Structure-based design of flavonoid compounds as a new class of small-molecule inhibitors of the anti-apoptotic Bcl-2 proteins.
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.
Tang
Guozhi
G
Comprehensive Cancer Center and Department of Internal Medicine, University of Michigan, 1500 East Medical Center Drive, Ann Arbor, Michigan 48109, USA.
Ding
Ke
K
Nikolovska-Coleska
Zaneta
Z
Yang
Chao-Yie
CY
Qiu
Su
S
Shangary
Sanjeev
S
Wang
Renxiao
R
Guo
Jie
J
Gao
Wei
W
Meagher
Jennifer
J
Stuckey
Jeanne
J
Krajewski
Krzysztof
K
Jiang
Sheng
S
Roller
Peter P
PP
Wang
Shaomeng
S
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
D005419:Flavonoids; D019253:Proto-Oncogene Proteins c-bcl-2