3NZS

Structure-based Optimization of Pyrazolo -Pyrimidine and -Pyridine Inhibitors of PI3-Kinase

3NZS の概要

• エントリーDOI: 10.2210/pdb3nzs/pdb
• 関連するPDBエントリー: 3NZU
• 分子名称: Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma isoform, 6-(1,1-dioxidothiomorpholin-4-yl)-N-(3-methoxyphenyl)-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-4-amine (2 entities in total)
• 機能のキーワード: kinase p110, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• 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: 109770.06

構造登録者

Murray, J.M.,Wiesmann, C. (登録日: 2010-07-16, 公開日: 2010-12-29, 最終更新日: 2024-02-21)

主引用文献

Staben, S.T.,Heffron, T.P.,Sutherlin, D.P.,Bhat, S.R.,Castanedo, G.M.,Chuckowree, I.S.,Dotson, J.,Folkes, A.J.,Friedman, L.S.,Lee, L.,Lesnick, J.,Lewis, C.,Murray, J.M.,Nonomiya, J.,Olivero, A.G.,Plise, E.,Pang, J.,Prior, W.W.,Salphati, L.,Rouge, L.,Sampath, D.,Tsui, V.,Wan, N.C.,Wang, S.,Wiesmann, C.,Wu, P.,Zhu, B.Y.
Structure-based optimization of pyrazolo-pyrimidine and -pyridine inhibitors of PI3-kinase.
Bioorg.Med.Chem.Lett., 20:6048-6051, 2010

PubMed Abstract: Starting from HTS hit 1a, X-ray co-crystallization and molecular modeling were used to design potent and selective inhibitors of PI3-kinase. Bioavailablity in this series was improved through careful modulation of physicochemical properties. Compound 12 displayed in vivo knockdown of PI3K pharmacodynamic markers such as pAKT, pPRAS40, and pS6RP in a PC3 prostate cancer xenograft model.

PubMed: 20822905
DOI: 10.1016/j.bmcl.2010.08.067

実験手法

X-RAY DIFFRACTION (2.75 Å)