|AHFS/Drugs.com||Consumer Drug Information|
|ATC code||L01XX41 (WHO)|
|Chemical and physical data|
|Molar mass||729.90 g/mol|
|3D model (Jmol)||Interactive image|
|(what is this?)|
Eribulin is an anticancer drug marketed by Eisai Co. under the trade name Halaven. Eribulin is also known as E7389 and ER-086526, and also carries the US NCI designation NSC-707389. It is used to treat certain patients with breast cancer and liposarcoma.
Approvals and indications
The mesylate salt 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. It was approved by Health Canada on December 14, 2011, for treatment of patients with metastatic breast cancer who have previously received at least two chemotherapeutic regimens for the treatment of metastatic disease.
In January 2016 the US FDA approved Halaven for the treatment of inoperable liposarcoma in patients who received prior chemotherapy that contained an anthracycline drug. A phase III trial reported: With Halaven the median overall survival for patients with liposarcoma was 15.6 months, compared to 8.4 months for patients treated with dacarbazine.
Structure and mechanism
Eribulin is a fully synthetic macrocyclic analogue of the marine natural product halichondrin B, the parent molecule being a potent naturally occurring mitotic inhibitor with a unique mechanism of action found in the Halichondria genus of sponges.
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.
- "FDA approves new treatment option for late-stage breast cancer" (Press release). USFDA. 2010-11-15. Retrieved November 15, 2010.
- Notice of Decision for HALAVEN
- FDA approves first drug to show survival benefit in liposarcoma. Jan 2016
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- Jordan MA, Kamath K, Manna T, Okouneva T, Miller HP, Davis C, Littlefield BA, Wilson L (July 2005). "The primary antimitotic mechanism of action of the synthetic halichondrin E7389 is suppression of microtubule growth". Mol. Cancer Ther. 4 (7): 1086–95. doi:10.1158/1535-7163.MCT-04-0345. PMID 16020666.
- Okouneva T, Azarenko O, Wilson L, Littlefield BA, Jordan MA (July 2008). "Inhibition of Centromere Dynamics by Eribulin (E7389) during Mitotic Metaphase". Mol. Cancer Ther. 7 (7): 2003–11. doi:10.1158/1535-7163.MCT-08-0095. PMC 2562299. PMID 18645010.
- Smith JA, Wilson L, Azarenko O, Zhu X, Lewis BM, Littlefield BA, Jordan MA (February 2010). "Eribulin Binds at Microtubule Ends to a Single Site on Tubulin to Suppress Dynamic Instability". Biochemistry. 49 (6): 1331–7. doi:10.1021/bi901810u. PMC 2846717. PMID 20030375.
- Wilson, L; Lopus, M; Miller, HP; Azarenko, O; Riffle, S; Smith, JA; Jordan, MA (2015). "Effects of eribulin on microtubule binding and dynamic instability are strengthened in the absence of the βIII tubulin isotype". Biochemistry. 54: 6482–9. doi:10.1021/acs.biochem.5b00745. PMID 26435331.
- Kuznetsov G, Towle MJ, Cheng H, Kawamura T, TenDyke K, Liu D, Kishi Y, Yu MJ, Littlefield BA (August 2004). "Induction of morphological and biochemical apoptosis following prolonged mitotic blockage by halichondrin B macrocyclic ketone analog E7389". Cancer Res. 64 (16): 5760–6. doi:10.1158/0008-5472.CAN-04-1169. PMID 15313917.
- Towle MJ, Salvato KA, Wels BF, Aalfs KK, Zheng W, Seletsky BM, Zhu X, Lewis BM, Kishi Y, Yu MJ, Littlefield BA (January 2011). "Eribulin induces irreversible mitotic blockade: implications of cell-based pharmacodynamics for in vivo efficacy under intermittent dosing conditions". Cancer Res. 71 (2): 496–505. doi:10.1158/0008-5472.CAN-10-1874. PMID 21127197.
- Kim DS, Dong CG, Kim JT, Guo H, Huang J, Tiseni PS, Kishi Y (November 2009). "New syntheses of E7389 C14-C35 and halichondrin C14-C38 building blocks: double-inversion approach". J. Am. Chem. Soc. 131 (43): 15636–41. doi:10.1021/ja9058475. PMID 19807076.