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Revision as of 11:20, 17 November 2011 editBeetstra (talk | contribs)Edit filter managers, Administrators172,031 edits Saving copy of the {{drugbox}} taken from revid 457062983 of page Eribulin for the Chem/Drugbox validation project (updated: 'ChEMBL', 'CAS_number').  Latest revision as of 03:55, 10 July 2024 edit Whywhenwhohow (talk | contribs)Autopatrolled, Extended confirmed users, Pending changes reviewers49,153 edits update refs 
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{{Short description|Pharmaceutical drug}}
{{ambox | text = This page contains a copy of the infobox ({{tl|drugbox}}) taken from revid of page ] with values updated to verified values.}}
{{Use dmy dates|date=February 2024}}
{{Drugbox
{{cs1 config |name-list-style=vanc |display-authors=6}}
{{Infobox drug
| Verifiedfields = changed | Verifiedfields = changed
| verifiedrevid = 461094948
| Watchedfields = changed
| verifiedrevid = 400703367
| 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-9''H'',15''H''-furo(3,2-i)furo(2',3'-5,6) pyrano(4,3-b)(1,4)dioxacyclopentacosin-5-(4''H'')-one
| image = Eribulin.svg | image = Eribulin.svg
| width = 300 | width = 300
| alt =
| caption =
| USAN = eribulin mesylate
| JAN = eribulin mesilate


<!--Clinical data--> <!-- Clinical data -->
| tradename = | pronounce =
| tradename = Halaven, Mevlyq
| Drugs.com = {{drugs.com|CDI|eribulin}}
| Drugs.com = {{drugs.com|monograph|eribulin-mesylate}}
| MedlinePlus = a611007 | MedlinePlus = a611007
| DailyMedID = Eribulin
| licence_EU = <!-- EMEA requires brand name -->
| pregnancy_AU = D
| licence_US = Eribulin
| pregnancy_AU_comment = <ref name="Drugs.com pregnancy">{{cite web | title=Eribulin (Halaven) Use During Pregnancy | website=Drugs.com | date=22 October 2019 | url=https://www.drugs.com/pregnancy/eribulin.html | access-date=9 July 2020}}</ref>
| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X -->
| pregnancy_US = D | pregnancy_category =
| routes_of_administration = ]
| pregnancy_category =
| class = ]
| legal_AU = <!-- S2, S3, S4, S5, S6, S7, S8, S9 or Unscheduled-->
| ATC_prefix = L01
| legal_CA = <!-- Schedule I, II, III, IV, V, VI, VII, VIII -->
| ATC_suffix = XX41
| legal_UK = <!-- GSL, P, POM, CD, or Class A, B, C -->
| ATC_supplemental =

<!-- Legal status -->
| legal_AU = S4
| legal_AU_comment =
| legal_BR = <!-- OTC, A1, A2, A3, B1, B2, C1, C2, C3, C4, C5, D1, D2, E, F -->
| legal_BR_comment =
| legal_CA = Rx-only
| legal_CA_comment = <ref name="CA Halaven PI" />
| legal_DE = <!-- Anlage I, II, III or Unscheduled -->
| legal_DE_comment =
| legal_NZ = <!-- Class A, B, C -->
| legal_NZ_comment =
| legal_UK = POM
| legal_UK_comment = <ref>{{cite web | title=Halaven 0.44 mg/ml solution for injection | website=(emc) | date=16 January 2023 | url=https://www.medicines.org.uk/emc/product/4517/smpc | access-date=16 December 2023}}</ref>
| legal_US = Rx-only | legal_US = Rx-only
| legal_US_comment = <ref name="Halaven FDA label" />
| legal_status =
| legal_EU = Rx-only
| routes_of_administration = Intravenous
| legal_EU_comment = <ref name="Halaven EPAR">{{cite web | title=Halaven EPAR | website=] (EMA) | date=17 March 2011 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/halaven | access-date=16 December 2023}}</ref><ref name="Mevlyq EPAR">{{cite web | title=Mevlyq EPAR | website=] (EMA) | date=9 February 2024 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/mevlyq | access-date=19 February 2024}}</ref><ref>{{cite web | title=Mevlyq product information | website=Union Register of medicinal products | date=13 February 2024 | url=https://ec.europa.eu/health/documents/community-register/html/h1789.htm | access-date=19 February 2024}}</ref>
| legal_UN = <!-- N I, II, III, IV / P I, II, III, IV -->
| legal_UN_comment =
| legal_status = Rx-only<ref>{{cite press release | title=Eisai Announces Japan Launch Of Anticancer Agent Halaven | publisher=Eisai Co., Ltd. | date=19 July 2011 | url=https://www.eisai.com/news/news201155.html | access-date=15 February 2021}}</ref><ref>{{cite press release | title=Anticancer Agent Halaven Approved For Treatment Of Locally Advanced Or Metastatic Breast Cancer In China | publisher=Eisai Co., Ltd. | date=17 July 2019 | url=https://www.eisai.com/news/2019/news201952.html | access-date=15 February 2021}}</ref>


<!--Pharmacokinetic data--> <!-- Pharmacokinetic data -->
| bioavailability = | bioavailability =
| protein_bound = | protein_bound =
| metabolism = | metabolism =
| metabolites =
| elimination_half-life =
| excretion = | onset =
| elimination_half-life =
| duration_of_action =
| excretion =


<!--Identifiers--> <!-- Identifiers -->
| CAS_number_Ref = {{cascite|correct|??}} | CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = <!-- blanked - oldvalue: 253128-41-5 --> | CAS_number = 253128-41-5
| ATC_prefix = L01 | CAS_supplemental =
| ATC_suffix = XX41 | PubChem = 11354606
| ATC_supplemental = | IUPHAR_ligand =
| PubChem = 17755248
| DrugBank_Ref = {{drugbankcite|correct|drugbank}} | DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = | DrugBank = DB08871
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} | ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 21396142 | ChemSpiderID = 24721813
| UNII_Ref = {{fdacite|changed|FDA}} | UNII_Ref = {{fdacite|correct|FDA}}
| UNII = LR24G6354G | UNII = LR24G6354G
| KEGG_Ref =
| ChEMBL_Ref = {{ebicite|changed|EBI}}
| KEGG = D08914
| ChEMBL = <!-- blanked - oldvalue: 1237028 -->
| chemical_formula = | ChEBI_Ref =
| ChEBI = 63587
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 1683590
| NIAID_ChemDB =
| PDB_ligand =
| synonyms = E7389, ER-086526, NSC-707389

<!-- Chemical and physical data -->
| 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-9''H'',15''H''-furo(3,2-i)furo(2',3'-5,6) pyrano(4,3-b)(1,4)dioxacyclopentacosin-5-(4''H'')-one
| C=40 | H=59 | N=1 | O=11 | C=40 | H=59 | N=1 | O=11
| SMILES = CC1CC2CCC3C(=C)CC(O3)CCC45CC6C(O4)C7C(O6)C(O5)C8C(O7)CCC(O8)CC(=O)CC9C(CC(C1=C)O2)OC(C9OC)CC(CN)O
| molecular_weight = 729.90 g/mol
| smiles = NC(O)C5O4C9O(CC1O(CC1=C)CC32O68O(C2)(O3)8O7CC(CC(=O)O45OC)O67)C(C)C9=C
| InChI = 1/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
| InChIKey = VEPHOPLDBFLPDL-KVWSPMLQBN
| StdInChI_Ref = {{stdinchicite|correct|chemspider}} | StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 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 | StdInChI = 1S/C40H59NO11/c1-19-11-24-5-7-28-20(2)12-26(45-28)9-10-40-17-33-36(51-40)37-38(50-33)39(52-40)35-29(49-37)8-6-25(47-35)13-22(42)14-27-31(16-30(46-24)21(19)3)48-32(34(27)44-4)15-23(43)18-41/h19,23-39,43H,2-3,5-18,41H2,1,4H3/t19-,23+,24+,25-,26+,27+,28+,29+,30-,31+,32-,33-,34-,35+,36+,37+,38-,39+,40+/m1/s1
| StdInChI_comment =
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} | StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = VEPHOPLDBFLPDL-KVWSPMLQSA-N | StdInChIKey = UFNVPOGXISZXJD-JBQZKEIOSA-N
| density =
| density_notes =
| melting_point =
| melting_high =
| melting_notes =
| boiling_point =
| boiling_notes =
| solubility =
| sol_units =
| specific_rotation =
}} }}

'''Eribulin''', sold under the brand name '''Halaven''' among others, is an ] used to treat ] and ].<ref name="Halaven FDA label">{{cite web | title=Halaven- eribulin mesylate injection | website=DailyMed | date=22 December 2017 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=31ce4750-ded5-4a0b-95e9-f229fa6bc822 | access-date=9 July 2020}}</ref><ref name="Halaven EPAR" />

The most common side effects include fatigue, nausea, hair loss (alopecia), constipation, certain nerve damage causing weakness or numbness in the hands and feet (peripheral neuropathy), abdominal pain and fever (pyrexia).<ref name="FDA-lipo2016" /> Eribulin may also cause low levels of infection-fighting white blood cells (neutropenia) or decreased levels of potassium or calcium.<ref name="FDA-lipo2016" />

Eribulin was approved for medical use in the United States in November 2010,<ref>{{cite web | title=Drug Approval Package: Halaven (erbulin mesylate) NDA 201532 | website=U.S. ] (FDA) | url=https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/201532s000_halaven_TOC.cfm | access-date=9 July 2020}}</ref> the European Union in March 2011,<ref name="Halaven EPAR" /> and Canada in December 2011.<ref name="CA Halaven PI">{{cite web | title=Halaven Product information | website=] | date=22 October 2009 | url=https://health-products.canada.ca/dpd-bdpp/info?lang=eng&code=86314 | access-date=16 December 2023}}</ref><ref>{{cite web | title=Halaven for Metastatic Breast Cancer | website=Canadian Agency for Drugs and Technologies in Health | date=9 March 2015 | url=https://www.cadth.ca/halaven-metastatic-breast-cancer-details | access-date=9 July 2020}}</ref><ref>{{cite press release | title=Eisai Announces Canadian Approval of its Anticancer Agent Halaven | website=Eisai Co., Ltd. | url=https://www.eisai.com/news/news201179.html | access-date=9 July 2020}}</ref> It is available as a ].<ref name="Mevlyq EPAR" />

== Medical uses ==
Eribulin is ] for the treatment of people with locally advanced or metastatic breast cancer,<ref name="Halaven EPAR" /><ref>{{cite press release | title = FDA approves new treatment option for late-stage breast cancer | publisher = U.S. ] (FDA) | date = 15 November 2010 | url = https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm233863.htm | access-date = 15 November 2010 | archive-url = https://web.archive.org/web/20101117013510/http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm233863.htm | archive-date = 17 November 2010 | url-status = dead }}</ref><ref>{{cite web | title=Eribulin | website=U.S. Food and Drug Administration | date=28 January 2016 | url=https://www.fda.gov/drugs/resources-information-approved-drugs/eribulin | access-date=16 December 2023}}</ref><ref>{{dead link|date=September 2017 |bot=InternetArchiveBot |fix-attempted=yes }}</ref><ref>{{cite web | title=Halaven for Metastatic Breast Cancer | website=Canadian Agency for Drugs and Technologies in Health | date=9 March 2015 | url=https://www.cadth.ca/halaven-metastatic-breast-cancer-details | access-date=9 July 2020}}</ref><ref>{{cite press release | title=Eisai Announces Canadian Approval of its Anticancer Agent Halaven | website=Eisai Co., Ltd. | url=https://www.eisai.com/news/news201179.html | access-date=9 July 2020}}</ref> and for the treatment of adults with unresectable liposarcoma.<ref name="Halaven EPAR" /><ref name="FDA-lipo2016">{{cite press release | title=FDA approves first drug to show survival benefit in liposarcoma | website=U.S. ] (FDA) | date=28 January 2016 | url=https://www.fda.gov/news-events/press-announcements/fda-approves-first-drug-show-survival-benefit-liposarcoma | access-date=9 July 2020}} {{PD-notice}}</ref><ref>{{cite press release | title=U.S. FDA Approves Eisai's Anticancer Agent Halaven For The Treatment Of Advanced Liposarcoma | publisher=Eisai Co., Ltd. | date=29 January 2016 | url=https://www.eisai.com/news/news201604.html | access-date=15 February 2021}}</ref>

== Adverse effects ==
Serious side effects may include anaemia; decrease in white blood cell count, which can increase the risk of serious infections that could lead to death; hair loss; cancer-related fatigue; numbness, tingling or burning in the hands and feet (neuropathy); harm to a developing fetus; as well as changes in heartbeat (QTc prolongation), that may also lead to death.<ref name="FDA-lipo2016" /><ref>{{cite web |date=5 June 2015 |title=Eribulin (Halaven) |url=https://breastcancernow.org/information-support/facing-breast-cancer/going-through-treatment-breast-cancer/chemotherapy/eribulin-halaven |access-date=15 September 2022 |website=Breast Cancer Now }}</ref>{{Unreliable medical source|date=December 2023}}

==Structure and mechanism==
Eribulin is a fully synthetic ] ] ] of the marine ] ],<ref name="pmid11221827">{{cite journal | vauthors = 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 | title = In vitro and in vivo anticancer activities of synthetic macrocyclic ketone analogues of halichondrin B | journal = Cancer Research | volume = 61 | issue = 3 | pages = 1013–21 | date = February 2001 | pmid = 11221827 }}</ref><ref name="isbn0-8493-1863-7">{{cite book | veditors = Newman DJ, Kingston DG, Cragg GM | title = Anticancer agents from natural products | publisher = Taylor & Francis | location = Washington, DC | year = 2005 | chapter = Discovery of E7389, a fully synthetic macrocyclic ketone analogue of halichondrin B | vauthors = Yu MJ, Kishi Y, Littlefield BA | author-link2 = Yoshito Kishi | isbn = 978-0-8493-1863-4 }}{{page needed|date=November 2017}}</ref> the parent molecule being a naturally occurring, potent ] with a unique ]. The parent molecule was originally found in the ] ''] okadai''.<ref name = "Hirata_1986">{{cite journal| vauthors = Hirata Y, Uemura D |date=1 January 1986|title=Halichondrins - antitumor polyether macrolides from a marine sponge|journal=Pure and Applied Chemistry|volume=58|issue=5|pages=701–710|doi=10.1351/pac198658050701|s2cid=38138047 |issn=1365-3075|doi-access = free | title-link = doi }}</ref><ref name="pmid1874739">{{cite journal | vauthors = Bai RL, Paull KD, Herald CL, Malspeis L, Pettit GR, Hamel E | title = 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 | journal = The Journal of Biological Chemistry | volume = 266 | issue = 24 | pages = 15882–9 | date = August 1991 | doi = 10.1016/S0021-9258(18)98491-7 | pmid = 1874739 | doi-access = free | title-link = doi }}</ref>

Eribulin is a mechanistically unique ],<ref name="pmid16020666">{{cite journal | vauthors = Jordan MA, Kamath K, Manna T, Okouneva T, Miller HP, Davis C, Littlefield BA, Wilson L | title = The primary antimitotic mechanism of action of the synthetic halichondrin E7389 is suppression of microtubule growth | journal = Molecular Cancer Therapeutics | volume = 4 | issue = 7 | pages = 1086–95 | date = July 2005 | pmid = 16020666 | doi = 10.1158/1535-7163.MCT-04-0345 | s2cid = 38459382 | doi-access = free | title-link = doi }}</ref><ref name="pmid18645010">{{cite journal | vauthors = Okouneva T, Azarenko O, Wilson L, Littlefield BA, Jordan MA | title = Inhibition of centromere dynamics by eribulin (E7389) during mitotic metaphase | journal = Molecular Cancer Therapeutics | volume = 7 | issue = 7 | pages = 2003–11 | date = July 2008 | pmid = 18645010 | pmc = 2562299 | doi = 10.1158/1535-7163.MCT-08-0095 }}</ref> binding predominantly to a small number of high affinity sites at the plus ends of existing microtubules.<ref name="pmid20030375">{{cite journal | vauthors = Smith JA, Wilson L, Azarenko O, Zhu X, Lewis BM, Littlefield BA, Jordan MA | title = Eribulin binds at microtubule ends to a single site on tubulin to suppress dynamic instability | journal = Biochemistry | volume = 49 | issue = 6 | pages = 1331–7 | date = February 2010 | pmid = 20030375 | pmc = 2846717 | doi = 10.1021/bi901810u }}</ref><ref>{{cite journal | vauthors = Wilson L, Lopus M, Miller HP, Azarenko O, Riffle S, Smith JA, Jordan MA | title = Effects of eribulin on microtubule binding and dynamic instability are strengthened in the absence of the βIII tubulin isotype | journal = Biochemistry | volume = 54 | issue = 42 | pages = 6482–9 | date = October 2015 | pmid = 26435331 | doi = 10.1021/acs.biochem.5b00745 }}</ref>
Eribulin has both cytotoxic and non-cytotoxic mechanisms of action. Its cytotoxic effects are related to its antimitotic activities, wherein ] of cancer cells is induced following prolonged and irreversible mitotic blockade.<ref name="pmid15313917">{{cite journal | vauthors = Kuznetsov G, Towle MJ, Cheng H, Kawamura T, TenDyke K, Liu D, Kishi Y, Yu MJ, Littlefield BA | title = Induction of morphological and biochemical apoptosis following prolonged mitotic blockage by halichondrin B macrocyclic ketone analog E7389 | journal = Cancer Research | volume = 64 | issue = 16 | pages = 5760–6 | date = August 2004 | pmid = 15313917 | doi = 10.1158/0008-5472.CAN-04-1169 | s2cid = 30919443 | doi-access = free | title-link = doi }}</ref><ref name="pmid21127197">{{cite journal | vauthors = Towle MJ, Salvato KA, Wels BF, Aalfs KK, Zheng W, Seletsky BM, Zhu X, Lewis BM, Kishi Y, Yu MJ, Littlefield BA | title = Eribulin induces irreversible mitotic blockade: implications of cell-based pharmacodynamics for in vivo efficacy under intermittent dosing conditions | journal = Cancer Research | volume = 71 | issue = 2 | pages = 496–505 | date = January 2011 | pmid = 21127197 | doi = 10.1158/0008-5472.CAN-10-1874 | doi-access = free | title-link = doi }}</ref> In addition to its cytotoxic, antimitotic-based mechanisms, preclinical studies in human breast cancer models have shown that eribulin also exerts complex effects on the biology of surviving cancer cells and residual tumors that appear unrelated to its antimitotic effects. These non-mitotic mechanisms include vascular remodeling that leads to increased tumor perfusion and mitigation of tumor ], phenotypic changes consistent with reversal of ] (EMT), and decreased capacity for migration and invasion leading to reduced metastatic capacity as measured in a preclinical experimental metastasis model.<ref name="pmid25060424">{{cite journal | vauthors = Funahashi Y, Okamoto K, Adachi Y, Semba T, Uesugi M, Ozawa Y, Tohyama O, Uehara T, Kimura T, Watanabe H, Asano M, Kawano S, Tizon X, McCracken PJ, Matsui J, Aoshima K, Nomoto K, Oda Y | title = Eribulin mesylate reduces tumor microenvironment abnormality by vascular remodeling in preclinical human breast cancer models | journal = Cancer Science | volume = 105 | issue = 10 | pages = 1334–42 | date = October 2014 | pmid = 25060424 | pmc = 4462349 | doi = 10.1111/cas.12488 }}</ref><ref name="pmid24569463">{{cite journal | vauthors = Yoshida T, Ozawa Y, Kimura T, Sato Y, Kuznetsov G, Xu S, Uesugi M, Agoulnik S, Taylor N, Funahashi Y, Matsui J | title = Eribulin mesilate suppresses experimental metastasis of breast cancer cells by reversing phenotype from epithelial-mesenchymal transition (EMT) to mesenchymal-epithelial transition (MET) states | journal = British Journal of Cancer | volume = 110 | issue = 6 | pages = 1497–505 | date = March 2014 | pmid = 24569463 | pmc = 3960630 | doi = 10.1038/bjc.2014.80 }}</ref> In other studies, eribulin treatment of ] and ] cells leads to increased expression of ] and ] differentiation antigens, respectively.<ref name="pmid27069131">{{cite journal | vauthors = Kawano S, Asano M, Adachi Y, Matsui J | title = Antimitotic and Non-mitotic Effects of Eribulin Mesilate in Soft Tissue Sarcoma | journal = Anticancer Research | volume = 36 | issue = 4 | pages = 1553–61 | date = April 2016 | pmid = 27069131 }}</ref> Taxane-resistant cancers are often unresponsive to eribulin. A recent study found that this resistance is due to expression of multidrug resistance protein 1 (MDR1).<ref name="pmid25378644">{{cite journal | vauthors = Laughney AM, Kim E, Sprachman MM, Miller MA, Kohler RH, Yang KS, Orth JD, Mitchison TJ, Weissleder R | title = Single-cell pharmacokinetic imaging reveals a therapeutic strategy to overcome drug resistance to the microtubule inhibitor eribulin | journal = Science Translational Medicine | volume = 6 | issue = 261 | pages = 261ra152 | date = November 2014 | pmid = 25378644 | pmc = 4330962 | doi = 10.1126/scitranslmed.3009318 }}</ref> Fluorescently labeled eribulin has been used to study the ] and ] at single cell level ''in vivo''.<ref name="pmid25378644"/>

The synthesis of eribulin was first published<ref>{{cite journal | vauthors = Seletsky BM, Wang Y, Hawkins LD, Palme MH, Habgood GJ, DiPietro LV, Towle MJ, Salvato KA, Wels BF, Aalfs KK, Kishi Y, Littlefield BA, Yu MJ | title = Structurally simplified macrolactone analogues of halichondrin B | journal = Bioorganic & Medicinal Chemistry Letters | volume = 14 | issue = 22 | pages = 5547–50 | date = November 2004 | pmid = 15482921 | doi = 10.1016/j.bmcl.2004.08.068 }}</ref> in 2001; a new synthetic route to the drug was published in 2009.<ref name="pmid19807076">{{cite journal | vauthors = Kim DS, Dong CG, Kim JT, Guo H, Huang J, Tiseni PS, Kishi Y | title = New syntheses of E7389 C14-C35 and halichondrin C14-C38 building blocks: double-inversion approach | journal = Journal of the American Chemical Society | volume = 131 | issue = 43 | pages = 15636–41 | date = November 2009 | pmid = 19807076 | doi = 10.1021/ja9058475 }}</ref>

==Research==
Eribulin is being investigated for use in a variety of solid tumors, including ], ], ], ], ], ], ], ]s, and various ]s.<ref>{{cite web | title = 184 Studies found for: eribulin OR E7389 | url = http://www.clinicaltrials.gov/ct2/results?term=eribulin+OR+E7389 | work = ClinicalTrials.gov | publisher = U.S. National Library of Medicine}}</ref>

Two eribulin based products are in the research and development phase; a liposomal formulation and antibody drug combination therapy, both are for the treatment of solid tumors. The liposomal formulation of eribulin, E7389 liposomal, is in Phase I clinical trials.<ref>{{ClinicalTrialsGov|NCT03207672|Study of E7389 Liposomal Formulation in Subjects With Solid Tumor}}</ref> Preliminary ''in vivo'' experiments show a decrease in C(max) and a longer half-life with the liposomal formulation.<ref name=pmid23313921>{{cite journal | vauthors = Yu Y, Desjardins C, Saxton P, Lai G, Schuck E, Wong YN | title = Characterization of the pharmacokinetics of a liposomal formulation of eribulin mesylate (E7389) in mice | journal = International Journal of Pharmaceutics | volume = 443 | issue = 1–2 | pages = 9–16 | date = February 2013 | pmid = 23313921 | doi = 10.1016/j.ijpharm.2013.01.010 }}</ref> The drug antibody eribulin combination therapy is a joint venture between Eisai and Merck. The clinical trials combine eribulin and ], a ], for the treatment of breast cancer and other advanced cancers.<ref>{{ClinicalTrialsGov|NCT03222856|Ph II Study of Pembrolizumab & Eribulin in Patients With HR+/HER2- MBC Previously Treated With Anthracyclines & Taxanes (KELLY)}}</ref>

== References ==
{{reflist}}

{{Intracellular chemotherapeutic agents}}
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