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Discovery of novel Myc-Max heterodimer disruptors with a three-dimensional pharmacophore model.

ABSTRACT: 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.

SUBMITTER: Mustata G

PROVIDER: S-EPMC2765518 | biostudies-literature | 2009 Mar

REPOSITORIES: biostudies-literature

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Discovery of novel Myc-Max heterodimer disruptors with a three-dimensional pharmacophore model.

Mustata Gabriela G Follis Ariele Viacava AV Hammoudeh Dalia I DI Metallo Steven J SJ Wang Huabo H Prochownik Edward V EV Lazo John S JS Bahar Ivet I

Journal of medicinal chemistry 20090301 5

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 ...[more]

PMID: 19215087

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