds, and methods of treatment and pharmaceutical compositions that utilize or comprise one or more such compounds. Compounds of the invention are particularly useful for the treatment or prophylaxis of diseases associated with parasitic infection such as toxoplasmosis, cryptosporidiosis, leischmaniasis and malaria. </p>
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MUTATION SCANNING ARRAY, AND METHODS OF USE THEREOF (Fri, 07 Jul 2000)
The present method is directed to using a mutation scanning array to identify mismatches or polymorphisms in multiple genes or the same gene in multiple individuals. The array can be a chip or a microsphere. Preferably, the array has elements containing immobilized oligonucleotides that collectively span at least 10 different whole genes.
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MUTATION SCANNING ARRAY, AND METHODS OF USE THEREOF (Fri, 07 Jul 2000)
The present method is directed to using a mutation scanning array to identify mismatches or polymorphisms in multiple genes or the same gene in multiple individuals. The array can be a chip or a microsphere. Preferably, the array has elements containing immobilized oligonucleotides that collectively span at least 10 different whole genes. </p>
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CLONING AND CHARACTERIZATION OF A CD2 BINDING PROTEIN (CD2BP2) (Fri, 16 Jun 2000)
A human CD2 cytoplasmic tail binding protein, CD2BP2, is described, as well as the nucleic acids encoding the protein. Also described are expression vectors and recombinant host cells comprising nucleic acids encoding the CD2BP2 protein, and methods of use for the CD2BP2 protein and nucleic acids encoding the CD2BP2 protein.
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Siva genes, novel genes involved in CD27-mediated apoptosis (Wed, 05 Jan 2000)
<p>The invention provides isolated nucleic acids molecules, designated Siva nucleic acid molecules, which encode proteins involved in immune cell apoptosis. The invention also provides antisense nucleic acid molecules, recombinant expression vectors containing Siva nucleic acid molecules, host cells into which the expression vectors have been introduced, and nonhuman transgenic animals in which a Siva gene has been introduced or disrupted. The invention still further provides isolated Siva proteins, fusion proteins, antigenic peptides and anti-Siva antibodies. Diagnostic, screening, and therapeutic methods utilizing compositions of the invention are also provided.</p>
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METHOD FOR IDENTIFYING MISMATCH REPAIR GLYCOSYLASE REACTIVE SITES, COMPOUND AND USES THEREOF_____________________________________ (Fri, 27 Aug 1999)
The present application discloses a method of identifying mutations in a target DNA sequence. The method involves: (a) hybridizing the target DNA sequence with a control DNA sequence wherein said control DNA sequence is the wild-type DNA sequence corresponding to the target DNA sequence to create a duplex; (b) treating the duplex to remove any spontaneous aldehydes; (c) reacting the duplex with a repair glycosylase to convert any mismatched sites in the duplex to reactive sites containing an aldehyde-containing abasic site; (d) reacting the duplex with a compound of the formula X-Z-Y, wherein X is a detectable moiety, Y is NHNH2, O-NH2 or NH2, and Z is a hydrocarbon, alkylhydroxy, alkylethoxy, alkylester, alkylether, alkylamide or alkylamine, wherein Z may be substituted or unsubstituted; and wherein Z may contain a cleavable group; for a sufficient time and under conditions to covalently bind to the reactive sites; (e) detecting the bound compound to identify sites of mismatches; (f) determining where the mismatch occurs; and (g) determining whether the mismatch is a mutation or polymorphisms.
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METHOD FOR IDENTIFYING MISMATCH REPAIR GLYCOSYLASE REACTIVE SITES, COMPOUND AND USES THEREOF (Fri, 27 Aug 1999)
The present application discloses a method of identifying mutations in a target DNA sequence. The method involves: (a) hybridizing the target DNA sequence with a control DNA sequence wherein said control DNA sequence is the wild-type DNA sequence corresponding to the target DNA sequence to create a duplex; (b) treating the duplex to remove any spontaneous aldehydes; (c) reacting the duplex with a repair glycosylase to convert any mismatched sites in the duplex to reactive sites containing an aldehyde-containing abasic site; (d) reacting the duplex with a compound of the formula X-Z-Y, wherein X is a detectable moiety, Y is NHNH2, O-NH2 or NH2, and Z is a hydrocarbon, alkylhydroxy, alkylethoxy, alkylester, alkylether, alkylamide or alkylamine, wherein Z may be substituted or unsubstituted; and wherein Z may contain a cleavable group; for a sufficient time and under conditions to covalently bind to the reactive sites; (e) detecting the bound compound to identify sites of mismatches; (f) determining where the mismatch occurs; and (g) determining whether the mismatch is a mutation or polymorphisms. </p>
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MONOVALENT, MULTIVALENT, AND MULTIMERIC MHC BINDING DOMAIN FUSION PROTEINS AND CONJUGATES, AND USES THEREFOR (Fri, 27 Aug 1999)
The present invention is directed to the field of immunology. In particular, the present invention is directed to the design, production, and use of monovalent, multivalent and multimeric Major Histocompatibility Complex binding domain fusion proteins and conjugates. </p>
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Chemokine N-terminal deletion mutations (Wed, 30 Dec 1998)
<p>The invention relates to mutant chemokines and pharmaceutical compositions thereof, wherein the mutant inhibits the corresponding endogenous chemokine from binding or activating a responsive receptor. The claimed mutant chemokines can be administered to a patient for the treatment or prophylaxis of a chemokine-mediated disease. The invention further relates to isolated DNAs encoding the mutant chemokines, vectors and recombinant host cells containing the same. -GOVT PAC GOVERNMENT SUPPORT PAR The invention described herein was supported in whole or in part by Grant No.: CA53091 from the National Institutes of Health. The Government has certain rights in the invention.</p>
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THE SIVA GENES INVOLVED IN CD27-MEDIATED APOPTOSIS (Fri, 04 Dec 1998)
The invention provides isolated nucleic acids molecules, designated Siva nucleic acid molecules, which encode proteins involved in immune cell apoptosis. The invention also provides antisense nucleic acid molecules, recombinant expression vectors containing Siva nucleic acid molecules, host cells into which the expression vectors have been introduced, and non human transgenic animals in which a Siva gene has been introduced or disrupted. The invention still further provides isolated Siva proteins, fusion proteins, antigenic peptides and anti-Siva antibodies. Diagnostic, screening, and therapeutic methods utilizing compositions of the invention are also provided.
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Combination of herpes simplex virus and chemotherapy for treating cancer (Thu, 10 Sep 1998)
The present invention is directed to novel methods of enhancing the effectiveness of DNA damaging agents by exposing cells to viruses prior to or during exposure to the damaging agent. In certain embodiments of the invention, the DNA damaging agent is ionizing radiation, the virus is an adenovirus, and the increase in cell killing is synergistic when compared to radiation alone.
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ANTIVIRAL PHOSPHONATE PRODRUGS OF NUCLEOSIDES AND NUCLEOSIDE ANALOGUES (Fri, 04 Sep 1998)
The invention provides lipophilic phosphonoacid/nucleoside conjugates that exhibit exceptional antiviral activity, including activity against drug-resistant HIV strains. Compounds of the invention include phosphonoacid/nucleoside conjugates where the carboxyl group and phosphonyl groups of the phosphonacid are esterified whereby the compound contains at least one lipophilic group and at least one nucleoside group.
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THYMOCYTE CASPASE ACTIVITY AND NEGATIVE SELECTION (Fri, 21 Aug 1998)
Work described herein shows that T cell receptor triggering by peptide/MHC ligands activates a caspase in thymocytes, including CD4+CD8+ double positive thymocytes, resulting in their death. Methods of inhibiting apoptosis in thymocytes are described, as well as assays for identifying an agent which alters the activity of the caspase are described.
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Chemokine N-terminal deletion mutations (Wed, 15 Apr 1998)
<p>The invention relates to mutant chemokines and pharmaceutical compositions thereof, wherein the mutant inhibits the corresponding endogenous chemokine from binding or activating a responsive receptor. The claimed mutant chemokines can be administered to a patient for the treatment or prophylaxis of a chemokine-mediated disease. The invention further relates to isolated DNAs encoding the mutant chemokines, vectors and recombinant host cells containing the same. -GOVT PAC GOVERNMENT SUPPORT PAR The invention described herein was supported in whole or in part by Grant No.: CA53091 from the National Institutes of Health. The Government has certain rights in the invention.</p>
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Chemokine N-terminal deletion mutations (Wed, 07 Jan 1998)
<p>The invention relates to mutant chemokines and pharmaceutical compositions thereof, wherein the mutant inhibits the corresponding endogenous chemokine from binding or activating a responsive receptor. The claimed mutant chemokines can be administered to a patient for the treatment or prophylaxis of a chemokine-mediated disease. The invention further relates to isolated DNAs encoding the mutant chemokines, vectors and recombinant host cells containing the same. -GOVT PAC GOVERNMENT SUPPORT PAR The invention described herein was supported in whole or in part by Grant No.: CA53091 from the National Institutes of Health. The Government has certain rights in the invention.</p>
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CHEMOKINE N-TERMINAL DELETION MUTATIONS (Fri, 06 Dec 1996)
The invention relates to mutant chemokines and pharmaceutical compositions thereof, wherein the mutant inhibits the corresponding endogenous chemokine from binding or activating a responsive receptor. The claimed mutant chemokines can be administered to a patient for the treatment or prophylaxis of a chemokine-mediated disease. The invention further relates to isolated DNAs encoding the mutant chemokines, vectors and recombinant host cells containing the same.
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CHEMOKINE N-TERMINAL DELETION MUTATIONS (Fri, 06 Dec 1996)
The invention relates to mutant chemokines and pharmaceutical compositions thereof, wherein the mutant inhibits the corresponding endogenous chemokine from binding or activating a responsive receptor. The claimed mutant chemokines can be administered to a patient for the treatment or prophylaxis of a chemokine-mediated disease. The invention further relates to isolated DNAs encoding the mutant chemokines, vectors and recombinant host cells containing the same. </p>
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1,2-benzoquinones and methods for making and using same (Wed, 27 Mar 1996)
<p>The present invention relates to 1,2-benzoquinones; methods of preparation of 1,2-benzoquinones that include preparation of 4,5-substituted-1,2-benzoquinones in a one-pot reaction; and methods of treatment and pharmaceutical compositions that utilize or comprise one or more of such benzoquinones.</p>
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1,2-BENZOQUINONES (Fri, 03 Feb 1995)
The present invention relates to 1,2-benzoquinones; methods of preparation of 1,2-benzoquinones that include preparation of 4,5-substituted- 1,2-benzoquinones in a one-pot reaction; and methods of treatment and pharmaceutical compositions that utilize or comprise one or more of such benzoquinones.
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2-aza-2-desamino analogues of 5,8-dideazafolic acid (Wed, 11 Aug 1993)
<p>2-Aza-2-desamino analogues of 5,8-dideazafolic acid, which analogues have the formula ##STR1## wherein X is an aryl or heteroaryl moiety; PA1 R.sup.1 is H, C.sub.1 -C.sub.4 alkyl, C.sub.3 -C.sub.4 alkenyl, or C.sub.3 -C.sub.4 alkynyl; and PA1 R.sup.2 is OH, an L-.alpha.-amino acid, or a peptide comprising L-.alpha.-amino acids. -GOVT PAR This invention was made in the course of work supported in part by the U.S. Government, which therefore has certain rights in the invention.</p>
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2-AZA-2-DESAMINO ANALOGUES OF 5,8-DIDEAZAFOLIC ACID (Fri, 05 Mar 1993)
2-Aza-2-desamino analogues of 5,8-dideazafolic acid, which analogues have formula (I), wherein x is an aryl or heteroaryl moiety; R1 is H, C¿1?-C4 alkenyl, or C3-C4 alkenyl; and R?2¿ is OH, an L-α-amino acid, or a peptide comprising L-α-amino acids.
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Dideoxynucleoside-5'-phosphonoformic acid compounds (Wed, 22 Jul 1992)
<p>Compounds having the structure ##STR1## in which R is alkyl, aryl, or aralkyl, A is hydrogen or a water-soluble cation, B is hydrogen, fluorine, or azido, the bond is saturated when B is fluorine or azido and is saturated or unsaturated when B is hydrogen, and D is a purine or pyrimidine base are effective inhibitors of retrovirus replication. -GOVT PAR This invention was made with government support and the Federal government has certain rights in the invention.</p>
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COMPLEX OF DIDEOXYNUCLEOSIDE AND PHOSPHONOFORMIC ACID (Thu, 14 Nov 1991)
Compounds having the structure <CHEM> in which R is alkyl, aryl, or aralkyl, A is hydrogen or a water-soluble cation, B is hydrogen, fluorine, or azido, the bond --- is saturated when B is fluorine or azido and is saturated or unsaturated when B is hydrogen, and D is a purine or pyrimidine base are effective inhibitors of retorvirus replication. <IMAGE>
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Platinum complexes of azodiazonium dyes as anti-tumor agents (Wed, 16 Jan 1991)
<p>Complexes having the structure ##STR1## in which R, R.sub.1, R.sub.2, R.sub.3 represent lower alkyl groups are cytotoxic to tumor cells in mammals and enhance the killing effect of radiation and heat. -GOVT PAR This invention was made with Government support and the Federal Government has certain rights in the invention.</p>
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Desamino-aminopterin and -methotrexate (Wed, 12 Sep 1990)
<p>A compound having the structure ##STR1## in which R.sub.1 is hydrogen or a lower alkyl group and R.sub.2 is hydrogen or methyl. -GOVT PAR This invention was made with Government support and the Government has certain rights in the invention.</p>
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DESAMINO-AMINOPTERIN AND -METHOTREXATE (Fri, 04 May 1990)
A compound having structure (I), in which R1 is hydrogen or a lower alkyl group and R2 is hydrogen or methyl.
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Acid-cleavable compound (Wed, 17 Aug 1988)
<p>Heterobifunctional reagents that are cleavable under mildly acidic conditions are disclosed. The reagents include an acid cleavable cyclohexene-1,2,-dicarboxylic acid monoamide group. Also disclosed are methods of making the cross-linkers, as well as methods of using the cross-linkers, e.g., to deliver a biologically active substance across the membranes of selected cells in a heterogeneous cell population; once inside the cell the active substance is released, intact, by the transient, mild acidity of certain cell structures. Finally, a method of characterizing complex multi-chain protein structures is disclosed. -GOVT PAR This invention was made with Government support. The Government has certain rights in this invention.</p>
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Cell-delivery agent (Wed, 26 Nov 1986)
<p>A photo-cleavable compound for delivery and release of a biologically active substance to selected target cells; the compound includes a binding partner for a specific cell-surface receptor of those target cells, the biologically active substance to be delivered, and a photo-cleavable bridge between the binding partner and the biologically active substance. When the compound is exposed to a heterogeneous population of target and non-target cells, it binds selectively to the receptors on the surface of the target cells. Exposing the compound to light of selected wave length cleaves it, yielding the active substance. -GOVT PAR This invention was made with Government support. The Government has certain rights in this invention.</p>
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CELL-DELIVERY AGENT (Thu, 03 Jul 1986)
A photo-cleavable compound for delivery and release of a biologically active substance to selected target cells; the compound includes a binding partner for a specific cell-surface receptor of those target cells, the biologically active substance to be delivered, and a photo-cleavable bridge between the binding partner and the biologically active substance. When the compound is exposed to a heterogeneous population of target and non-target cells, it binds selectively to the receptors on the surface of the target cells. Exposing the compound to light of selected wave length cleaves it, yielding the active substance.
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CELL-DELIVERY AGENT (Fri, 31 Jan 1986)
A photo-cleavable compound for delivery and release of a biologically active substance to selected target cells; the compound includes a binding partner for a specific cell-surface receptor of those target cells, the biologically active substance to be delivered, and a photo-cleavable bridge between the binding partner and the biologically active substance. When the compound is exposed to a heterogeneous population of target and non-target cells, it binds selectively to the receptors on the surface of the target cells. Exposing the compound to light of selected wave length cleaves it, yielding the active substance.
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Cysteic acid and homocysteic acid analogues of methotrexate and aminopterin (Wed, 26 Dec 1984)
<p>Cysteic acid and homocysteic acid analogues of methotrexate and aminopterin having antitumor activity and low toxicity are soluble in water at a physiological pH ranging from 7.2-7.5. -GOVT PAR The invention described herein was made in the course of work under a grant or award from the Department of Health and Human Services and the U.S. government has certain rights in the invention.</p>
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