Abstract
A series of acylpyrogallols were designed, synthesized, and evaluated as small-molecule inhibitors of antiapoptotic Bcl-2 proteins. The most potent compound 9 (TM-179) binds to Bcl-2 with an IC50 of 170 nM and to Mcl-1 with a Ki of 37 nM. Compound 9 potently inhibits cell growth and induces apoptosis in human breast and prostate cancer cell lines.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Antineoplastic Agents / chemical synthesis*
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Antineoplastic Agents / pharmacology
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Apoptosis*
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Benzothiazoles / chemical synthesis*
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Benzothiazoles / pharmacology
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Cell Line, Tumor
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Cell Proliferation / drug effects
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Drug Screening Assays, Antitumor
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Humans
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Models, Molecular
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Proto-Oncogene Proteins c-bcl-2 / antagonists & inhibitors*
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Pyrogallol / analogs & derivatives*
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Pyrogallol / chemical synthesis*
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Pyrogallol / pharmacology
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Structure-Activity Relationship
Substances
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Antineoplastic Agents
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Benzothiazoles
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Proto-Oncogene Proteins c-bcl-2
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TM 179
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Pyrogallol