Potent farnesyltransferase inhibitors with 1,4-diazepane scaffolds as novel destabilizing microtubule agents in hormone-resistant prostate cancer

J Med Chem. 2011 Mar 10;54(5):1178-90. doi: 10.1021/jm101067y.

Nicolas Wlodarczyk ¹, Delphine Le Broc-Ryckewaert, Pauline Gilleron, Amélie Lemoine, Amaury Farce, Philippe Chavatte, Joëlle Dubois, Nicole Pommery, Jean-Pierre Hénichart, Christophe Furman, Régis Millet

Affiliations

Affiliation

1 Institut de Chimie Pharmaceutique Albert Lespagnol, Université Lille-Nord de France, EA4481, IFR114, 3 Rue du Pr Laguesse, BP 83, F-59006 Lille, France.

PMID: 21299244 DOI: 10.1021/jm101067y

Abstract

A new class of potent farnesyltransferase inhibitors based on a 1,4-diazepane scaffold was synthesized with protein farnesyltransferase inhibition potencies in the low nanomolar range. The compounds block the growth on two hormone-resistant tumor prostatic cell lines (DU145 and PC3). The advanced cellular evaluation of the more potent farnesyltransferase inhibitors was explored and revealed a disorganization of tubulin in PC3 cells.

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