2. Academic Validation
  3. Novel 3,5-bis(bromohydroxybenzylidene)piperidin-4-ones as coactivator-associated arginine methyltransferase 1 inhibitors: enzyme selectivity and cellular activity

Novel 3,5-bis(bromohydroxybenzylidene)piperidin-4-ones as coactivator-associated arginine methyltransferase 1 inhibitors: enzyme selectivity and cellular activity

  • J Med Chem. 2011 Jul 14;54(13):4928-32. doi: 10.1021/jm200453n.
Donghang Cheng 1,  Sergio Valente,  Sabrina Castellano,  Gianluca Sbardella,  Roberto Di Santo,  Roberta Costi,  Mark T Bedford,  Antonello Mai
Affiliations

Affiliation

  • 1 The University of Texas MD Anderson Cancer Center, Science Park-Research Division, Smithville, Texas 78957, United States. [email protected]
PMID: 21612300 DOI: 10.1021/jm200453n
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.

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