title: Novel synthetic pharmacophores inducing a stabilization of cellular microtubules.
abstract: Microtubule drugs have been widely used in cancer chemotherapies. Although microtubules are subject to regulation by signal transduction mechanisms, their pharmacological modulation has so far relied on compounds that bind to the tubulin subunit. Using a cell-based assay designed to probe the microtubule polymerization status, we identified two pharmacophores, CM09 and CM10, as cell-permeable microtubule stabilizing agents. These synthetic compounds do not affect the assembly state of purified microtubules in vitro but they profoundly suppress microtubule dynamics in vivo. Moreover, they exert cytotoxic effects on several cancer cell lines including multidrug resistant cell lines. Therefore, these classes of compounds represent novel attractive leads for cancer chemotherapy.
authors.forename: Anne
authors.initials: A
authors.lastname: Martinez
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Soleilhac
authors.forename: Caroline
authors.initials: C
authors.lastname: Barette
authors.forename: Renaud
authors.initials: R
authors.lastname: Prudent
authors.forename: Gustavo J
authors.initials: GJ
authors.lastname: Gozzi
authors.forename: Emilie
authors.initials: E
authors.lastname: Vassal-Stermann
authors.forename: Catherine
authors.initials: C
authors.lastname: Pillet
authors.forename: Attilio
authors.initials: A
authors.lastname: Di Pietro
authors.forename: Marie-Odile
authors.initials: MO
authors.lastname: Fauvarque
authors.affiliation: Centre de Recherche INSERM-UJF U823, Institut Albert Bonniot, Team 3 "Polarity, Development and Cancer", UJF Site Sante, BP 170-La Tronche-38042 Grenoble Cedex 9 - France. laurence.lafanechere@ujf-grenoble.fr.
authors.forename: Laurence
authors.initials: L
authors.lastname: Lafanechere
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D018929:Cell Culture Techniques; D002453:Cell Cycle / Q000187:drug effects*; D002470:Cell Survival; D015195:Drug Design; D005455:Fluorescent Antibody Technique; D006367:HeLa Cells / Q000187:drug effects*; D006801:Humans; D008870:Microtubules / Q000187:drug effects* / Q000502:physiology; D014404:Tubulin / Q000187:drug effects*; D050257:Tubulin Modulators / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D014404:Tubulin; D050257:Tubulin Modulators