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Identification
NameEribulin
Accession NumberDB08871
TypeSmall Molecule
GroupsApproved, Investigational
DescriptionEribulin 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
HalavenSolution0.5 mgIntravenousEisai Limited2012-03-19Not applicableCanada
HalavenInjection, solution0.44 mg/mlIntravenousEisai Europe Ltd2011-03-17Not applicableEu
HalavenInjection, solution0.44 mg/mlIntravenousEisai Europe Ltd2011-03-17Not applicableEu
HalavenInjection.5 mg/mLIntravenousEisai Inc.2010-11-15Not applicableUs
HalavenInjection, solution0.44 mg/mlIntravenousEisai Europe Ltd2011-03-17Not applicableEu
HalavenInjection, solution0.44 mg/mlIntravenousEisai Europe Ltd2011-03-17Not applicableEu
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 KeyUFNVPOGXISZXJD-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
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.
Structured Indications
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
Interactions
Drug Interactions
DrugInteractionDrug group
AcetyldigitoxinAcetyldigitoxin may decrease the cardiotoxic activities of Eribulin.Approved
AmiodaroneEribulin may increase the QTc-prolonging activities of Amiodarone.Approved, Investigational
AnagrelideEribulin may increase the QTc-prolonging activities of Anagrelide.Approved
AnvirzelAnvirzel may decrease the cardiotoxic activities of Eribulin.Investigational
Arsenic trioxideEribulin may increase the QTc-prolonging activities of Arsenic trioxide.Approved, Investigational
ArtemetherEribulin may increase the QTc-prolonging activities of Artemether.Approved
AsenapineEribulin may increase the QTc-prolonging activities of Asenapine.Approved
AzithromycinEribulin may increase the QTc-prolonging activities of Azithromycin.Approved
BcgThe therapeutic efficacy of Bcg can be decreased when used in combination with Eribulin.Investigational
BedaquilineEribulin may increase the QTc-prolonging activities of Bedaquiline.Approved
BevacizumabBevacizumab may increase the cardiotoxic activities of Eribulin.Approved, Investigational
CabazitaxelThe risk or severity of adverse effects can be increased when Cabazitaxel is combined with Eribulin.Approved
CeritinibEribulin may increase the QTc-prolonging activities of Ceritinib.Approved
ChloroquineEribulin may increase the QTc-prolonging activities of Chloroquine.Approved, Vet Approved
ChlorpromazineEribulin may increase the QTc-prolonging activities of Chlorpromazine.Approved, Vet Approved
CiprofloxacinEribulin may increase the QTc-prolonging activities of Ciprofloxacin.Approved, Investigational
CisaprideEribulin may increase the QTc-prolonging activities of Cisapride.Approved, Investigational, Withdrawn
CitalopramEribulin may increase the QTc-prolonging activities of Citalopram.Approved
ClarithromycinEribulin may increase the QTc-prolonging activities of Clarithromycin.Approved
ClozapineThe risk or severity of adverse effects can be increased when Eribulin is combined with Clozapine.Approved
CrizotinibEribulin may increase the QTc-prolonging activities of Crizotinib.Approved
CyclophosphamideCyclophosphamide may increase the cardiotoxic activities of Eribulin.Approved, Investigational
DeslanosideDeslanoside may decrease the cardiotoxic activities of Eribulin.Approved
DigitoxinDigitoxin may decrease the cardiotoxic activities of Eribulin.Approved
DigoxinDigoxin may decrease the cardiotoxic activities of Eribulin.Approved
DisopyramideEribulin may increase the QTc-prolonging activities of Disopyramide.Approved
DocetaxelThe risk or severity of adverse effects can be increased when Docetaxel is combined with Eribulin.Approved, Investigational
DofetilideEribulin may increase the QTc-prolonging activities of Dofetilide.Approved
DolasetronEribulin may increase the QTc-prolonging activities of Dolasetron.Approved
DomperidoneEribulin may increase the QTc-prolonging activities of Domperidone.Approved, Investigational, Vet Approved
DronedaroneEribulin may increase the QTc-prolonging activities of Dronedarone.Approved
DroperidolEribulin may increase the QTc-prolonging activities of Droperidol.Approved, Vet Approved
EliglustatEribulin may increase the QTc-prolonging activities of Eliglustat.Approved
ErythromycinEribulin may increase the QTc-prolonging activities of Erythromycin.Approved, Vet Approved
EscitalopramEribulin may increase the QTc-prolonging activities of Escitalopram.Approved, Investigational
FlecainideEribulin may increase the QTc-prolonging activities of Flecainide.Approved, Withdrawn
FluoxetineEribulin may increase the QTc-prolonging activities of Fluoxetine.Approved, Vet Approved
FlupentixolEribulin may increase the QTc-prolonging activities of Flupentixol.Approved, Withdrawn
Gadobenic acidEribulin may increase the QTc-prolonging activities of Gadobenic acid.Approved
GemifloxacinEribulin may increase the QTc-prolonging activities of Gemifloxacin.Approved, Investigational
GoserelinEribulin may increase the QTc-prolonging activities of Goserelin.Approved
GranisetronEribulin may increase the QTc-prolonging activities of Granisetron.Approved, Investigational
HaloperidolEribulin may increase the QTc-prolonging activities of Haloperidol.Approved
IbutilideEribulin may increase the QTc-prolonging activities of Ibutilide.Approved
IloperidoneEribulin may increase the QTc-prolonging activities of Iloperidone.Approved
LenvatinibEribulin may increase the QTc-prolonging activities of Lenvatinib.Approved
LeuprolideEribulin may increase the QTc-prolonging activities of Leuprolide.Approved, Investigational
LevofloxacinEribulin may increase the QTc-prolonging activities of Levofloxacin.Approved, Investigational
LopinavirEribulin may increase the QTc-prolonging activities of Lopinavir.Approved
LumefantrineEribulin may increase the QTc-prolonging activities of Lumefantrine.Approved
MetamizoleThe risk or severity of adverse effects can be increased when Metamizole is combined with Eribulin.Withdrawn
MethadoneEribulin may increase the QTc-prolonging activities of Methadone.Approved
MifepristoneMifepristone may increase the QTc-prolonging activities of Eribulin.Approved, Investigational
MoxifloxacinEribulin may increase the QTc-prolonging activities of Moxifloxacin.Approved, Investigational
NilotinibEribulin may increase the QTc-prolonging activities of Nilotinib.Approved, Investigational
OfloxacinEribulin may increase the QTc-prolonging activities of Ofloxacin.Approved
OndansetronEribulin may increase the QTc-prolonging activities of Ondansetron.Approved
OuabainOuabain may decrease the cardiotoxic activities of Eribulin.Approved
PaclitaxelThe risk or severity of adverse effects can be increased when Paclitaxel is combined with Eribulin.Approved, Vet Approved
PaliperidoneEribulin may increase the QTc-prolonging activities of Paliperidone.Approved
PanobinostatEribulin may increase the QTc-prolonging activities of Panobinostat.Approved, Investigational
PazopanibEribulin may increase the QTc-prolonging activities of Pazopanib.Approved
PentamidineEribulin may increase the QTc-prolonging activities of Pentamidine.Approved
PerflutrenEribulin may increase the QTc-prolonging activities of Perflutren.Approved
PimozideEribulin may increase the QTc-prolonging activities of Pimozide.Approved
PrimaquineEribulin may increase the QTc-prolonging activities of Primaquine.Approved
ProcainamideEribulin may increase the QTc-prolonging activities of Procainamide.Approved
PromazineEribulin may increase the QTc-prolonging activities of Promazine.Approved, Vet Approved
PropafenoneEribulin may increase the QTc-prolonging activities of Propafenone.Approved
QuetiapineEribulin may increase the QTc-prolonging activities of Quetiapine.Approved
QuinidineEribulin may increase the QTc-prolonging activities of Quinidine.Approved
QuinineEribulin may increase the QTc-prolonging activities of Quinine.Approved
SaquinavirEribulin may increase the QTc-prolonging activities of Saquinavir.Approved, Investigational
SotalolEribulin may increase the QTc-prolonging activities of Sotalol.Approved
SulfisoxazoleEribulin may increase the QTc-prolonging activities of Sulfisoxazole.Approved, Vet Approved
TelavancinEribulin may increase the QTc-prolonging activities of Telavancin.Approved
TelithromycinEribulin may increase the QTc-prolonging activities of Telithromycin.Approved
TetrabenazineEribulin may increase the QTc-prolonging activities of Tetrabenazine.Approved
ThioridazineEribulin may increase the QTc-prolonging activities of Thioridazine.Approved
ToremifeneEribulin may increase the QTc-prolonging activities of Toremifene.Approved, Investigational
TrastuzumabTrastuzumab may increase the cardiotoxic activities of Eribulin.Approved, Investigational
VandetanibEribulin may increase the QTc-prolonging activities of Vandetanib.Approved
VemurafenibEribulin may increase the QTc-prolonging activities of Vemurafenib.Approved
ZiprasidoneEribulin may increase the QTc-prolonging activities of Ziprasidone.Approved
ZuclopenthixolEribulin may increase the QTc-prolonging activities of Zuclopenthixol.Approved, Investigational
Food InteractionsNot 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)
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
Injection, solutionIntravenous0.44 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
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
Comments
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Drug created on May 02, 2013 13:55 / Updated on December 07, 2016 02:39