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

S T Jan; C Mao; A O Vassilev; C S Navara; F M Uckun

doi:10.1016/s0960-894x(00)00212-2

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

S T Jan·C Mao·A O Vassilev·C S Navara·F M Uckun

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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.

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Antineoplastic Agents Drug Design Furans Humans Models, Molecular Tubulin Tumor Cells, Cultured Journal Article

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S T Jan, C Mao, A O Vassilev, C S Navara, F M Uckun. 2000-06-05. COBRA-1, a rationally-designed epoxy-THF containing compound with potent tubulin depolymerizing activity as a novel anticancer agent.. https://doi.org/10.1016/s0960-894x(00)00212-2

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