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
  • 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.