Structure-Based Design of Potent Small-Molecule Inhibitors of Anti-Apoptotic Bcl-2 Proteins
Journal of Medicinal Chemistry2006Vol. 49(21), pp. 6139–6142
Citations Over TimeTop 10% of 2006 papers
Guoping Wang, Zaneta Nikolovska‐Coleska, Chao‐Yie Yang, Renxiao Wang, Guozhi Tang, Jie Guo, Sanjeev Shangary, Su Qiu, Wei Gao, Dajun Yang, Jennifer L. Meagher, Jeanne A. Stuckey, Krzysztof Krajewski, Sheng Jiang, Peter P. Roller, Hatice Özel Abaan, York Tomita, Shaomeng Wang
Abstract
A structure-based approach was employed to design a new class of small-molecule inhibitors of Bcl-2. The most potent compound 5 (TW-37) binds to Bcl-2 with a K(i) value of 290 nM and also to Bcl-xL and Mcl-1 with high affinities. Compound 5 potently inhibits cell growth in PC-3 prostate cancer cells with an IC(50) value of 200 nM and effectively induces apoptosis in a dose-dependent manner.
Related Papers
- → Structure activity relationship and optimization of N-(3-(2-aminothiazol-4-yl)aryl)benzenesulfonamides as anti-cancer compounds against sensitive and resistant cells(2017)15 cited
- → Peptidic HIV integrase inhibitors derived from HIV gene products: Structure–activity relationship studies(2010)22 cited
- → Discovery of benzhydrylpiperazine derivatives as CB1 receptor inverse agonists via privileged structure-based approach(2009)20 cited
- → Synthesis and SAR studies of a novel class of S1P1 receptor antagonists(2007)14 cited
- → Design, synthesis and SAR analysis of novel potent and selective small molecule antagonists of NPBWR1 (GPR7)(2012)8 cited