Discovery of Novel Myc-Max Heterodimer Disruptors with a Three-Dimensional Pharmacophore Model

被引：70

作者：

Mustata, Gabriela ^{[1
]}

Follis, Ariele Viacava ^{[3
]}

Hammoudeh, Dalia I. ^{[3
]}

Metallo, Steven J. ^{[3
]}

Wang, Huabo ^{[4
,5
]}

Prochownik, Edward V. ^{[4
,5
]}

Lazo, John S. ^{[2
]}

Bahar, Ivet ^{[1
]}

机构：

[1] Univ Pittsburgh, Dept Computat Biol, Pittsburgh, PA 15260 USA

[2] Univ Pittsburgh, Dept Pharmacol & Chem Biol, Pittsburgh, PA 15260 USA

[3] Georgetown Univ, Dept Chem, Washington, DC 20057 USA

[4] Univ Pittsburgh, Med Ctr, Childrens Hosp Pittsburgh, Hematol Oncol Sect, Pittsburgh, PA 15201 USA

[5] Univ Pittsburgh, Med Ctr, Dept Microbiol & Mol Genet, Pittsburgh, PA 15201 USA

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2009年 / 52卷 / 05期

关键词：

C-MYC; MYC/MAX DIMERIZATION; INHIBITION; GALAHAD;

D O I：

10.1021/jm801278g

中图分类号：

R914 [药物化学];

学科分类号：

100705 [微生物与生化药学];

摘要：

A three-dimensional pharmacophore model was generated utilizing a set of known inhibitors of c-Myc-Max heterodimer formation. The model successfully identified a set of structurally diverse compounds with potential inhibitory activity against c-Myc. Nine compounds were tested in vitro. and four displayed affinities in the micromolar range and growth inhibitory activity against c-Myc-overexpressing cells. These studies demonstrate the applicability of pharmacophore modeling to the identification of novel and potentially more puissant inhibitors of the c-Myc oncoprotein.

引用

页码：1247 / 1250

页数：4

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