ABSTRACT
HTI-286 (1) is a synthetic experimental anticancer drug that progressed to phase II clinical trials for the treatment of nonsmall-cell lung cancer.1 It shows activity in a wide variety of tumor xenograft models, including several multidrug-resistant tumors. The lead structure for the development of HTI-286 was the sponge tripeptide hemiasterlin (2), a microtubule depolymerizing agent that kills cells by causing mitotic arrest leading to apoptosis. The sequence of discoveries that led to the development of HTI-286 and a proœle of its biological activities are described next.
