SPISULOSINE (ES-285)

Molecular Weight: 321 g/mol
Molecular Formula: C₁₈H₄₀ClNO

Source: The bivalve Spisula (=Mactromeris) polynyma (MOLLUSCA)
Activity: Antitumor agent
Status: Currently in Phase I clinical trials

Isolation of this natural product from the commercially harvested Arctic surf clam Spisula (=Mactromeris) polynyma by researchers from the Spanish PharmaMar group was first reported in 1999.

The molecule shows promise as an antiproliferative (anti-tumor) agent, and has intriguing mechanism of action. Cultured cells treated with spisulosine exhibit a greatly altered morphology. Examination of the cytoskeleton of the cells reveals the change is due to a loss of actin stress fibers, (bundles of actin filaments believed appear and disappear in response to mechanical stimuli). PharmaMar is presently directing Phase I clinical spisulosine trials in Europe.

The fact that the Arctic surf clam is a long-lived species (many 40+ year individuals exist in the wild populations) that is slow to reach reproductive maturity (at 5-8 years) will become an important factor if the decision is made in the future to expand commercial harvest to meet demand for supplies of spisulosine. Technologies emerging from current aquaculture efforts directed toward commercial production of the closely related Atlantic surf clam (S. solidissima) may be transferable to S. polynyma. so that a consistent, fast growing product can be developed for drug development purposes.

NCBI PubMed biomedical literature citations and abstracts - [ LINK ]

References

Cuadros R, Montejo de Garcini E, Wandosell F, Faircloth G, Fernandez-Sousa JM, and J Avila. 2000. The marine compound spisulosine, an inhibitor of cell proliferation, promotes the disassembly of actin stress fibers. Cancer Lett. 28:152:23-29.

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.

PharmaMar development pipeline summary:
http://www.pharmamar.es/en/pipeline/es285.cfm