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.
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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Apoptosis*
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Benzamides / chemical synthesis*
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Benzamides / 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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Gossypol / analogs & derivatives*
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Gossypol / chemical synthesis*
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Gossypol / pharmacology
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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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Stereoisomerism
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Structure-Activity Relationship
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Sulfones / chemical synthesis*
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Sulfones / pharmacology
Substances
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Benzamides
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Proto-Oncogene Proteins c-bcl-2
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Sulfones
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TW-37 compound
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Gossypol