NAAMIDINE-A IS AN ANTAGONIST OF THE EPIDERMAL GROWTH-FACTOR RECEPTOR AND AN IN-VIVO ACTIVE ANTITUMOR AGENT

The known 2-aminoimidazole alkaloid naamidine A (1) was isolated from a Fijian Leucetta sp. sponge as an inhibitor of the epidermal growth f actor (EGF) receptor. The compound exhibited potent ability to inhibit the EGF signaling pathway and is morespecific for the EGF-mediated mi togenic response than for the insulin-mediated mitogenic response. Eva luation in an A431 xenograft tumor model in athymic mice indicated tha t naamidine A exhibited at least 85% growth inhibition at the maximal tolerated dose of 25 mg/kg. Preliminary mechanism of action studies in dicate that the alkaloid fails to inhibit the binding of EGF to the re ceptor and has no effect on the catalytic activity of purified c-src t yrosine kinase.