Halichondrin B
Encyclopedia
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
http://www.dtp.nci.nih.gov/timeline/noflash/success_stories/S4_halichondrinB.htm 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"http://www.dtp.nci.nih.gov/branches/btb/ivclsp.html. 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
was approved by the U.S. Food and Drug Administration on November 15, 2010, to treat patients with metastatic breast cancer who have received at least two prior chemotherapy regimens for late-stage disease, including both anthracycline- and taxane-based chemotherapies. Eribulin
is marketed by Eisai Co.
under the tradename Halaven.
Halichondria
Halichondria is a genus of marine demosponges belonging to the family Halichondriidae. These are massive, amorphous sponges with clearly separated inner and outer skeletons consisting of bundles of spicules arranged in a seemingly random pattern...
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
National Cancer Institute
The National Cancer Institute is part of the National Institutes of Health , which is one of 11 agencies that are part of the U.S. Department of Health and Human Services. The NCI coordinates the U.S...
http://www.dtp.nci.nih.gov/timeline/noflash/success_stories/S4_halichondrinB.htm and, in 1991, was the original test case for identification of mechanism of action (in this case, tubulin
Tubulin
Tubulin is one of several members of a small family of globular proteins. The most common members of the tubulin family are α-tubulin and β-tubulin, the proteins that make up microtubules. Each has a molecular weight of approximately 55 kiloDaltons. Microtubules are assembled from dimers of α- and...
-targeted mitotic inhibitor
Mitotic inhibitor
A mitotic inhibitor is a drug that inhibits mitosis, or cell division. These drugs disrupt microtubules, which are structures that pull the cell apart when it divides...
) by NCI's now famous but then-brand-new "60-cell line screen"http://www.dtp.nci.nih.gov/branches/btb/ivclsp.html. The complete chemical synthesis of halichondrin B, a large (MW = 1,110) polyether macrolide
Macrolide
The macrolides are a group of drugs whose activity stems from the presence of a macrolide ring, a large macrocyclic lactone ring to which one or more deoxy sugars, usually cladinose and desosamine, may be attached. The lactone rings are usually 14-, 15-, or 16-membered...
, was achieved by Yoshito Kishi
Yoshito Kishi
Yoshito Kishi is the Morris Loeb Professor of Chemistry at Harvard University. He is known for his contributions to the sciences of organic synthesis and total synthesis....
and colleagues at Harvard University
Harvard University
Harvard University is a private Ivy League university located in Cambridge, Massachusetts, United States, established in 1636 by the Massachusetts legislature. Harvard is the oldest institution of higher learning in the United States and the first corporation chartered in the country...
in 1992, an achievement that ultimately enabled the discovery and development of the structurally simplified and pharmaceutically optimized analog eribulin
Eribulin
Eribulin is an anticancer drug marketed by Eisai Co. under the trade name Halaven. Eribulin mesylate was approved by the U.S. Food and Drug Administration on November 15, 2010, to treat patients with metastatic breast cancer who have received at least two prior chemotherapy regimens for late-stage...
(E7389, ER-086526, NSC-707389). Eribulin
Eribulin
Eribulin is an anticancer drug marketed by Eisai Co. under the trade name Halaven. Eribulin mesylate was approved by the U.S. Food and Drug Administration on November 15, 2010, to treat patients with metastatic breast cancer who have received at least two prior chemotherapy regimens for late-stage...
was approved by the U.S. Food and Drug Administration on November 15, 2010, to treat patients with metastatic breast cancer who have received at least two prior chemotherapy regimens for late-stage disease, including both anthracycline- and taxane-based chemotherapies. Eribulin
Eribulin
Eribulin is an anticancer drug marketed by Eisai Co. under the trade name Halaven. Eribulin mesylate was approved by the U.S. Food and Drug Administration on November 15, 2010, to treat patients with metastatic breast cancer who have received at least two prior chemotherapy regimens for late-stage...
is marketed by Eisai Co.
Eisai Co.
is a Japanese pharmaceutical company, ranking among the top 25 in the world by revenue and achieving $8 billion USD in sales for the fiscal 2008 year. Headquartered in Tokyo, Japan, it has some 10,000 employees, among them about 1,500 in research. Eisai is a member of the Topix 100 and Nikkei 225...
under the tradename Halaven.