Eribulin

Identification

Name
Eribulin
Accession Number
DB08871
Description

Eribulin is a microtubule inhibitor indicated for the treatment of patients with metastatic breast cancer who have previously received at least two chemotherapeutic regimens for the treatment of metastatic disease. Eribulin was isolated from the marine sponge Halichondria okadai. Eribulin is also being investigated for use in the treatment of advanced solid tumors 2.

Type
Small Molecule
Groups
Approved, Investigational
Structure
Thumb
Weight
Average: 729.908
Monoisotopic: 729.408811724
Chemical Formula
C40H59NO11
Synonyms
  • Eribulin
  • Eribulina
External IDs
  • ER-086526

Pharmacology

Indication

For the treatment of patients with metastatic breast cancer who have previously received at least two chemotherapeutic regimens for the treatment of metastatic cancer.

Associated Conditions
Contraindications & Blackbox Warnings
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Pharmacodynamics

Linear

Mechanism of action

Eribulin inhibits the growth phase of microtubules without affecting the shortening phase and sequesters tubulin into nonproductive aggregates. Eribulin exerts its effects via a tubulin-based antimitotic mechanism leading to G2/M cell-cycle block, disruption of mitotic spindles, and, ultimately, apoptotic cell death after prolonged mitotic blockage. [FDA]

TargetActionsOrganism
UApoptosis regulator Bcl-2Not AvailableHumans
UTubulin beta-1 chainNot AvailableHumans
Absorption
Not Available
Volume of distribution

43 L/m2 to 114 L/m2

Protein binding

49 to 65%.

Metabolism

There are no major human metabolites of eribulin, CYP3A4 negligibly metabolizes eribulin in vitro.

Route of elimination

Eribulin is eliminated primarily in feces unchanged.

Half-life

about 40 hours

Clearance

1.16 L/hr/m2 to 2.42 L/hr/m2 (dose range of 0.25 mg/m2 to 4.0 mg/m2). [FDA]

Adverse Effects
Learn about our commercial Adverse Effects data.
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Toxicity

Peripheral neuropathy was the most common toxicity leading to discontinuation of eribulin (5 percent). [Richard Pazdur, M.D., director of the FDA's Division of Oncology Drug Products.] Single doses of 0.75 mg/kg were lethal to rats and two doses of 0.075 mg/kg were lethal to dogs. The no-observed-adverse-effect level (NOAEL) in rats and dogs were 0.015 and 0.0045 mg/kg/day, respectively.

Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbataceptThe risk or severity of adverse effects can be increased when Abatacept is combined with Eribulin.
AbciximabThe risk or severity of bleeding can be increased when Abciximab is combined with Eribulin.
AcebutololThe risk or severity of QTc prolongation can be increased when Eribulin is combined with Acebutolol.
AcenocoumarolThe risk or severity of bleeding can be increased when Acenocoumarol is combined with Eribulin.
Acetylsalicylic acidThe risk or severity of bleeding can be increased when Acetylsalicylic acid is combined with Eribulin.
AcrivastineThe risk or severity of QTc prolongation can be increased when Eribulin is combined with Acrivastine.
AdalimumabThe risk or severity of adverse effects can be increased when Adalimumab is combined with Eribulin.
AdenosineThe risk or severity of QTc prolongation can be increased when Eribulin is combined with Adenosine.
Adenovirus type 7 vaccine liveThe risk or severity of infection can be increased when Adenovirus type 7 vaccine live is combined with Eribulin.
AjmalineThe risk or severity of QTc prolongation can be increased when Ajmaline is combined with Eribulin.
Additional Data Available
  • Extended Description
    Extended Description

    Extended description of the mechanism of action and particular properties of each drug interaction.

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  • Severity
    Severity

    A severity rating for each drug interaction, from minor to major.

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  • Evidence Level
    Evidence Level

    A rating for the strength of the evidence supporting each drug interaction.

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  • Action
    Action

    An effect category for each drug interaction. Know how this interaction affects the subject drug.

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Food Interactions
No interactions found.

Products

Product Ingredients
IngredientUNIICASInChI Key
Eribulin mesylateAV9U0660CW441045-17-6QAMYWGZHLCQOOJ-WRNBYXCMSA-N
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
HalavenInjection, solution0.44 mg/mlIntravenousEisai Europe Ltd2011-03-17Not applicableEU flag
HalavenInjection0.5 mg/1mLIntravenousEisai Inc.2010-11-15Not applicableUS flag
HalavenInjection, solution0.44 mg/mlIntravenousEisai Europe Ltd2011-03-17Not applicableEU flag
HalavenInjection0.5 mg/1mLIntravenousBSP Pharmaceuticals SpA2017-04-21Not applicableUS flag
HalavenInjection, solution0.44 mg/mlIntravenousEisai Europe Ltd2011-03-17Not applicableEU flag
HalavenSolution0.5 mgIntravenousEisai Limited2012-03-19Not applicableCanada flag
HalavenInjection, solution0.44 mg/mlIntravenousEisai Europe Ltd2011-03-17Not applicableEU flag
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Categories

ATC Codes
L01XX41 — Eribulin
Drug Categories
Classification
Not classified

Chemical Identifiers

UNII
LR24G6354G
CAS number
253128-41-5
InChI Key
UFNVPOGXISZXJD-JBQZKEIOSA-N
InChI
InChI=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
IUPAC Name
(1S,3S,6S,9S,12S,14R,16R,18S,20R,21R,22S,26R,29S,31R,32S,33S,35R,36S)-20-[(2S)-3-amino-2-hydroxypropyl]-21-methoxy-14-methyl-8,15-dimethylidene-2,19,30,34,37,39,40,41-octaoxanonacyclo[24.9.2.1^{3,32}.1^{3,33}.1^{6,9}.1^{12,16}.0^{18,22}.0^{29,36}.0^{31,35}]hentetracontan-24-one
SMILES

References

General References
  1. Shablak A: Eribulin for advanced breast cancer: a drug evaluation. J Breast Cancer. 2013 Mar;16(1):12-5. doi: 10.4048/jbc.2013.16.1.12. Epub 2013 Mar 31. [PubMed:23593076]
  2. Devriese LA, Witteveen PO, Marchetti S, Mergui-Roelvink M, Reyderman L, Wanders J, Jenner A, Edwards G, Beijnen JH, Voest EE, Schellens JH: Pharmacokinetics of eribulin mesylate in patients with solid tumors and hepatic impairment. Cancer Chemother Pharmacol. 2012 Dec;70(6):823-32. doi: 10.1007/s00280-012-1976-x. Epub 2012 Sep 26. [PubMed:23010853]
  3. Nieder C, Aandahl G, Dalhaug A: A case of brain metastases from breast cancer treated with whole-brain radiotherapy and eribulin mesylate. Case Rep Oncol Med. 2012;2012:537183. doi: 10.1155/2012/537183. Epub 2012 Aug 16. [PubMed:22953094]
  4. Jordan MA, Kamath K, Manna T, Okouneva T, Miller HP, Davis C, Littlefield BA, Wilson L: The primary antimitotic mechanism of action of the synthetic halichondrin E7389 is suppression of microtubule growth. Mol Cancer Ther. 2005 Jul;4(7):1086-95. [PubMed:16020666]
KEGG Drug
D08914
PubChem Compound
73425383
PubChem Substance
175427126
ChemSpider
24721813
RxNav
1045453
ChEBI
63587
ChEMBL
CHEMBL1683590
ZINC
ZINC000169344691
PDBe Ligand
6K9
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
PDRhealth
PDRhealth Drug Page
Wikipedia
Eribulin
AHFS Codes
  • 10:00.00 — Antineoplastic Agents
PDB Entries
5jh7
FDA label
Download (194 KB)
MSDS
Download (120 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4CompletedTreatmentBreast Cancer / Neoplasms, Breast1
4CompletedTreatmentNeoplasms, Breast1
4Unknown StatusHealth Services ResearchAdverse Drug Events / Metastatic Breast Cancer / Neurologic toxicity / Therapeutic Agent Toxicity1
3Active Not RecruitingTreatmentBreast Cancer1
3Active Not RecruitingTreatmentHER2 Positive Breast Cancers / Neoplasms, Metastatic1
3Active Not RecruitingTreatmentHER2-positive Locally Advanced or Metastatic Breast Cancer1
3Active Not RecruitingTreatmentMetastatic Breast Cancer1
3Active Not RecruitingTreatmentMetastatic Triple Negative Breast Cancer1
3CompletedTreatmentBreast Cancer1
3CompletedTreatmentBreast Cancer / Cancer of the Breast / HER2 Negative Breast Cancer / HER2-Negative Breast Cancer / Triple Negative Breast Cancer (TNBC) / Tumors, Breast1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
Injection
InjectionIntravenous0.5 mg/1mL
Injection, solution1 mg/2mL
Injection, solutionIntravenous0.44 mg/ml
Injection, solutionIntravenous; Parenteral0.44 MG/ML
SolutionIntravenous0.5 mg
Solution
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US8097648No2012-01-172021-01-22US flag
US6469182No2002-10-222019-06-16US flag
US7470720No2008-12-302019-06-16US flag
US6214865No2001-04-102023-07-20US flag
USRE46965No2018-07-242027-01-08US flag
Additional Data Available
  • Filed On
    Filed On

    The date on which a patent was filed with the relevant government.

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Properties

State
Liquid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0798 mg/mLALOGPS
logP1.26ALOGPS
logP2.31ChemAxon
logS-4ALOGPS
pKa (Strongest Acidic)14.82ChemAxon
pKa (Strongest Basic)9.56ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count12ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area146.39 Å2ChemAxon
Rotatable Bond Count4ChemAxon
Refractivity186 m3·mol-1ChemAxon
Polarizability82.15 Å3ChemAxon
Number of Rings9ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.6417
Blood Brain Barrier-0.7893
Caco-2 permeable-0.646
P-glycoprotein substrateSubstrate0.8239
P-glycoprotein inhibitor IInhibitor0.5443
P-glycoprotein inhibitor IINon-inhibitor0.6565
Renal organic cation transporterNon-inhibitor0.7978
CYP450 2C9 substrateNon-substrate0.9256
CYP450 2D6 substrateNon-substrate0.7965
CYP450 3A4 substrateSubstrate0.6412
CYP450 1A2 substrateNon-inhibitor0.8332
CYP450 2C9 inhibitorNon-inhibitor0.8636
CYP450 2D6 inhibitorNon-inhibitor0.8939
CYP450 2C19 inhibitorNon-inhibitor0.7838
CYP450 3A4 inhibitorNon-inhibitor0.7094
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9246
Ames testNon AMES toxic0.7043
CarcinogenicityNon-carcinogens0.9719
BiodegradationNot ready biodegradable0.9841
Rat acute toxicity2.9429 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9408
hERG inhibition (predictor II)Inhibitor0.5065
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
Not Available

Targets

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Ubiquitin protein ligase binding
Specific Function
Suppresses apoptosis in a variety of cell systems including factor-dependent lymphohematopoietic and neural cells. Regulates cell death by controlling the mitochondrial membrane permeability. Appea...
Gene Name
BCL2
Uniprot ID
P10415
Uniprot Name
Apoptosis regulator Bcl-2
Molecular Weight
26265.66 Da
References
  1. Kuznetsov G, Towle MJ, Cheng H, Kawamura T, TenDyke K, Liu D, Kishi Y, Yu MJ, Littlefield BA: Induction of morphological and biochemical apoptosis following prolonged mitotic blockage by halichondrin B macrocyclic ketone analog E7389. Cancer Res. 2004 Aug 15;64(16):5760-6. [PubMed:15313917]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Structural constituent of cytoskeleton
Specific Function
Tubulin is the major constituent of microtubules. It binds two moles of GTP, one at an exchangeable site on the beta chain and one at a non-exchangeable site on the alpha chain (By similarity).
Gene Name
TUBB1
Uniprot ID
Q9H4B7
Uniprot Name
Tubulin beta-1 chain
Molecular Weight
50326.56 Da
References
  1. Dabydeen DA, Burnett JC, Bai R, Verdier-Pinard P, Hickford SJ, Pettit GR, Blunt JW, Munro MH, Gussio R, Hamel E: Comparison of the activities of the truncated halichondrin B analog NSC 707389 (E7389) with those of the parent compound and a proposed binding site on tubulin. Mol Pharmacol. 2006 Dec;70(6):1866-75. Epub 2006 Aug 29. [PubMed:16940412]

Drug created on May 02, 2013 13:55 / Updated on October 21, 2020 01:55

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