Discovery of E7389, A Fully Synthetic Macrocyclic Ketone Analog of Halichondrin B

E7389, a fully synthetic analog of the structurally complex marine natural product halichondrin B (HB), exhibits unique effects on tubulin dynamics, along with striking anticancer activity in preclinical models of human cancer. The nature of E7389’s antitumor activity in such models, combined with its novel tubulin-based effects and superiority over paclitaxel in several animal models, indicates that this agent may exhibit a unique spectrum of antitumor activities in the clinic that will differentiate it from existing anticancer drugs.