3DBS

Structure of PI3K gamma in complex with GDC0941

Summary for 3DBS

• Entry DOI: 10.2210/pdb3dbs/pdb
• Descriptor: Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma isoform, 2-(1H-indazol-4-yl)-6-{[4-(methylsulfonyl)piperazin-1-yl]methyl}-4-morpholin-4-yl-thieno[3,2-d]pyrimidine (2 entities in total)
• Functional Keywords: pi3k gamma, inhibitor, kinase, transferase
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 110411.84

Authors

Wiesmann, C.,Ultsch, M. (deposition date: 2008-06-02, release date: 2008-06-17, Last modification date: 2023-11-01)

Primary citation

Folkes, A.J.,Ahmadi, K.,Alderton, W.K.,Alix, S.,Baker, S.J.,Box, G.,Chuckowree, I.S.,Clarke, P.A.,Depledge, P.,Eccles, S.A.,Friedman, L.S.,Hayes, A.,Hancox, T.C.,Kugendradas, A.,Lensun, L.,Moore, P.,Olivero, A.G.,Pang, J.,Patel, S.,Pergl-Wilson, G.H.,Raynaud, F.I.,Robson, A.,Saghir, N.,Salphati, L.,Sohal, S.,Ultsch, M.H.,Valenti, M.,Wallweber, H.J.A.,Wan, N.C.,Wiesmann, C.,Workman, P.,Zhyvoloup, A.,Zvelebil, M.J.,Shuttleworth, S.J.
The identification of 2-(1H-indazol-4-yl)-6-(4-methanesulfonyl-piperazin-1-ylmethyl)-4-morpholin-4-yl-thieno[3,2-d]pyrimidine (GDC-0941) as a potent, selective, orally bioavailable inhibitor of class I PI3 kinase for the treatment of cancer
J.Med.Chem., 51:5522-5532, 2008

PubMed Abstract: Phosphatidylinositol-3-kinase (PI3K) is an important target in cancer due to the deregulation of the PI3K/ Akt signaling pathway in a wide variety of tumors. A series of thieno[3,2-d]pyrimidine derivatives were prepared and evaluated as inhibitors of PI3 kinase p110alpha. The synthesis, biological activity, and further profiling of these compounds are described. This work resulted in the discovery of 17, GDC-0941, which is a potent, selective, orally bioavailable inhibitor of PI3K and is currently being evaluated in human clinical trials for the treatment of cancer.

PubMed: 18754654
DOI: 10.1021/jm800295d

Experimental method

X-RAY DIFFRACTION (2.8 Å)