Abstract
Coactivator-associated arginine methyltransferase 1 (CARM1) represents a valuable target for hormone-dependent tumors such as prostate and breast cancers. Here we report the enzyme and cellular characterization of the 1-benzyl-3,5-bis(3-bromo-4-hydroxybenzylidene)piperidin-4-one (7g) and its analogues 8a-l. Among them, 7g, 8e, and 8l displayed high and selective CARM1 inhibition, with lower or no activity against a panel of different PRMTs or HKMTs. In human LNCaP cells, 7g showed a significant dose-dependent reduction of the PSA promoter activity.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Cell Line, Tumor
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Cell Survival / drug effects
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Epigenesis, Genetic
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HEK293 Cells
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Humans
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Luciferases / genetics
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Luciferases / metabolism
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Methylation
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Piperidines / chemical synthesis*
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Piperidines / chemistry
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Piperidines / pharmacology
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Poly(A)-Binding Protein I / genetics
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Poly(A)-Binding Protein I / metabolism
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Promoter Regions, Genetic
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Prostate-Specific Antigen / genetics
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Protein-Arginine N-Methyltransferases / antagonists & inhibitors*
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Protein-Arginine N-Methyltransferases / genetics
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Structure-Activity Relationship
Substances
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Piperidines
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Poly(A)-Binding Protein I
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Luciferases
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Protein-Arginine N-Methyltransferases
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coactivator-associated arginine methyltransferase 1
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Prostate-Specific Antigen