Discovery of N-(2-Aminophenyl)-4-[(4-pyridin-3-ylpyrimidin-2-ylamino)methyl]benzamide (MGCD0103), an Orally Active Histone Deacetylase Inhibitor
Journal of Medicinal Chemistry2008Vol. 51(14), pp. 4072–4075
Citations Over TimeTop 10% of 2008 papers
Nancy Zhou, Oscar Moradei, Stéphane Raeppel, Silvana Leit, Sylvie Fréchette, Frédéric Gaudette, Isabelle Paquin, Naomy Bernstein, Giliane Bouchain, Arkadii Vaisburg, Zhiyun Jin, J. H. Gillespie, Jinru Wang, Marielle Fournel, Pu Yan, Marie-Claude Trachy-Bourget, Ann Kalita, Aihua Lu, Jubrail Rahil, A. Robert MacLeod, Zuomei Li, Jeffrey M. Besterman, Daniel Delorme
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.
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