3DBS

Structure of PI3K gamma in complex with GDC0941

3DBS の概要

• エントリーDOI: 10.2210/pdb3dbs/pdb
• 分子名称: 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)
• 機能のキーワード: pi3k gamma, inhibitor, kinase, transferase
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 110411.84

構造登録者

Wiesmann, C.,Ultsch, M. (登録日: 2008-06-02, 公開日: 2008-06-17, 最終更新日: 2023-11-01)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2.8 Å)