Marine animal biosynthetic constituents for cancer chemotherapy.

A fifteen year investigation of marine animal components as sources for new and potentially useful cancer chemotherapeutic drugs has led to our discovery of a number of such valuable substance. The especially productive Indian Ocean sea hare Dolabella auricularia has yielded (100 kg leads to or approximately 1 mg each) a series of very potent cell growth inhibitory substances designated dolastatins 1-9. The first member of this new series, dolastatin 1, may represent the most potent anticancer agent so far uncovered with, e.g., a curative response (33%) using a dose of 11 microgram/kg (T/C 240, to T/C 139 at 1.37 microgram/kg) in the National Cancer Institute's murine B16 melanoma. Structural elucidation of the new antineoplastic agents is underway, and recent progress is illustrated with peptide dolastatin 3 (P388 ED 50 2.7 x 10(-7) microgram/ml).