title: Structure-based design of flavonoid compounds as a new class of small-molecule inhibitors of the anti-apoptotic Bcl-2 proteins.
abstract: Structure-based strategy was employed to design flavonoid compounds to mimic the Bim BH3 peptide as a new class of inhibitors of the anti-apoptotic Bcl-2 proteins. The most potent compound, 4 (BI-33), binds to Bcl-2 and Mcl-1 with Ki values of 17 and 18 nM, respectively. Compound 4 inhibits cell growth in the MDA-MB-231 breast cancer cell line with an IC50 value of 110 nM and effectively induces apoptosis.
authors.affiliation: Comprehensive Cancer Center and Department of Internal Medicine, University of Michigan, 1500 East Medical Center Drive, Ann Arbor, Michigan 48109, USA.
authors.forename: Guozhi
authors.initials: G
authors.lastname: Tang
authors.forename: Ke
authors.initials: K
authors.lastname: Ding
authors.forename: Zaneta
authors.initials: Z
authors.lastname: Nikolovska-Coleska
authors.forename: Chao-Yie
authors.initials: CY
authors.lastname: Yang
authors.forename: Su
authors.initials: S
authors.lastname: Qiu
authors.forename: Sanjeev
authors.initials: S
authors.lastname: Shangary
authors.forename: Renxiao
authors.initials: R
authors.lastname: Wang
authors.forename: Jie
authors.initials: J
authors.lastname: Guo
authors.forename: Wei
authors.initials: W
authors.lastname: Gao
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: Shaomeng
authors.initials: S
authors.lastname: Wang
mesh_terms: D017209:Apoptosis / Q000502:physiology*; D045744:Cell Line, Tumor; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D005419:Flavonoids / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D015394:Molecular Structure; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000037:antagonists & inhibitors* / Q000502:physiology
chemical_list: D005419:Flavonoids; D019253:Proto-Oncogene Proteins c-bcl-2