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[Cancer Research 62, 3356-3360, June 15, 2002]
© 2002 American Association for Cancer Research

Advances in Brief

Peloruside A, a Novel Antimitotic Agent with Paclitaxel-like Microtubule- stabilizing Activity1

Kylie A. Hood, Lyndon M. West2, Berber Rouwé3, Peter T. Northcote, Michael V. Berridge, St. John Wakefield and John H. Miller4

Schools of Biological Sciences [K. A. H., B. R., J. H. M.] and Chemical and Physical Sciences [L. M. W., P. T. N.], Victoria University of Wellington, Wellington, New Zealand; Malaghan Institute of Medical Research, Wellington South, New Zealand [M. V. B.]; and Department of Pathology, Wellington School of Medicine, Wellington, New Zealand [S. J. W.]

Peloruside A is a novel secondary metabolite isolated from a New Zealand marine sponge, Mycale hentscheli, that has potent paclitaxel-like microtubule-stabilizing activity and is cytotoxic at nanomolar concentrations. Its 16-membered macrolide ring is similar to that of epothilone, a drug currently under clinical investigation as an anticancer agent. Like paclitaxel, peloruside A arrests cells in the G2-M phase of the cell cycle and induces apoptosis. The relatively simple structure of peloruside makes it suitable for the design and synthesis of analogues with improved tumor targeting and reduced tumor cross-resistance.




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