The marine natural product, halistanol trisulfate, inhibits pp60v-src protein tyrosine kinase activity.

ABSTRACT

Halistanol trisulfate, a sulfated steroid derivative, was isolated from the extracts of two different marine sponges (genus Topsentia) by bioassay-guided fractionation. It exhibited an IC50 of approximately 4 microM against pp60v-src, the oncogenic protein tyrosine kinase encoded by Rous sarcoma virus. Removing the sulfate groups by acid hydrolysis produced the inactive tris-alcohol, halistanol. The kinetics of inhibition were examined and revealed that halistanol trisulfate is a competitive inhibitor with respect to the peptide substrate, [val5]-angiotensin II, and a mixed inhibitor with respect to ATP. A number of monosulfated steroids were studied for protein tyrosine kinase inhibitory activity, but were found to be inactive.