title: Novel 3,5-bis(bromohydroxybenzylidene)piperidin-4-ones as coactivator-associated arginine methyltransferase 1 inhibitors: enzyme selectivity and cellular activity.
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.
authors: The University of Texas MD Anderson Cancer Center, Science Park-Research Division, Smithville, Texas 78957, United States. dcheng@mdanderson.org
authors: Donghang
authors: D
authors: Cheng
authors: Sergio
authors: S
authors: Valente
authors: Sabrina
authors: S
authors: Castellano
authors: Gianluca
authors: G
authors: Sbardella
authors: Roberto
authors: R
authors: Di Santo
authors: Roberta
authors: R
authors: Costi
authors: Mark T
authors: MT
authors: Bedford
authors: Antonello
authors: A
authors: Mai
references: ChemMedChem. 2007 Jul;2(7):987-91
references: 17458842
references: Bioorg Med Chem Lett. 2009 Feb 15;19(4):1218-23
references: 19131248
references: J Biol Chem. 2010 Mar 5;285(10):7143-52
references: 20022955
references: Prostate. 2006 Sep 1;66(12):1292-301
references: 16705743
references: Mol Cell. 2005 Apr 29;18(3):263-72
references: 15866169
references: EMBO Rep. 2002 Mar;3(3):268-73
references: 11850402
references: Bioorg Med Chem Lett. 2008 Aug 1;18(15):4438-41
references: 18619839
references: J Med Chem. 2010 Feb 11;53(3):1407-11
references: 20041717
references: J Biol Chem. 2010 Jan 8;285(2):1147-52
references: 19897492
references: Biochim Biophys Acta. 2009 Jan;1789(1):45-57
references: 18603028
references: J Med Chem. 2006 Nov 16;49(23):6897-907
references: 17154519
references: J Biol Chem. 2007 Jun 8;282(23):16917-23
references: 17439947
references: Cancer. 2004 Jul 1;101(1):83-9
references: 15221992
references: Bioorg Med Chem Lett. 2009 Dec 1;19(23):6725-32
references: 19836951
references: Cancer Res. 2008 Jan 1;68(1):301-6
references: 18172323
references: Science. 1999 Jun 25;284(5423):2174-7
references: 10381882
references: Mol Cell. 2007 Jan 12;25(1):71-83
references: 17218272
references: J Med Chem. 2008 Apr 10;51(7):2279-90
references: 18348515
references: Mol Cell Biol. 1995 Apr;15(4):1907-14
references: 7891684
references: Proc Natl Acad Sci U S A. 2006 Sep 5;103(36):13351-6
references: 16938873
references: J Am Chem Soc. 2010 May 19;132(19):6827-33
references: 20415477
references: Mol Cell. 2009 Jan 16;33(1):1-13
references: 19150423
references: J Biol Chem. 2005 Sep 2;280(35):30888-98
references: 15998636
references: Brain Res. 2007 Jun 25;1155:1-9
references: 17512914
references: J Med Chem. 2006 Oct 5;49(20):6046-56
references: 17004718
references: Bioorg Med Chem Lett. 2009 Sep 1;19(17):5063-6
references: 19632837
references: J Med Chem. 2007 Apr 19;50(8):1973-7
references: 17348637
references: Bioorg Med Chem Lett. 2009 Jun 1;19(11):2924-7
references: 19419866