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
Malignant neoplasm progression 1134.79 29.75 431 8199 64495 46612937
Neutropenia 1039.08 29.75 510 8120 142694 46534738
Febrile neutropenia 734.83 29.75 354 8276 94273 46583159
Metastases to liver 318.65 29.75 124 8506 19461 46657971
Leukopenia 307.12 29.75 178 8452 68165 46609267
Metastases to bone 303.36 29.75 116 8514 17360 46660072
Neuropathy peripheral 299.23 29.75 194 8436 90699 46586733
Breast cancer metastatic 256.17 29.75 96 8534 13582 46663850
Interstitial lung disease 214.61 29.75 130 8500 53819 46623613
Disease progression 153.03 29.75 130 8500 91170 46586262
Breast cancer 146.57 29.75 96 8534 45422 46632010
Palmar-plantar erythrodysaesthesia syndrome 129.63 29.75 67 8563 20384 46657048
Mucosal inflammation 127.40 29.75 83 8547 38893 46638539
Stomatitis 126.30 29.75 103 8527 68194 46609238
Pseudocirrhosis 123.22 29.75 28 8602 660 46676772
Osteonecrosis of jaw 111.78 29.75 73 8557 34329 46643103
Metastases to lung 110.40 29.75 49 8581 10647 46666785
Metastases to lymph nodes 97.25 29.75 39 8591 6592 46670840
Metastases to central nervous system 95.65 29.75 45 8585 11176 46666256
Neoplasm progression 87.58 29.75 57 8573 26626 46650806
Haematotoxicity 85.43 29.75 36 8594 6897 46670535
Thrombocytopenia 71.93 29.75 102 8528 126479 46550953
Pyrexia 65.94 29.75 176 8454 348626 46328806
Drug ineffective 65.65 29.75 22 8608 677816 45999616
Metastases to skin 63.18 29.75 19 8611 1361 46676071
Pleural effusion 59.60 29.75 75 8555 82877 46594555
Hormone receptor positive breast cancer 53.06 29.75 13 8617 427 46677005
Neutrophil count decreased 51.43 29.75 51 8579 43375 46634057
Anaemia 48.15 29.75 129 8501 255650 46421782
Decreased appetite 42.92 29.75 104 8526 193732 46483700
Breast cancer recurrent 40.61 29.75 18 8612 3893 46673539
Metastases to the mediastinum 37.61 29.75 10 8620 457 46676975
Polyneuropathy 36.06 29.75 24 8606 11620 46665812
Lymphopenia 34.55 29.75 26 8604 15267 46662165
Myelosuppression 34.29 29.75 20 8610 7683 46669749
Drug hypersensitivity 34.05 29.75 3 8627 243822 46433610
Bile duct stenosis 33.10 29.75 11 8619 1090 46676342
Tumour marker increased 32.64 29.75 15 8615 3526 46673906
Lymphangiosis carcinomatosa 32.50 29.75 11 8619 1153 46676279
Superior vena cava syndrome 30.91 29.75 9 8621 576 46676856
PIK3CA-activated mutation 30.67 29.75 9 8621 592 46676840
Metastases to spine 29.92 29.75 13 8617 2681 46674751
Portal hypertension 29.77 29.75 14 8616 3469 46673963

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 86.01 45.69 35 302 106658 29845483
Neutropenia 79.71 45.69 35 302 128505 29823636

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 cytostatic
CHEBI has role CHEBI:61951 microtubule destabilising role

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)

None

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
D08914 KEGG_DRUG
441045-17-6 SECONDARY_CAS_RN
4030296 VANDF
4030302 VANDF
C1506837 UMLSCUI
CHEBI:70710 CHEBI
6K9 PDB_CHEM_ID
CHEMBL1683544 ChEMBL_ID
CHEMBL1683590 ChEMBL_ID
DB08871 DRUGBANK_ID
C490954 MESH_SUPPLEMENTAL_RECORD_UI
17755248 PUBCHEM_CID
6813 IUPHAR_LIGAND_ID
8854 INN_ID
LR24G6354G UNII
1045452 RXNORM
178296 MMSL
27619 MMSL
d07716 MMSL
013558 NDDF
013559 NDDF
448800004 SNOMEDCT_US
708166000 SNOMEDCT_US
767582004 SNOMEDCT_US

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 29 sections