Eribulin

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Pharmaceutical drug

title: "Eribulin" type: doc version: 1 created: 2026-02-28 author: "Wikipedia contributors" status: active scope: public tags: ["antineoplastic-drugs", "macrocycles", "orphan-drugs", "tetrahydropyrans", "tetrahydrofurans", "methoxy-compounds", "amines"] description: "Pharmaceutical drug" topic_path: "general/antineoplastic-drugs" source: "https://en.wikipedia.org/wiki/Eribulin" license: "CC BY-SA 4.0" wikipedia_page_id: 0 wikipedia_revision_id: 0

::summary Pharmaceutical drug ::

::data[format=table title="Infobox drug"]

FieldValue
Verifiedfieldschanged
verifiedrevid461094948
imageEribulin.svg
image_classskin-invert-image
width300
USANeribulin mesylate
JANeribulin mesilate
tradenameHalaven, Mevlyq
Drugs.com
MedlinePlusa611007
DailyMedIDEribulin
pregnancy_AUD
pregnancy_AU_comment
routes_of_administrationIntravenous
classAntineoplastic
ATC_prefixL01
ATC_suffixXX41
legal_AUS4
legal_BR
legal_CARx-only
legal_CA_comment
legal_DE
legal_NZ
legal_UKPOM
legal_UK_comment
legal_USRx-only
legal_US_comment
legal_EURx-only
legal_EU_comment
legal_UN
legal_statusRx-only
CAS_number_Ref
CAS_number253128-41-5
PubChem11354606
DrugBank_Ref
DrugBankDB08871
ChemSpiderID_Ref
ChemSpiderID24721813
UNII_Ref
UNIILR24G6354G
KEGGD08914
ChEBI63587
ChEMBL_Ref
ChEMBL1683590
synonymsE7389, ER-086526, NSC-707389
IUPAC_name2-(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
C40
SMILESCC1CC2CCC3C(=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
StdInChI_Ref
StdInChI1S/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
StdInChIKey_Ref
StdInChIKeyUFNVPOGXISZXJD-JBQZKEIOSA-N
::

| Verifiedfields = changed | verifiedrevid = 461094948 | image = Eribulin.svg | image_class = skin-invert-image | width = 300 | alt = | caption = | USAN = eribulin mesylate | JAN = eribulin mesilate

| pronounce = | tradename = Halaven, Mevlyq | Drugs.com = | MedlinePlus = a611007 | DailyMedID = Eribulin | pregnancy_AU = D | pregnancy_AU_comment = | pregnancy_category = | routes_of_administration = Intravenous | class = Antineoplastic | ATC_prefix = L01 | ATC_suffix = XX41 | ATC_supplemental =

| legal_AU = S4 | legal_AU_comment = | legal_BR = | legal_BR_comment = | legal_CA = Rx-only | legal_CA_comment = | legal_DE = | legal_DE_comment = | legal_NZ = | legal_NZ_comment = | legal_UK = POM | legal_UK_comment = | legal_US = Rx-only | legal_US_comment = | legal_EU = Rx-only | legal_EU_comment = | legal_UN = | legal_UN_comment = | legal_status = Rx-only

| bioavailability = | protein_bound = | metabolism = | metabolites = | onset = | elimination_half-life = | duration_of_action = | excretion =

| CAS_number_Ref = | CAS_number = 253128-41-5 | CAS_supplemental = | PubChem = 11354606 | IUPHAR_ligand = | DrugBank_Ref = | DrugBank = DB08871 | ChemSpiderID_Ref = | ChemSpiderID = 24721813 | UNII_Ref = | UNII = LR24G6354G | KEGG_Ref = | KEGG = D08914 | ChEBI_Ref = | ChEBI = 63587 | ChEMBL_Ref = | ChEMBL = 1683590 | NIAID_ChemDB = | PDB_ligand = | synonyms = E7389, ER-086526, NSC-707389

| 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 | 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 | StdInChI_Ref = | 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 = | 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 anti-cancer medication used to treat breast cancer and liposarcoma.

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). Eribulin may also cause low levels of infection-fighting white blood cells (neutropenia) or decreased levels of potassium or calcium.

Eribulin was approved for medical use in the United States in November 2010, the European Union in March 2011, and Canada in December 2011. It is available as a generic medication.

Medical uses

Eribulin is indicated for the treatment of people with locally advanced or metastatic breast cancer, and for the treatment of adults with unresectable liposarcoma.

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.

Structure and mechanism

Eribulin is a fully synthetic macrocyclic ketone analog of the marine natural product halichondrin B, the parent molecule being a naturally occurring, potent mitotic inhibitor with a unique mechanism of action. The parent molecule was originally found in the sponge Halichondria okadai.

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 has both cytotoxic and non-cytotoxic mechanisms of action. Its cytotoxic effects are related to its antimitotic activities, wherein apoptosis of cancer cells is induced following prolonged and irreversible mitotic blockade. 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 hypoxia, phenotypic changes consistent with reversal of epithelial-mesenchymal transition (EMT), and decreased capacity for migration and invasion leading to reduced metastatic capacity as measured in a preclinical experimental metastasis model. In other studies, eribulin treatment of leiomyosarcoma and liposarcoma cells leads to increased expression of smooth muscle and adipocyte differentiation antigens, respectively. 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). Fluorescently labeled eribulin has been used to study the pharmacokinetics and pharmacodynamics at single cell level in vivo.

The synthesis of eribulin was first published in 2001; a new synthetic route to the drug was published in 2009.

Research

Eribulin is being investigated for use in a variety of solid tumors, including breast cancer, non-small cell lung cancer, prostate cancer, brain cancer, cervical cancer, urothelial cancer, melanoma, solitary fibrous tumors, and various sarcomas.

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. Preliminary in vivo experiments show a decrease in C(max) and a longer half-life with the liposomal formulation. The drug antibody eribulin combination therapy is a joint venture between Eisai and Merck. The clinical trials combine eribulin and pembrolizumab, a PD-1 inhibitor, for the treatment of breast cancer and other advanced cancers.

References

References

  1. (22 October 2019). "Eribulin (Halaven) Use During Pregnancy".
  2. (16 January 2023). "Halaven 0.44 mg/ml solution for injection".
  3. (17 March 2011). "Halaven EPAR".
  4. (9 February 2024). "Mevlyq EPAR".
  5. (13 February 2024). "Mevlyq product information".
  6. (19 July 2011). "Eisai Announces Japan Launch Of Anticancer Agent Halaven". Eisai Co., Ltd..
  7. (17 July 2019). "Anticancer Agent Halaven Approved For Treatment Of Locally Advanced Or Metastatic Breast Cancer In China". Eisai Co., Ltd..
  8. (22 December 2017). "Halaven- eribulin mesylate injection".
  9. "Drug Approval Package: Halaven (erbulin mesylate) NDA 201532".
  10. (22 October 2009). "Halaven Product information".
  11. (9 March 2015). "Halaven for Metastatic Breast Cancer".
  12. "Eisai Announces Canadian Approval of its Anticancer Agent Halaven".
  13. (15 November 2010). "FDA approves new treatment option for late-stage breast cancer". U.S. [[Food and Drug Administration]] (FDA).
  14. (28 January 2016). "Eribulin".
  15. [http://www.hc-sc.gc.ca/dhp-mps/prodpharma/sbd-smd/drug-med/nd_ad_2012_halaven_141946-eng.php Notice of Decision for Halaven]{{dead link. (September 2017)
  16. (9 March 2015). "Halaven for Metastatic Breast Cancer".
  17. "Eisai Announces Canadian Approval of its Anticancer Agent Halaven".
  18. (May 2025). "FDA approves first drug to show survival benefit in liposarcoma".
  19. (29 January 2016). "U.S. FDA Approves Eisai's Anticancer Agent Halaven For The Treatment Of Advanced Liposarcoma". Eisai Co., Ltd..
  20. (5 June 2015). "Eribulin (Halaven)".
  21. (February 2001). "In vitro and in vivo anticancer activities of synthetic macrocyclic ketone analogues of halichondrin B". Cancer Research.
  22. (November 2017). "Anticancer agents from natural products". Taylor & Francis.
  23. (1 January 1986). "Halichondrins - antitumor polyether macrolides from a marine sponge". Pure and Applied Chemistry.
  24. (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". The Journal of Biological Chemistry.
  25. (July 2005). "The primary antimitotic mechanism of action of the synthetic halichondrin E7389 is suppression of microtubule growth". Molecular Cancer Therapeutics.
  26. (July 2008). "Inhibition of centromere dynamics by eribulin (E7389) during mitotic metaphase". Molecular Cancer Therapeutics.
  27. (February 2010). "Eribulin binds at microtubule ends to a single site on tubulin to suppress dynamic instability". Biochemistry.
  28. (October 2015). "Effects of eribulin on microtubule binding and dynamic instability are strengthened in the absence of the βIII tubulin isotype". Biochemistry.
  29. (August 2004). "Induction of morphological and biochemical apoptosis following prolonged mitotic blockage by halichondrin B macrocyclic ketone analog E7389". Cancer Research.
  30. (January 2011). "Eribulin induces irreversible mitotic blockade: implications of cell-based pharmacodynamics for in vivo efficacy under intermittent dosing conditions". Cancer Research.
  31. (October 2014). "Eribulin mesylate reduces tumor microenvironment abnormality by vascular remodeling in preclinical human breast cancer models". Cancer Science.
  32. (March 2014). "Eribulin mesilate suppresses experimental metastasis of breast cancer cells by reversing phenotype from epithelial-mesenchymal transition (EMT) to mesenchymal-epithelial transition (MET) states". British Journal of Cancer.
  33. (April 2016). "Antimitotic and Non-mitotic Effects of Eribulin Mesilate in Soft Tissue Sarcoma". Anticancer Research.
  34. (November 2014). "Single-cell pharmacokinetic imaging reveals a therapeutic strategy to overcome drug resistance to the microtubule inhibitor eribulin". Science Translational Medicine.
  35. (November 2004). "Structurally simplified macrolactone analogues of halichondrin B". Bioorganic & Medicinal Chemistry Letters.
  36. (November 2009). "New syntheses of E7389 C14-C35 and halichondrin C14-C38 building blocks: double-inversion approach". Journal of the American Chemical Society.
  37. "184 Studies found for: eribulin OR E7389". U.S. National Library of Medicine.
  38. {{ClinicalTrialsGov. NCT03207672. Study of E7389 Liposomal Formulation in Subjects With Solid Tumor
  39. (February 2013). "Characterization of the pharmacokinetics of a liposomal formulation of eribulin mesylate (E7389) in mice". International Journal of Pharmaceutics.
  40. {{ClinicalTrialsGov. NCT03222856. Ph II Study of Pembrolizumab & Eribulin in Patients With HR+/HER2- MBC Previously Treated With Anthracyclines & Taxanes (KELLY)

::callout[type=info title="Wikipedia Source"] This article was imported from Wikipedia and is available under the Creative Commons Attribution-ShareAlike 4.0 License. Content has been adapted to SurfDoc format. Original contributors can be found on the article history page. ::

antineoplastic-drugsmacrocyclesorphan-drugstetrahydropyranstetrahydrofuransmethoxy-compoundsamines