Pyrogallol-based molecules as potent inhibitors of the antiapoptotic Bcl-2 proteins.
We report herein a new class of small-molecule inhibitors of antiapoptotic Bcl-2 proteins. The most potent compound, 7, binds to Bcl-2, Bcl-xL, and Mcl-1 proteins with Ki of 110, 638, and 150 nM, respectively. Compound 7 is highly effective in induction of cell death in breast cancer cells with high levels of Bcl-2, Bcl-xL, and Mcl-1 proteins and represents a promising lead compound for the design of new anticancer drugs.
Tang
Guozhi
G
Department of Internal Medicine, Comprehensive Cancer Center, and Life Sciences Institute, University of Michigan, 1500 East Medical Center Drive, Ann Arbor, Michigan 48109, USA.
Yang
Chao-Yie
CY
Nikolovska-Coleska
Zaneta
Z
Guo
Jie
J
Qiu
Su
S
Wang
Renxiao
R
Gao
Wei
W
Wang
Guoping
G
Stuckey
Jeanne
J
Krajewski
Krzysztof
K
Jiang
Sheng
S
Roller
Peter P
PP
Wang
Shaomeng
S
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D017209:Apoptosis; D001667:Binding, Competitive; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008958:Models, Molecular; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000037:antagonists & inhibitors*; D011748:Pyrogallol / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology; D011869:Radioligand Assay; D013329:Structure-Activity Relationship; D051020:bcl-X Protein / Q000037:antagonists & inhibitors
D000970:Antineoplastic Agents; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D009363:Neoplasm Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051020:bcl-X Protein; D011748:Pyrogallol