Halichondrin B

Halichondrin B is a naturally-occurring compound originally isolated from the marine sponge Halichondria okadai by Hirata and Uemura in 1986. In the same report, these authors also reported the exquisite anticancer activity of halichondrin B against murine cancer cells both in culture and in in vivo studies. Halichondrin B was highly prioritized for development as a novel anticancer therapeutic by the United States National Cancer Institute and, in 1991, was the original test case for identification of mechanism of action (in this case, tubulin-targeted mitotic inhibitor) by NCI's now famous but then-brand new "60-cell line screen". The complete chemical synthesis of halichondrin B, a large (MW = 1,110) polyether macrolide, was achieved by Yoshito Kishi and colleagues at Harvard University in 1992, an achievement that ultimately enabled the discovery and development of the structurally-simplified and pharmaceutically-optimized analog eribulin (E7389, ER-086526, NSC-707389). Eribulin is currently being investigated by Eisai Co. for the third-line treatment of advanced breast cancer in patients who have been previously treated with anthracyclines, taxanes and capecitabine, as well as a variety of other solid tumors, including non-small cell lung cancer, prostate cancer and sarcoma.