eribulin Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |

Stem definitionDrug idCAS RN
antineoplastics; mitotic inhibitors, tubulin binders 4171 253128-41-5

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • eribulin mesylate
  • eribulin
  • halaven
  • E7389
  • eribulin mesilate
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. In addition, eribulin treatment of human breast cancer cells caused changes in morphology and gene expression as well as decreased migration and invasiveness in vitro. In mouse xenograft models of human breast cancer, eribulin treatment was associated with increased vascular perfusion and permeability in the tumor cores, resulting in reduced tumor hypoxia, and changes in the expression of genes in tumor specimens associated with a change in phenotype.
  • Molecular weight: 729.91
  • Formula: C40H59NO11
  • CLOGP: 1.24
  • LIPINSKI: 2
  • HAC: 12
  • HDO: 2
  • TPSA: 146.39
  • ALOGS: -3.96
  • ROTB: 4

  • Status: ONP

  • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

None

ADMET properties:

PropertyValueReference
Vd (Volume of distribution) 1.46 L/kg Lombardo F, Berellini G, Obach RS
CL (Clearance) 0.75 mL/min/kg Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma) 0.43 % Lombardo F, Berellini G, Obach RS
t_half (Half-life) 37.80 hours Lombardo F, Berellini G, Obach RS

Approvals:

DateAgencyCompanyOrphan
March 17, 2011 EMA
Nov. 15, 2010 FDA EISAI INC

FDA Adverse Event Reporting System (Female)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Neutropenia 1681.24 71.92 418 1994 21130 2334543
Febrile neutropenia 1341.40 71.92 307 2105 10575 2345098
Malignant neoplasm progression 1202.53 71.92 287 2125 11841 2343832
Leukopenia 562.66 71.92 152 2260 10044 2345629
Neuropathy peripheral 388.71 71.92 117 2295 11315 2344358
Interstitial lung disease 349.44 71.92 99 2313 7713 2347960
Pyrexia 253.20 71.92 131 2281 53577 2302096
Stomatitis 243.98 71.92 79 2333 9631 2346042
Mucosal inflammation 205.46 71.92 60 2352 5164 2350509
Anaemia 196.13 71.92 96 2316 34696 2320977
Metastases to bone 188.28 71.92 47 2365 2222 2353451
Disease progression 182.86 71.92 74 2338 17021 2338652
Pneumonia 175.38 71.92 100 2312 49196 2306477
Pseudocirrhosis 173.91 71.92 27 2385 86 2355587
Thrombocytopenia 168.16 71.92 72 2340 19059 2336614
Metastases to liver 148.10 71.92 41 2371 2900 2352773
Pleural effusion 122.83 71.92 50 2362 11618 2344055
Neutrophil count decreased 119.48 71.92 42 2370 6525 2349148
Haematotoxicity 116.15 71.92 28 2384 1139 2354534
Breast cancer metastatic 113.03 71.92 31 2381 2113 2353560
Sepsis 112.81 71.92 54 2358 18434 2337239
Fatigue 92.73 71.92 84 2328 84789 2270884
Vomiting 92.53 71.92 78 2334 71524 2284149
Decreased appetite 90.14 71.92 54 2358 28837 2326836
Breast cancer 84.08 71.92 36 2376 9459 2346214
Palmar-plantar erythrodysaesthesia syndrome 80.71 71.92 28 2384 4173 2351500
Alopecia 78.81 71.92 45 2367 21956 2333717
Pulmonary embolism 78.54 71.92 42 2370 18041 2337632
Lymphopenia 78.20 71.92 24 2388 2430 2353243
Metastases to skin 77.32 71.92 15 2397 212 2355461
Polyneuropathy 76.97 71.92 22 2390 1741 2353932
Asthenia 75.07 71.92 58 2354 46868 2308805
Nausea 74.73 71.92 85 2327 112104 2243569

FDA Adverse Event Reporting System (Male)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Febrile neutropenia 120.04 67.49 29 145 11071 1735536
Neutropenia 110.45 67.49 30 144 18230 1728377

Pharmacologic Action:

SourceCodeDescription
ATC L01XX41 ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
ANTINEOPLASTIC AGENTS
OTHER ANTINEOPLASTIC AGENTS
Other antineoplastic agents
FDA PE N0000175085 Microtubule Inhibition
FDA EPC N0000175592 Microtubule Inhibitor
CHEBI has role CHEBI:35610 antineoplastic agent

Drug Use (View source of the data)

DiseaseRelationSNOMED_IDDOID
Liposarcoma indication 254829001 DOID:3382
Metastatic Breast Carcinoma indication
Constipation contraindication 14760008 DOID:2089
Hypokalemia contraindication 43339004
Chronic heart failure contraindication 48447003
Bradycardia contraindication 48867003
Prolonged QT interval contraindication 111975006
Hypomagnesemia contraindication 190855004
Pregnancy, function contraindication 289908002
Thrombocytopenic disorder contraindication 302215000 DOID:1588
Peripheral nerve disease contraindication 302226006
Neutropenic disorder contraindication 303011007 DOID:1227
Congenital long QT syndrome contraindication 442917000

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 9.2 Basic

Orange Book patent data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRoutePatent numberPatent expiration datePatent use
1MG/2ML (0.5MG/ML) HALAVEN EISAI INC N201532 Nov. 15, 2010 RX SOLUTION INTRAVENOUS 8097648 Jan. 22, 2021 TREATMENT OF PATIENTS WITH METASTATIC BREAST CANCER

Orange Book exclusivity data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRouteExclusivity dateDescription
1MG/2ML (0.5MG/ML) HALAVEN EISAI INC N201532 Nov. 15, 2010 RX SOLUTION INTRAVENOUS Jan. 28, 2023 TREATMENT OF PATIENTS WITH UNRESECTABLE OR METASTATIC LIPOSARCOMA WHO HAVE RECEIVED A PRIOR ANTHRACYCLNE-CONTAINING REGIMEN

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])
Mechanism
action
Bioact sourceMoA source
Tubulin beta Tumour-associated antigen INHIBITOR IC50 8.23 IUPHAR SCIENTIFIC LITERATURE

External reference:

IDSource
4030296 VUID
N0000182254 NUI
C2608038 UMLSCUI
D08914 KEGG_DRUG
767582004 SNOMEDCT_US
1045453 RXNORM
013558 NDDF
4030302 VANDF
708166000 SNOMEDCT_US
d07716 MMSL
AV9U0660CW UNII
441045-17-6 SECONDARY_CAS_RN
8854 INN_ID
DB08871 DRUGBANK_ID
CHEBI:70710 CHEBI
CHEMBL1683544 ChEMBL_ID
CHEMBL1683590 ChEMBL_ID
11354606 PUBCHEM_CID
6813 IUPHAR_LIGAND_ID
C490954 MESH_SUPPLEMENTAL_RECORD_UI

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
Halaven HUMAN PRESCRIPTION DRUG LABEL 1 43624-002 INJECTION 0.50 mg INTRAVENOUS NDA 2 sections
Halaven HUMAN PRESCRIPTION DRUG LABEL 1 62856-389 INJECTION 0.50 mg INTRAVENOUS NDA 17 sections