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J Med Chem. 2008 Jul 24;51(14):4072-5. doi: 10.1021/jm800251w. Epub 2008 Jun 21.

Discovery of N-(2-aminophenyl)-4-[(4-pyridin-3-ylpyrimidin-2-ylamino)methyl]benzamide (MGCD0103), an orally active histone deacetylase inhibitor.

Author information

1
MethylGene Inc., 7220 Frederick-Banting, Montréal, Québec H4S 2A1, Canada.

Abstract

The design, synthesis, and biological evaluation of N-(2-aminophenyl)-4-[(4-pyridin-3-ylpyrimidin-2-ylamino)methyl]benzamide 8 (MGCD0103) is described. Compound 8 is an isotype-selective small molecule histone deacetylase (HDAC) inhibitor that selectively inhibits HDACs 1-3 and 11 at submicromolar concentrations in vitro. 8 blocks cancer cell proliferation and induces histone acetylation, p21 (cip/waf1) protein expression, cell-cycle arrest, and apoptosis. 8 is orally bioavailable, has significant antitumor activity in vivo, has entered clinical trials, and shows promise as an anticancer drug.

PMID:
18570366
DOI:
10.1021/jm800251w
[Indexed for MEDLINE]

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