title: COBRA-1, a rationally-designed epoxy-THF containing compound with potent tubulin depolymerizing activity as a novel anticancer agent.
abstract: A novel mono-THF containing synthetic anticancer drug, COBRA-1, was designed for targeting a previously unrecognized unique narrow binding cavity on the surface of alpha-tubulin. COBRA-1 inhibited GTP-induced tubulin polymerization in cell-free tubulin turbidity assays. Treatment of human breast cancer and brain tumor (glioblastoma) cells with COBRA-1 caused destruction of microtubule organization and apoptosis. Like other microtubule-interfering agents, COBRA-1 activated the proapoptotic c-Jun N-terminal kinase (JNK) signal transduction pathway, as evidenced by rapid induction of c-jun expression.
authors.affiliation: Drug Discovery Program and Parker Hughes Cancer Center, Parker Hughes Institute, St. Paul, MN 55113, USA.
authors.forename: S T
authors.initials: ST
authors.lastname: Jan
authors.forename: C
authors.initials: C
authors.lastname: Mao
authors.forename: A O
authors.initials: AO
authors.lastname: Vassilev
authors.forename: C S
authors.initials: CS
authors.lastname: Navara
authors.forename: F M
authors.initials: FM
authors.lastname: Uckun
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D015195:Drug Design; D005663:Furans / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D008958:Models, Molecular; D014404:Tubulin / Q000187:drug effects* / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; C414943:COBRA 1; D005663:Furans; D014404:Tubulin