title: Structure-based design of potent small-molecule inhibitors of anti-apoptotic Bcl-2 proteins.
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.
authors.affiliation: Comprehensive Cancer Center and Department of Internal Medicine, University of Michigan, 1500 E. Medical Center Drive, Ann Arbor, Michigan 48109, USA.
authors.forename: Guoping
authors.initials: G
authors.lastname: Wang
authors.forename: Zaneta
authors.initials: Z
authors.lastname: Nikolovska-Coleska
authors.forename: Chao-Yie
authors.initials: CY
authors.lastname: Yang
authors.forename: Renxiao
authors.initials: R
authors.lastname: Wang
authors.forename: Guozhi
authors.initials: G
authors.lastname: Tang
authors.forename: Jie
authors.initials: J
authors.lastname: Guo
authors.forename: Sanjeev
authors.initials: S
authors.lastname: Shangary
authors.forename: Su
authors.initials: S
authors.lastname: Qiu
authors.forename: Wei
authors.initials: W
authors.lastname: Gao
authors.forename: Dajun
authors.initials: D
authors.lastname: Yang
authors.forename: Jennifer
authors.initials: J
authors.lastname: Meagher
authors.forename: Jeanne
authors.initials: J
authors.lastname: Stuckey
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Krajewski
authors.forename: Sheng
authors.initials: S
authors.lastname: Jiang
authors.forename: Peter P
authors.initials: PP
authors.lastname: Roller
authors.forename: Hatice Ozel
authors.initials: HO
authors.lastname: Abaan
authors.forename: York
authors.initials: Y
authors.lastname: Tomita
authors.forename: Shaomeng
authors.initials: S
authors.lastname: Wang
mesh_terms: D017209:Apoptosis; D001549:Benzamides / Q000138:chemical synthesis* / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D006072:Gossypol / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology; D006801:Humans; D008958:Models, Molecular; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000037:antagonists & inhibitors*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013450:Sulfones / Q000138:chemical synthesis* / Q000494:pharmacology
chemical_list: D001549:Benzamides; D019253:Proto-Oncogene Proteins c-bcl-2; D013450:Sulfones; C515128:TW-37 compound; D006072:Gossypol