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

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

  • J Med Chem. 2008 Jul 24;51(14):4072-5. doi: 10.1021/jm800251w.
Nancy Zhou 1,  Oscar Moradei,  Stephane Raeppel,  Silvana Leit,  Sylvie Frechette,  Frederic Gaudette,  Isabelle Paquin,  Naomy Bernstein,  Giliane Bouchain,  Arkadii Vaisburg,  Zhiyun Jin,  Jeff Gillespie,  James Wang,  Marielle Fournel,  Pu T Yan,  Marie-Claude Trachy-Bourget,  Ann Kalita,  Aihua Lu,  Jubrail Rahil,  A Robert MacLeod,  Zuomei Li,  Jeffrey M Besterman,  Daniel Delorme
Affiliations

Affiliation

  • 1 MethylGene Inc., 7220 Frederick-Banting, Montréal, Québec H4S 2A1, Canada.
PMID: 18570366 DOI: 10.1021/jm800251w
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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