Halichondrin B is a

polyether In organic chemistry, ethers are a class of compounds that contain an ether group—an oxygen atom connected to two alkyl or aryl groups. They have the general formula , where R and R′ represent the alkyl or aryl groups. Ethers can again be c ...

macrolide The Macrolides are a class of natural products that consist of 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. Macrol ...

originally isolated from the marine sponge ''

Halichondria ''Halichondria'' is a genus of sea sponges 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 An anticarcinogen (also known as a carcinopreventive agent) is a substance that counteracts the effects of a carcinogen or inhibits the development of cancer. Anticarcinogens are different from anticarcinoma agents (also known as anticancer or an ...

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

therapeutic by the United States

National Cancer Institute The National Cancer Institute (NCI) coordinates the United States National Cancer Program and is part of the National Institutes of Health (NIH), which is one of eleven agencies that are part of the U.S. Department of Health and Human Services. ...

and, in 1991, was the original test case for identification of mechanism of action (in this case,

tubulin Tubulin in molecular biology can refer either to the tubulin protein superfamily of globular proteins, or one of the member proteins of that superfamily. α- and β-tubulins polymerize into microtubules, a major component of the eukaryotic cytoske ...

-targeted

mitotic inhibitor A mitotic inhibitor is a drug that inhibits mitosis, or cell division. These drugs disrupt microtubules, which are structures that pull the chromosomes apart when a cell divides. Mitotic inhibitors are used in cancer treatment, because cancer cell ...

) by NCI's then-brand-new " 60-cell line screen" The complete chemical synthesis of halichondrin B was achieved by

Yoshito Kishi is a Japanese chemist who 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. Kishi was born in Nagoya, Japan and attended Nagoya Universi ...

and colleagues at

Harvard University Harvard University is a private Ivy League research university in Cambridge, Massachusetts. Founded in 1636 as Harvard College and named for its first benefactor, the Puritan clergyman John Harvard, it is the oldest institution of higher le ...

in 1992, an achievement that ultimately enabled the discovery and development of the structurally simplified and pharmaceutically optimized analog

eribulin Eribulin, sold under the brand name Halaven, is an anticancer medication used to treat breast cancer and liposarcoma. The most common side effects include fatigue, nausea, hair loss (alopecia), constipation, certain nerve damage causing weaknes ...

(E7389, ER-086526, NSC-707389).

Eribulin Eribulin, sold under the brand name Halaven, is an anticancer medication used to treat breast cancer and liposarcoma. The most common side effects include fatigue, nausea, hair loss (alopecia), constipation, certain nerve damage causing weaknes ...

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.

is marketed by

Eisai Co. is a Japanese pharmaceutical company headquartered in Tokyo, Japan. It has some 10,000 employees, among them about 1,500 in research. Eisai is listed on the Tokyo Stock Exchange and is a member of the Topix 100 and Nikkei 225 stock indices. ...

under the tradename Halaven.

Biosynthesis

While a producer organism for Halichondrin B has never been isolated in pure culture, the structural features of Halichondrin B, such as the 'odd-even' rule of methylation, and the abundance of oxygen heterocycles, suggest it is a product of dinoflagellate polyether metabolism. In support of this conjecture, the known dinoflagellate toxin

okadaic acid Okadaic acid, C44H68O13, is a toxin produced by several species of dinoflagellates, and is known to accumulate in both marine sponges and shellfish. One of the primary causes of diarrhetic shellfish poisoning, okadaic acid is a potent inhibitor of ...

was isolated from the same species of sponge.

References

{{reflist, 2 Macrolides Polyether toxins