N-（2-氨基苯基）-4- [（4-吡啶-3-基嘧啶-2-基氨基）甲基]苯甲酰胺（MGCD0103）的发现，一种口服活性组蛋白脱乙酰酶抑制剂。
Discovery of N-(2-aminophenyl)-4-[(4-pyridin-3-ylpyrimidin-2-ylamino)methyl]benzamide (MGCD0103), an orally active histone deacetylase inhibitor.
作者信息
Zhou Nancy, Moradei Oscar, Raeppel Stephane, Leit Silvana, Frechette Sylvie, Gaudette Frederic, Paquin Isabelle, Bernstein Naomy, Bouchain Giliane, Vaisburg Arkadii, Jin Zhiyun, Gillespie Jeff, Wang James, Fournel Marielle, Yan Pu T, Trachy-Bourget Marie-Claude, Kalita Ann, Lu Aihua, Rahil Jubrail, MacLeod A Robert, Li Zuomei, Besterman Jeffrey M, Delorme Daniel
机构信息
MethylGene Inc., 7220 Frederick-Banting, Montréal, Québec H4S 2A1, Canada.
出版信息
J Med Chem. 2008 Jul 24;51(14):4072-5. doi: 10.1021/jm800251w. Epub 2008 Jun 21.
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.
描述了N-(2-氨基苯基)-4-[(4-吡啶-3-基嘧啶-2-基氨基)甲基]苯甲酰胺8（MGCD0103）的设计、合成及生物学评价。化合物8是一种亚型选择性小分子组蛋白去乙酰化酶（HDAC）抑制剂，在体外亚微摩尔浓度下可选择性抑制HDACs 1-3和11。8可阻断癌细胞增殖并诱导组蛋白乙酰化、p21（cip/waf1）蛋白表达、细胞周期阻滞及凋亡。8具有口服生物利用度，在体内具有显著的抗肿瘤活性，已进入临床试验，有望成为一种抗癌药物。
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