3QKL

Spirochromane Akt Inhibitors

3QKL の概要

• エントリーDOI: 10.2210/pdb3qkl/pdb
• 関連するPDBエントリー: 3OCB 3QKK 3QKM
• 分子名称: RAC-alpha serine/threonine-protein kinase, Glycogen synthase kinase-3 beta, N-{(2S)-3-[(3S)-8',9'-dihydro-1H,3'H-spiro[piperidine-3,7'-pyrano[3,2-e]indazol]-1-yl]-2-hydroxypropyl}-N-(2-ethoxyethyl)-2,6-dimethylbenzenesulfonamide, ... (4 entities in total)
• 機能のキーワード: kinase domain, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Cytoplasm: P31749
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 41146.91

構造登録者

Kallan, N.C.,Spencer, K.L.,Blake, J.F.,Xu, R.,Heizer, J.,Bencsik, J.R.,Mitchell, I.S.,Gloor, S.L.,Martinson, M.,Risom, T.,Gross, S.D.,Morales, T.,Vigers, G.P.A.,Brandhuber, B.J.,Skelton, N.J. (登録日: 2011-02-01, 公開日: 2011-03-30, 最終更新日: 2024-11-06)

主引用文献

Kallan, N.C.,Spencer, K.L.,Blake, J.F.,Xu, R.,Heizer, J.,Bencsik, J.R.,Mitchell, I.S.,Gloor, S.L.,Martinson, M.,Risom, T.,Gross, S.D.,Morales, T.H.,Wu, W.I.,Vigers, G.P.,Brandhuber, B.J.,Skelton, N.J.
Discovery and SAR of spirochromane Akt inhibitors.
Bioorg.Med.Chem.Lett., 21:2410-2414, 2011

PubMed Abstract: A novel series of spirochromane pan-Akt inhibitors is reported. SAR optimization furnished compounds with improved enzyme potencies and excellent selectivity over the related AGC kinase PKA. Attempted replacement of the phenol hinge binder provided compounds with excellent Akt enzyme and cell activities but greatly diminished selectivity over PKA.

PubMed: 21392984
DOI: 10.1016/j.bmcl.2011.02.073

実験手法

X-RAY DIFFRACTION (1.9 Å)