PELORUSIDE A

Source: The New Zealand sponge Mycale hentscheli (PORIFERA)
Activity: tubulin interactive agent
Status: Preclinical

University of Victoria scientist Peter Northcote and colleagues recovered the compound Peloruside A from the sponge Mycale hentscheli collected from Pelorus Sound, New Zealand. Not much has been published on this tubulin interactive compound since the initial report in 2000. But, this relatively simple compound may facilitate exploration of synthetic and semi-synthetic derivatives if the basic bioactivity looks promising.

Dr Northcote reports that Peloruside A shares a molecular target with the popular commercial cancer therapy agent paclitaxel. Peloruside A appears to bind tubulin and arrests target cell development at the G2-M transition stage of the cell cycle, triggering apoptosis ('cell suicide') before mitosis (M Phase) can begin.

Very recently, the compound was licensed from the University of Texas Southwestern Medical Center at Dallas and Victoria University of Wellington, New Zealand, by biopharmaceutical company Reata Pharmaceuticals, Inc.. Scientists from this company recently completed the first total synthesis of peloruside A, and they suggest the compound has a chemical scaffold that is amenable to modification for the purpose of drug development. They believe Peloruside A could enter clinical trials as early as 2007.

Efforts are also ongoing by researchers from New Zealand's National Institute of Water and Atmospheric Research (NIWA) to successfully culture the sponge while retaining bioactivity similar to that found in wild stocks.

NCBI PubMed biomedical literature citations and abstracts - [ LINK ]

References

Hood KA, West LM, Rouwe B, Northcote PT, Berridge MV, Wakefield SJ, and JH Miller. 2002. Peloruside A, a novel antimitotic agent with paclitaxel-like microtubule- stabilizing activity. Cancer Res. 15;62:3356-60.

Newman DJ, and GM Cragg. 2004. Advanced Preclinical and Clinical trials of natural Products and Related Compounds from marine Sources. Current Medicinal Chemistry 11:1693-1713.

West LM, Northcote PT, and CN Battershill. 2000. Peloruside A: A potent cytotoxic macrolide isolated from the New Zealand Marine Sponge Mycale sp. J. Org. Chem 65:445-449.

Reata Announces Licensing of Novel Natural Products with Anticancer Potential (05/10/05):
http://www.reatapharma.com/news_details.asp?IDnews=11

Potential anticancer discovery heads to development (05/11/05):
http://www.vic-link.co.nz/media/potential-anti-cancer.htm