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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 (February 2001). "In vitro and in vivo anticancer activities of synthetic macrocyclic ketone analogues of halichondrin B". Cancer Res. 61 (3): 1013–21. PMID 11221827.
^ 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 (August 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.
^ 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.
^ 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.

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1. 転移性乳癌の全身治療：単剤化学療法 systemic treatment for metastatic breast cancer single agent chemotherapy
2. 肝疾患を有する患者における化学療法による肝毒性および用量調整 chemotherapy hepatotoxicity and dose modification in patients with liver disease
3. 非プラチナ製剤ベースの癌化学療法の神経学的合併症 neurologic complications of non platinum cancer chemotherapy
4. 化学療法関連腎毒性および腎不全患者における用量調整 chemotherapy related nephrotoxicity and dose modification in patients with renal insufficiency
5. アントラサイクリン系以外の癌化学療法剤の心毒性 cardiotoxicity of nonanthracycline cancer chemotherapy agents

English Journal

Body Mass Index and Treatment Outcomes in Metastatic Breast Cancer Patients Treated With Eribulin.

Barba M1,2, Pizzuti L1, Sperduti I3, Natoli C4, Gamucci T5, Sergi D1, Di Lauro L1, Moscetti L6, Izzo F1, Rinaldi M1, Mentuccia L5, Vaccaro A5, Iezzi L4, Grassadonia A4, Michelotti A7, Landucci E7, Perracchio L8, Pescarmona E8, Di Filippo F9, Giordano A10,11, Maugeri-Saccà M1,2, Vici P1.
Journal of cellular physiology.J Cell Physiol.2016 May;231(5):986-91. doi: 10.1002/jcp.25213. Epub 2015 Nov 20.
Eribulin has shown survival advantage and manageable toxicity in heavily pre-treated metastatic breast cancer (mBC). We assessed whether body mass index (BMI) impacts treatment outcomes in 101 patients treated with eribulin at six Italian Oncologic Centers. BMI was addressed as a categorical variabl
PMID 26449308

Practical experiences with eribulin in patients with metastatic breast cancer.

Tesch H1, Schneeweiss A.
Anti-cancer drugs.Anticancer Drugs.2016 Feb;27(2):112-7. doi: 10.1097/CAD.0000000000000288.
There is currently no standard therapy for women with metastatic or locally recurrent breast cancer. The microtubule polymerization inhibitor eribulin, approved in March 2011, is the first monochemotherapy with a proven survival benefit and tolerable toxicity in this patient group. Using a retrospec
PMID 26488444

Therapeutic intervention based on circulating tumor cell phenotype in metastatic breast cancer: concept of the DETECT study program.

Schramm A1, Friedl TW2, Schochter F2, Scholz C2, de Gregorio N2, Huober J2, Rack B3, Trapp E3, Alunni-Fabbroni M3, Müller V4, Schneeweiss A5, Pantel K6, Meier-Stiegen F7, Hartkopf A8, Taran FA8, Wallwiener D8, Janni W2, Fehm T7.
Archives of gynecology and obstetrics.Arch Gynecol Obstet.2016 Feb;293(2):271-81. doi: 10.1007/s00404-015-3879-7. Epub 2015 Sep 9.
PURPOSE: The aim of the ongoing DETECT study program is to evaluate therapeutic intervention based on phenotypes of circulating tumor cells (CTC) in patients with metastatic breast cancer (MBC). Currently (as of July 2015) more than half of the projected about 2000 patients with MBC have already bee
PMID 26354331

Japanese Journal

エリブリンに関する臨床試験 (第5土曜特集日本のがん診療UPDATE : 連携拠点病院と最新トピックス) -- (日本から研究がはじまって承認された抗がん剤 : 開発の経緯から現状まで)

医学のあゆみ 254(9), 784-788, 2015-08-29
NAID 40020570246

症例報告 9次治療として施行したEribulin,Trastuzumab,Pertuzumabの併用療法が奏効している骨・腹腔リンパ節転移を有する多剤耐性HER2陽性再発乳癌の1例

京都府立医科大学雑誌 123(9), 633-639, 2014-09
NAID 40020224321

乳がんに対する新規抗がん剤エリブリンの可能性

腫瘍内科 13(3), 384-391, 2014-03
NAID 40020035835

Related Pictures

理化学的知見 Halaven(eribulin mesy Eribulin mesylate: agent that is called eribulin Eribulin – ein Hoffnungsträger bei Eribulin - click for 3D structure file File:Eribulin.svg Eribulin Cost

★リンクテーブル★

リンク元

「エリブリン」

Eribulin
Systematic (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
Clinical data
Trade names	Halaven
AHFS/Drugs.com	Consumer Drug Information
MedlinePlus	a611007
Licence data	US FDA:link
Pregnancy cat.	US: D;
Legal status	US: ℞-only;
Routes	Intravenous
Identifiers
CAS number	253128-41-5
ATC code	L01XX41
PubChem	CID 17755248
ChemSpider	21396142
UNII	LR24G6354G
ChEMBL	CHEMBL1237028
Chemical data
Formula	C40H59NO11
Mol. mass	729.90 g/mol
	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)OC@@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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　　[★]

英: eribulin
商: ハラヴェン Halaven
化: エリブリンメシル酸塩 eribulin mesilate
関: その他の腫瘍用薬

[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 (February 2001). "In vitro and in vivo anticancer activities of synthetic macrocyclic ketone analogues of halichondrin B". Cancer Res. 61 (3): 1013–21. PMID 11221827.

[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 (August 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.

[pmid16020666-8] 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.

[pmid18645010-9] 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.

[pmid20030375-10] 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.

[pmid15313917-11] 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.

[pmid21127197-12] 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.

[pmid19807076-13] 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.

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eribulin