2GU8

Discovery of 2-Pyrimidyl-5-Amidothiophenes as Novel and Potent Inhibitors for AKT: Synthesis and SAR Studies

2GU8 の概要

• エントリーDOI: 10.2210/pdb2gu8/pdb
• 分子名称: CAMP-dependent protein kinase, alpha-catalytic subunit, inhibitor of CAMP-dependent protein kinase, N-[(1S)-2-AMINO-1-(2,4-DICHLOROBENZYL)ETHYL]-5-[2-(METHYLAMINO)PYRIMIDIN-4-YL]THIOPHENE-2-CARBOXAMIDE, ... (4 entities in total)
• 機能のキーワード: camp-dependent protein kinase, pka, akt, kinase, drug design, ternary complex, signaling protein, transferase-inhibitor complex, transferase/inhibitor
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm (By similarity): P17612
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 42076.76

構造登録者

Murray, J.M. (登録日: 2006-04-28, 公開日: 2007-05-01, 最終更新日: 2024-10-16)

主引用文献

Lin, X.,Murray, J.M.,Rico, A.C.,Wang, M.X.,Chu, D.T.,Zhou, Y.,Del Rosario, M.,Kaufman, S.,Ma, S.,Fang, E.,Crawford, K.,Jefferson, A.B.
Discovery of 2-pyrimidyl-5-amidothiophenes as potent inhibitors for AKT: synthesis and SAR studies
Bioorg.Med.Chem.Lett., 16:4163-4168, 2006

PubMed Abstract: A series of 2-pyrimidyl-5-amidothiophenes has been synthesized and evaluated for AKT inhibition. SAR studies resulted in potent inhibitors of AKT with IC(50) values as low as single digit nanomolar as represented by compound 2aa. Compound 2aa showed cellular activity including antiproliferation and downstream target modulation. Selectivity profile is described. A co-crystal of 2aa with PKA is determined and discussed.

PubMed: 16765046
DOI: 10.1016/j.bmcl.2006.05.092

実験手法

X-RAY DIFFRACTION (2.2 Å)