Potent Farnesyltransferase Inhibitors with 1,4-Diazepane Scaffolds as Novel Destabilizing Microtubule Agents in Hormone-Resistant Prostate Cancer
journal contributionposted on 10.03.2011, 00:00 by Nicolas Wlodarczyk, Delphine Le Broc-Ryckewaert, Pauline Gilleron, Amélie Lemoine, Amaury Farce, Philippe Chavatte, Joëlle Dubois, Nicole Pommery, Jean-Pierre Hénichart, Christophe Furman, Régis Millet
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.