Eribulin

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Eribulin
	File:Eribulin.svg
Clinical data
Trade names	Halaven
AHFS/Drugs.com	Consumer Drug Information
MedlinePlus	a611007
[[Regulation of therapeutic goods \|Template:Engvar data]]	US FDA: Eribulin;
Pregnancy; category	US: D (Evidence of risk) ; ;
Routes of; administration	Intravenous
ATC code	L01XX41 (WHO) ;
Legal status
Legal status	US: ℞-only ;
Identifiers
	IUPAC name 2-(3-Amino-2-hydroxypropyl)hexacosahydro-3-methoxy- 26-methyl-20,27-bis(methylene)11,15-18,21-24,28-triepoxy- 7,9-ethano-12,15-methano-9H,15H-furo(3,2-i)furo(2',3'-5,6) pyrano(4,3-b)(1,4)dioxacyclopentacosin-5-(4H)-one;
CAS Number	253128-41-5 ;
PubChem CID	17755248;
ChemSpider	21396142 ;
UNII	LR24G6354G;
ChEMBL	ChEMBL1237028 ;
E number	{{#property:P628}}
ECHA InfoCard	{{#property:P2566}}Lua error in Module:EditAtWikidata at line 36: attempt to index field 'wikibase' (a nil value).
Chemical and physical data
Formula	C40H59NO11
Molar mass	729.90 g/mol
3D model (JSmol)	Interactive image;
	SMILES NC[C@@H](O)C[C@H]5O[C@H]4C[C@H]9O[C@@H](CC[C@@H]1O[C@H](CC1=C)CC[C@@]32O[C@@H]6[C@@H]8O[C@H](C2)[C@H](O3)[C@@H]8O[C@H]7CC[C@H](CC(=O)O[C@@H]4[C@H]5OC)O[C@H]67)C[C@@H](C)C9=C;
	InChI InChI=1S/C39H57NO12/c1-18-11-22-5-7-25-19(2)12-24(44-25)9-10-39-16-30-35(51-39)36-37(49-30)38(52-39)33-26(48-36)8-6-23(46-33)14-31(42)50-34-29(15-27(45-22)20(18)3)47-28(32(34)43-4)13-21(41)17-40/h18,21-30,32-38,41H,2-3,5-17,40H2,1,4H3/t18-,21+,22+,23-,24+,25+,26+,27-,28-,29+,30-,32+,33+,34+,35+,36+,37-,38+,39+/m1/s1 ; Key:VEPHOPLDBFLPDL-KVWSPMLQSA-N ;
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

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.^[1] 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. ^[2]

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.^[3]

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 analogue of the marine sponge natural product halichondrin B,^[4]^[5] the latter being a potent naturally-occurring mitotic inhibitor with a unique mechanism of action found in the Halichondria genus of sponges.^[6]^[7] Eribulin is a mechanistically-unique inhibitor of microtubule dynamics,^[8]^[9] binding predominantly to a small number of high affinity sites at the plus ends of existing microtubules.^[10] Eribulin exerts its anticancer effects by triggering apoptosis of cancer cells following prolonged and irreversible mitotic blockade.^[11]^[12]

A new synthetic route to E7389 was published in 2009.^[13]

References

↑ "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
↑ http://www.clinicaltrials.gov/ct2/results?term=eribulin+OR+E7389
↑ Towle MJ, Salvato KA, Budrow J, Wels BF, Kuznetsov G, Aalfs KK, Welsh S, Zheng W, Seletsky BM, Palme MH, Habgood GJ, Singer LA, Dipietro LV, Wang Y, Chen JJ, Quincy DA, Davis A, Yoshimatsu K, Kishi Y, Yu MJ, Littlefield BA (2001). "In vitro and in vivo anticancer activities of synthetic macrocyclic ketone analogues of halichondrin B". Cancer Res. 61 (3): 1013–21. PMID 11221827. Unknown parameter |month= ignored (help)
↑ Yu MJ, Kishi Y, Littlefield BA (2005). "Discovery of E7389, a fully synthetic macrocyclic ketone analogue of halichondrin B". In Newman DJ, Kingston DGI, Cragg, GM. Anticancer agents from natural products. Washington, DC: Taylor & Francis. ISBN 0-8493-1863-7.
↑ Hirata Y, Uemura D (1986). "Halichondrins - antitumor polyether macrolides from a marine sponge". Pure Appl. Chem. 58 (5): 701–710. doi:10.1351/pac198658050701.
↑ Bai RL, Paull KD, Herald CL, Malspeis L, Pettit GR, Hamel E (1991). "Halichondrin B and homohalichondrin B, marine natural products binding in the vinca domain of tubulin. Discovery of tubulin-based mechanism of action by analysis of differential cytotoxicity data". J. Biol. Chem. 266 (24): 15882–9. PMID 1874739. Unknown parameter |month= ignored (help)
↑ Jordan MA, Kamath K, Manna T, Okouneva T, Miller HP, Davis C, Littlefield BA, Wilson L (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. Unknown parameter |month= ignored (help)
↑ Okouneva T, Azarenko O, Wilson L, Littlefield BA, Jordan MA (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. Unknown parameter |month= ignored (help)
↑ Smith JA, Wilson L, Azarenko O, Zhu X, Lewis BM, Littlefield BA, Jordan MA (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. Unknown parameter |month= ignored (help)
↑ Kuznetsov G, Towle MJ, Cheng H, Kawamura T, TenDyke K, Liu D, Kishi Y, Yu MJ, Littlefield BA (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. Unknown parameter |month= ignored (help)
↑ Towle MJ, Salvato KA, Wels BF, Aalfs KK, Zheng W, Seletsky BM, Zhu X, Lewis BM, Kishi Y, Yu MJ, Littlefield BA (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. Unknown parameter |month= ignored (help)
↑ Kim DS, Dong CG, Kim JT, Guo H, Huang J, Tiseni PS, Kishi Y (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. Unknown parameter |month= ignored (help)

External links

Eribulin Mesylate - Halaven (Brand Name Drug) (Original Approval Date FDA: November 15, 2010)

Template:Intracellular chemotherapeutic agents

Template:Antineoplastic-drug-stub

de:Eribulin

[1] "FDA approves new treatment option for late-stage breast cancer" (Press release). USFDA. 2010-11-15. Retrieved November 15, 2010.

[2] Notice of Decision for HALAVEN

[3] ttp://www.clinicaltrials.gov/ct2/results?term=eribulin+OR+E7389

[pmid11221827-4] Towle MJ, Salvato KA, Budrow J, Wels BF, Kuznetsov G, Aalfs KK, Welsh S, Zheng W, Seletsky BM, Palme MH, Habgood GJ, Singer LA, Dipietro LV, Wang Y, Chen JJ, Quincy DA, Davis A, Yoshimatsu K, Kishi Y, Yu MJ, Littlefield BA (2001). "In vitro and in vivo anticancer activities of synthetic macrocyclic ketone analogues of halichondrin B". Cancer Res. 61 (3): 1013–21. PMID 11221827. Unknown parameter |month= ignored (help)

[isbn0-8493-1863-7-5] Yu MJ, Kishi Y, Littlefield BA (2005). "Discovery of E7389, a fully synthetic macrocyclic ketone analogue of halichondrin B". In Newman DJ, Kingston DGI, Cragg, GM. Anticancer agents from natural products. Washington, DC: Taylor & Francis. ISBN 0-8493-1863-7.

[Hirata_1986-6] Hirata Y, Uemura D (1986). "Halichondrins - antitumor polyether macrolides from a marine sponge". Pure Appl. Chem. 58 (5): 701–710. doi:10.1351/pac198658050701.

[pmid1874739-7] Bai RL, Paull KD, Herald CL, Malspeis L, Pettit GR, Hamel E (1991). "Halichondrin B and homohalichondrin B, marine natural products binding in the vinca domain of tubulin. Discovery of tubulin-based mechanism of action by analysis of differential cytotoxicity data". J. Biol. Chem. 266 (24): 15882–9. PMID 1874739. Unknown parameter |month= ignored (help)

[pmid16020666-8] Jordan MA, Kamath K, Manna T, Okouneva T, Miller HP, Davis C, Littlefield BA, Wilson L (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. Unknown parameter |month= ignored (help)

[pmid18645010-9] Okouneva T, Azarenko O, Wilson L, Littlefield BA, Jordan MA (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. Unknown parameter |month= ignored (help)

[pmid20030375-10] Smith JA, Wilson L, Azarenko O, Zhu X, Lewis BM, Littlefield BA, Jordan MA (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. Unknown parameter |month= ignored (help)

[pmid15313917-11] Kuznetsov G, Towle MJ, Cheng H, Kawamura T, TenDyke K, Liu D, Kishi Y, Yu MJ, Littlefield BA (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. Unknown parameter |month= ignored (help)

[pmid21127197-12] Towle MJ, Salvato KA, Wels BF, Aalfs KK, Zheng W, Seletsky BM, Zhu X, Lewis BM, Kishi Y, Yu MJ, Littlefield BA (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. Unknown parameter |month= ignored (help)

[pmid19807076-13] Kim DS, Dong CG, Kim JT, Guo H, Huang J, Tiseni PS, Kishi Y (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. Unknown parameter |month= ignored (help)

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Eribulin

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Structure and mechanism

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