Targeting PI3-Kinase Pathway: Patents Summary 2010 and 2011

Phosphatidylinositol-3-kinases, PI3Ks, constitute a lipid kinase family characterized by their ability to phosphorylate inositol ring 3´-OH group in inositol phospholipids generating the second messenger phosphatidylinositol-3,4,5-tris-phosphate (PIP3).


PI3K family is involved in a diverse set of cellular functions, including cell growth, proliferation, motility, differentiation, glucose transport, survival intracellular trafficking and membrane ruffling.


Activation of the PI3K pathway is a recurrent feature observed in human tumors, and the role of this pathway for the maintenance of the tumorigenic state has been clearly underlined.

PI3Ks can be categorized in three major class designed as class I, class II, or class III, depending on their subunit structure, regulation and substrate selectivity.


Class I:

Substrates for class I PI3Ks are phosphatidylinositol (PI), PI-4-phosphate (PI4P) and PI-4,5-biphosphate (PI(4,5)P2). Class I is divided into two groups (Ia and Ib) because of their activation mechanism and associated regulatory subunit. Class Ia PI3Ks includes PI3K p110a, p110b and p110d subtypes, and is typically activated by tyrosine kinase-coupled receptors. The class Ib is activated by a G-protein-coupled receptor via the subunit p110g.

Class II:

Contains PI3K C2a, b and g isoforms (characterized by the presence of C2 domains at C terminus). PI and PI4P are the known substrates.

Class III:

The substrate for this class is only the PI.

Scheme 1.PI3K Class Ia signaling pathway.

Activation of growth factor receptor tyrosine kinases results in phosphorylation on tyrosine residues of the receptor and leads to the recruitment of PI3Ks to the membrane (with or without adaptors). PI3Ks primarily phosphorylate phosphatidylinositol-4,5-bisphosphate (PIP2) on the plasma membrane to generate the second messenger, phosphatidylinositol-3,4,5-trisphosphate (PIP3). Accumulation of PIP3 on the cell membrane leads to the colocalization of signalling proteins, including Akt and PDK1.

Once activated, by phosphorylating several cellular proteins, Akt mediates the activation and the inhibition of several targets, resulting in cellular survival, growth and proliferation through various mechanisms.

The 3-phosphatase PTEN dephosphorylates PIP3 and negatively regulates the PI3/Akt pathway.

Some inhibitors structures

Table 1. Current PI3K inhibitors in 2010 and 2011’s patents*

Company Target(s) Patent number
AMGEN INC. PI3K and/or mTOR WO2010126895
AMGEN INC. PI3K WO2010108074
AMGEN INC. PI3K and/or mTOR WO2010132598
CENTRO NACIONAL DE INVESTIGACIONES ONCOLOGICAS (CNIO) PI3K (class I particularly) WO2010112874
CENTRO NACIONAL DE INVESTIGACIONES ONCOLOGICAS (CNIO) PI3K and/or mTOR WO2010119264
CENTRO NACIONAL DE INVESTIGACIONES ONCOLOGICAS (CNIO)   PI3K-Akt WO2010079423 
EXELIXIS INC.   PI3Kalpha and mTOR WO2010039740 
GLAXO GROUP LIMITED   PI3K WO2010102958 
GLAXO GROUP LIMITED   PI3K WO2010125082 
GLAXOSMITHKLINE LLC   PI3K-beta WO2010135504 
INTELLIKINE INC.   PI3K and/or mTOR WO2010006086 
INTELLIKINE INC.   PI3K and/or mTOR WO2010051042 
INTELLIKINE INC.   PI3K and/or mTOR WO2010051043 
INTELLIKINE INC. PI3K and/or mTOR WO2010129816
MERCK SERONO S.A. PI3K WO2010100144
TYROGENEX INC. PI3K and/or mTOR WO2010056320
UCB PHARMA PI3Kalpha and/or PI3Kbeta and/or PI3Kgamma and/or PI3Kdelta WO2010001126
UCB PHARMA PI3K WO2010052448
UCB PHARMA PI3K WO2010061180
UCB PHARMA PI3K WO2010092340
UCB PHARMA PI3K WO2010100405
UCB PHARMA PI3K WO2010133836
WYETH PI3K and/or mTOR WO2010002954
WYETH PI3K and/or mTOR WO2010011620
WYETH PI3K and/or mTOR WO2010030727
WYETH PI3K and/or mTOR WO2010030967
WYETH PI3K and/or mTOR WO2010120987
WYETH mTOR, PI3K and HSMG-1 WO2010120991
WYETH PI3K and/or mTOR WO2010120994
WYETH PI3K and/or mTOR WO2010120996
WYETH PI3K and/or mTOR WO2010120998
XCOVERY INC. PI3K WO2010005558
AVILA THERAPEUTICS, INC. PI3K WO2011031896
CENTRO NACIONAL DE INVESTIGACIONES ONCOLOGIGAS (CNIO) PI3K WO2011036461
F. HOFFMANN-LA ROCHE AG PI3K WO2011036280
GLAXOSMITHKLINE LLC PI3K and MEK WO2011038380
GLAXOSMITHKLINE LLC PI3K and MEK WO2011046894
INTELLIKINE, INC. PI3K WO2011008302
INTELLIKINE, INC. PI3K WO2011022439
PRESIDENT AND FELLOWS OF HARVARD COLLEGE / SHANGAI INSTITUTE OF ORGANIC CHEMISTRY INC. PI3K WO2011011522
TAISHO PHARMACEUTICAL CO., LTD. PI3K WO2011048936

*Source WIPO

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