You are using an unsupported browser. Please upgrade your browser to a newer version to get the best experience on DrugBank.
Identification
NameEribulin
Accession NumberDB08871
TypeSmall Molecule
GroupsApproved, Investigational
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. [PMID: 23010853]

Structure
Thumb
Synonyms
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
eribulin mesylate
Halaven
L01XX41
External Identifiers
  • E7389
  • ER-086526
  • NSC-707389
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Halaveninjection.5 mg/mLintravenousEisai Inc.2010-11-15Not applicableUs
Halavensolution0.5 mgintravenousEisai Limited2012-03-19Not applicableCanada
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixturesNot Available
SaltsNot Available
Categories
UNIILR24G6354G
CAS number253128-41-5
WeightAverage: 729.8966
Monoisotopic: 729.408811735
Chemical FormulaC40H59NO11
InChI KeyInChIKey=UFNVPOGXISZXJD-WVMZDRIUSA-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,29S,31R,32S,33R,35R,36S)-20-[(2S)-3-amino-2-hydroxypropyl]-21-methoxy-14-methyl-8,15-dimethylidene-2,19,30,34,37,39,40,41-octaoxanonacyclo[24.9.2.1³,³².1³,³³.1⁶,⁹.1¹²,¹⁶.0¹⁸,²².0²⁹,³⁶.0³¹,³⁵]hentetracontan-24-one
SMILES
[H][C@@]12O[C@@]3([H])CCC4CC(=O)C[[email protected]]5[[email protected]](C[[email protected]]6O[[email protected]](C[C@@H](C)C6=C)CC[C@@H]6O[[email protected]](CC6=C)CC[C@@]67C[C@@H](O[[email protected]]1[C@@H](O6)[C@@]3([H])O4)[C@@H]2O7)O[[email protected]](C[[email protected]](O)CN)[C@@H]5OC
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as furopyrans. These are organic polycyclic compounds containing a furan ring fused to a pyran ring. Furan is a five-membered aromatic ring with four carbon atoms and one oxygen atom. Pyran a six-membered heterocyclic, non-aromatic ring, made up of five carbon atoms and one oxygen atom and containing two double bonds.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassFuropyrans
Sub ClassNot Available
Direct ParentFuropyrans
Alternative Parents
Substituents
  • Furopyran
  • Furofuran
  • Dioxepane
  • 1,4-dioxepane
  • 1,3-dioxepane
  • Pyran
  • Oxane
  • Monosaccharide
  • Oxolane
  • Furan
  • Cyclic ketone
  • Secondary alcohol
  • Ketone
  • 1,2-aminoalcohol
  • Oxacycle
  • Ether
  • Dialkyl ether
  • Acetal
  • Hydrocarbon derivative
  • Primary amine
  • Organooxygen compound
  • Organonitrogen compound
  • Primary aliphatic amine
  • Carbonyl group
  • Amine
  • Alcohol
  • Aliphatic heteropolycyclic compound
Molecular FrameworkAliphatic heteropolycyclic compounds
External DescriptorsNot Available
Pharmacology
IndicationFor the treatment of patients with metastatic breast cancer who have previously received at least two chemotherapeutic regimens for the treatment of metastatic cancer.
PharmacodynamicsLinear
Mechanism of actionEribulin 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]
Related Articles
AbsorptionNot Available
Volume of distribution

43 L/m2 to 114 L/m2

Protein binding49 to 65%.
Metabolism

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

Route of eliminationEribulin is eliminated primarily in feces unchanged.
Half lifeabout 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]

ToxicityPeripheral 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 organismsNot Available
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
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 )
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage forms
FormRouteStrength
Injectionintravenous.5 mg/mL
Solutionintravenous0.5 mg
PricesNot Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US6214865 No2003-07-202023-07-20Us
US6469182 No1999-06-162019-06-16Us
US7470720 No1999-06-162019-06-16Us
US8097648 No2001-01-222021-01-22Us
Properties
StateLiquid
Experimental PropertiesNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.0798 mg/mLALOGPS
logP1.26ALOGPS
logP2.31ChemAxon
logS-4ALOGPS
pKa (Strongest Acidic)14.81ChemAxon
pKa (Strongest Basic)9.39ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count12ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area146.39 Å2ChemAxon
Rotatable Bond Count4ChemAxon
Refractivity186 m3·mol-1ChemAxon
Polarizability77.52 Å3ChemAxon
Number of Rings9ChemAxon
Bioavailability0ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis ReferenceNot Available
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 ]
External Links
ATC CodesL01XX41
AHFS Codes
  • 10:00
PDB EntriesNot Available
FDA labelDownload (194 KB)
MSDSDownload (120 KB)
Interactions
Drug Interactions
Drug
CitalopramEribulin may increase the QTc-prolonging activities of Citalopram.
ClozapineThe risk or severity of adverse effects can be increased when Eribulin is combined with Clozapine.
DofetilideEribulin may increase the QTc-prolonging activities of Dofetilide.
GoserelinEribulin may increase the QTc-prolonging activities of Goserelin.
LeuprolideEribulin may increase the QTc-prolonging activities of Leuprolide.
MetamizoleThe risk or severity of adverse effects can be increased when Metamizole is combined with Eribulin.
MifepristoneMifepristone may increase the QTc-prolonging activities of Eribulin.
Food InteractionsNot Available
Comments
comments powered by Disqus
Drug created on May 02, 2013 13:55 / Updated on June 26, 2016 01:53