COBRA-1, a rationally-designed epoxy-THF containing compound with potent tubulin depolymerizing activity as a novel anticancer agent

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 can...

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Bibliographic Details
Published in:Bioorganic & medicinal chemistry letters 2000-06, Vol.10 (11), p.1193-1197
Main Authors: JAN, S.-T, CHEN MAO, VASSILEV, A. O, NAVARA, C. S, UCKUN, F. M
Format: Article
Language:English
Subjects:
Antineoplastic agents
Antineoplastic Agents - chemistry
Antineoplastic Agents - pharmacology
Biological and medical sciences
Drug Design
Furans - chemistry
Furans - pharmacology
General aspects
Humans
Medical sciences
Models, Molecular
Pharmacology. Drug treatments
Tubulin - drug effects
Tubulin - metabolism
Tumor Cells, Cultured
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Summary: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.
ISSN:0960-894X
1464-3405
DOI:10.1016/S0960-894X(00)00212-2