Eribulin
Encyclopedia
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 disease, including both anthracycline
- and taxane
-based chemotherapies
.
Eribulin is also being investigated by Eisai Co. for use in a variety of other solid tumors, including non-small cell lung cancer, prostate cancer
and sarcoma
.
Eribulin has been previously known as E7389 and ER-086526, and also carries the US NCI designation NSC-707389.
of the marine sponge natural product halichondrin B
, the latter being a potent naturally-occurring mitotic inhibitor
with a unique mechanism of action
found in the Halichondria
genus of sponge
s. Eribulin is a mechanistically-unique inhibitor of microtubule dynamics, binding predominantly to a small number of high affinity sites at the plus ends of existing microtubules. Eribulin exerts its anticancer effects by triggering apoptosis of cancer cells following prolonged and irreversible mitotic blockade.
A new synthetic route to E7389 was published in 2009.
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 trade name Halaven. Eribulin mesylate
Mesylate
In chemistry, a mesylate is any salt or ester of methanesulfonic acid . In salts, the mesylate is present as the CH3SO3− anion. When modifying the International Nonproprietary Name of a pharmaceutical substance containing the group or anion, the correct spelling is mesilate .Mesylate esters are a...
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
Anthracycline
Anthracyclines are a class of drugs used in cancer chemotherapy derived from Streptomyces bacterium Streptomyces peucetius var...
- and taxane
Taxane
The taxanes are diterpenes produced by the plants of the genus Taxus . As their name suggests, they were first derived from natural sources, but some have been synthesized artificially. Taxanes include paclitaxel and docetaxel . Paclitaxel was originally derived from the Pacific yew tree.Taxanes...
-based chemotherapies
Chemotherapy
Chemotherapy is the treatment of cancer with an antineoplastic drug or with a combination of such drugs into a standardized treatment regimen....
.
Eribulin is also being investigated by Eisai Co. for use in a variety of other solid tumors, including non-small cell lung cancer, prostate cancer
Prostate cancer
Prostate cancer is a form of cancer that develops in the prostate, a gland in the male reproductive system. Most prostate cancers are slow growing; however, there are cases of aggressive prostate cancers. The cancer cells may metastasize from the prostate to other parts of the body, particularly...
and sarcoma
Sarcoma
A sarcoma is a cancer that arises from transformed cells in one of a number of tissues that develop from embryonic mesoderm. Thus, sarcomas include tumors of bone, cartilage, fat, muscle, vascular, and hematopoietic tissues...
.
Eribulin has been previously known as E7389 and ER-086526, and also carries the US NCI designation NSC-707389.
Structure and mechanism
Structurally, eribulin is a fully synthetic macrocyclic ketone analogueAnalog (chemistry)
In chemistry, a structural analog , also known as chemical analog or simply analog, is a compound having a structure similar to that of another one, but differing from it in respect of a certain component. It can differ in one or more atoms, functional groups, or substructures, which are replaced...
of the marine sponge natural product halichondrin B
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...
, the latter being a potent naturally-occurring 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...
with a unique mechanism of action
Mechanism of action
In pharmacology, the term mechanism of action refers to the specific biochemical interaction through which a drug substance produces its pharmacological effect...
found in the Halichondria
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...
genus of sponge
Demosponge
The Demospongiae are the largest class in the phylum Porifera. Their "skeletons" are made of spicules consisting of fibers of the protein spongin, the mineral silica, or both. Where spicules of silica are present, they have a different shape from those in the otherwise similar glass sponges...
s. Eribulin is a mechanistically-unique inhibitor of microtubule dynamics, binding predominantly to a small number of high affinity sites at the plus ends of existing microtubules. Eribulin exerts its anticancer effects by triggering apoptosis of cancer cells following prolonged and irreversible mitotic blockade.
A new synthetic route to E7389 was published in 2009.