Eribulin

Identification

Name
Eribulin
Accession Number
DB08871  (DB04940)
Type
Small Molecule
Groups
Approved, 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 [2].

Structure
Thumb
Synonyms
Not Available
External IDs
ER-086526
Product Ingredients
IngredientUNIICASInChI Key
Eribulin mesylateAV9U0660CW441045-17-6QAMYWGZHLCQOOJ-WRNBYXCMSA-N
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, solution0.44 mg/mlIntravenousEisai Europe Ltd2011-03-17Not applicableEu
HalavenInjection, solution0.44 mg/mlIntravenousEisai Europe Ltd2011-03-17Not applicableEu
HalavenInjection.5 mg/mLIntravenousEisai Limited2010-11-15Not applicableUs
Categories
UNII
LR24G6354G
CAS number
253128-41-5
Weight
Average: 729.8966
Monoisotopic: 729.408811735
Chemical Formula
C40H59NO11
InChI Key
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

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.

Structured Indications
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 AvailableHuman
UTubulin beta-1 chainNot AvailableHuman
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]

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
DrugInteractionDrug group
AcetyldigitoxinAcetyldigitoxin may decrease the cardiotoxic activities of Eribulin.Approved
AcetyldigoxinAcetyldigoxin may decrease the cardiotoxic activities of Eribulin.Experimental
AmiodaroneEribulin may increase the QTc-prolonging activities of Amiodarone.Approved, Investigational
AnagrelideEribulin may increase the QTc-prolonging activities of Anagrelide.Approved
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
BCG vaccineThe therapeutic efficacy of BCG vaccine 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
CymarinCymarin may decrease the cardiotoxic activities of Eribulin.Experimental
DeslanosideDeslanoside may decrease the cardiotoxic activities of Eribulin.Approved
DigitoxinDigitoxin may decrease the cardiotoxic activities of Eribulin.Approved, Investigational
DigoxinDigoxin may decrease the cardiotoxic activities of Eribulin.Approved
Digoxin Immune Fab (Ovine)Digoxin Immune Fab (Ovine) 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
GitoformateGitoformate may decrease the cardiotoxic activities of Eribulin.Experimental
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
Lanatoside CLanatoside C may decrease the cardiotoxic activities of Eribulin.Experimental
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.Investigational, Withdrawn
MethadoneEribulin may increase the QTc-prolonging activities of Methadone.Approved
MetildigoxinMetildigoxin may decrease the cardiotoxic activities of Eribulin.Experimental
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
OleandrinOleandrin may decrease the cardiotoxic activities of Eribulin.Experimental, Investigational
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
PeruvosidePeruvoside may decrease the cardiotoxic activities of Eribulin.Experimental
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
ProscillaridinProscillaridin may decrease the cardiotoxic activities of Eribulin.Experimental
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, Withdrawn
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 Interactions
Not Available

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]
External Links
KEGG Drug
D08914
PubChem Compound
73425383
PubChem Substance
175427126
ChemSpider
32813307
ChEBI
63587
ChEMBL
CHEMBL1683590
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
PDRhealth
PDRhealth Drug Page
Wikipedia
Eribulin
ATC Codes
L01XX41 — Eribulin
AHFS Codes
  • 10:00.00 — Antineoplastic Agents
FDA label
Download (194 KB)
MSDS
Download (120 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1Active Not RecruitingTreatmentAdult Solid Neoplasm / Recurrent Ovarian Carcinoma / Recurrent Uterine Corpus Carcinoma / Stage III Ovarian Cancer / Stage III Uterine Corpus Cancer / Stage IV Ovarian Cancer / Stage IV Uterine Corpus Cancer1
1Active Not RecruitingTreatmentCancer, Breast1
1Active Not RecruitingTreatmentCancer, Breast / Lung Cancer Non-Small Cell Cancer (NSCLC) / Ovarian Epithelial Cancer Recurrent / Prostate Cancer / Prostatic Neoplasms / Sarcomas / Transitional Cell Carcinoma1
1CompletedTreatmentAdvanced Solid Tumors3
1CompletedTreatmentCancer, Breast1
1CompletedTreatmentCancers3
1CompletedTreatmentNeoplasms1
1CompletedTreatmentTumors1
1CompletedTreatmentUnspecified Adult Solid Tumor, Protocol Specific3
1RecruitingBasic ScienceSoft Tissue Sarcoma Adult1
1RecruitingTreatmentAdvanced Cancers1
1RecruitingTreatmentBreast Adenocarcinoma / Cancer, Breast / Human Epidermal Growth Factor 2 Negative Carcinoma of Breast / Recurrent Breast Carcinoma / Stage IV Breast Cancer1
1RecruitingTreatmentBreast Adenocarcinoma / Estrogen Receptor Negative / HER2/Neu Negative / Progesterone Receptor-negative / Stage IV Breast Cancer / Triple-Negative Breast Carcinoma1
1RecruitingTreatmentMalignant Lymphomas / Pediatric Cancer / Tumors, Solid1
1RecruitingTreatmentPediatrics / Tumors, Solid1
1RecruitingTreatmentRefractory Solid Tumors / Relapsed Solid Tumors1
1RecruitingTreatmentTriple Negative Breast Cancer (TNBC)1
1RecruitingTreatmentTumors, Solid1
1, 2Active Not RecruitingTreatmentDistal Urethral Carcinoma / Infiltrating Bladder Urothelial Carcinoma Associated With Urethral Carcinoma / Metastatic Urothelial Carcinoma of the Renal Pelvis and Ureter / Proximal Urethral Carcinoma / Recurrent Bladder Carcinoma / Recurrent Bladder Urothelial Carcinoma / Recurrent Urethra Carcinoma / Recurrent Urethral Urothelial Carcinoma / Recurrent Urothelial Carcinoma of the Renal Pelvis and Ureter / Regional Urothelial Carcinoma of the Renal Pelvis and Ureter / Renal Failure / Stage III Bladder Cancer / Stage III Bladder Urothelial Carcinoma / Stage III Urethral Cancer / Stage IV Bladder Cancer / Stage IV Bladder Urothelial Carcinoma / Stage IV Urethral Cancer / Ureter Carcinoma / Urothelial carcinoma ureter metastatic1
1, 2RecruitingTreatmentCancer, Breast1
1, 2RecruitingTreatmentMetastatic Breast Cancer (MBC)3
1, 2RecruitingTreatmentNon-rhabdomyosarcoma Soft Tissue Sarcomas / Refractory or Recurrent Solid Tumors / Rhabdomyosarcomas1
1, 2TerminatedTreatmentHER-2 Positive Breast Cancer1
1, 2Unknown StatusTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)1
1, 2WithdrawnTreatmentCancer of the Breast1
2Active Not RecruitingTreatmentCancer, Breast4
2Active Not RecruitingTreatmentEstrogen Receptor-negative Breast Cancer / HER2-Negative Breast Cancer / Male Breast Cancer / Progesterone Receptor-negative Breast Cancer / Stage IA Breast Cancer / Stage IB Breast Cancer / Stage II Breast Cancer / Stage IIIA Breast Cancer / Stage IIIB Breast Cancer / Stage IIIC Breast Cancer / Triple-Negative Breast Cancer (TNBC)1
2Active Not RecruitingTreatmentHER-2 Positive Breast Cancer1
2Active Not RecruitingTreatmentHer2normal1
2Active Not RecruitingTreatmentMetastatic Breast Cancer (MBC)2
2Active Not RecruitingTreatmentMetastatic Ureteral Neoplasm / Metastatic Urethral Neoplasm / Stage III Bladder Urothelial Carcinoma / Stage III Ureter Cancer / Stage III Urethral Cancer / Stage IV Bladder Urothelial Carcinoma / Stage IV Ureter Cancer / Stage IV Urethral Cancer / Ureter Urothelial Carcinoma / Urethral Urothelial Carcinoma1
2Active Not RecruitingTreatmentRecurrent Salivary Gland Cancer / Stage IVA Salivary Gland Cancer / Stage IVB Salivary Gland Cancer / Stage IVC Salivary Gland Cancer1
2CompletedTreatmentAdenocarcinoma of the Pancreas / Malignant Neoplasm of Pancreas / Recurrent Pancreatic Cancer / Stage II Pancreatic Cancer / Stage III Pancreatic Cancer / Stage IV Pancreatic Cancer1
2CompletedTreatmentAdenocarcinoma of the Prostate / Hormone-Refractory Prostate Cancer / Recurrent Prostate Cancer / Stage IV Prostate Cancer1
2CompletedTreatmentCancer, Breast5
2CompletedTreatmentCancer, Breast / Estrogen Receptor Positive Tumor1
2CompletedTreatmentCancer, Breast / HER2-Negative Breast Cancer1
2CompletedTreatmentFallopian Tube Cancer / Primary Peritoneal Cavity Cancer / Recurrent Ovarian Epithelial Cancer1
2CompletedTreatmentHER2 Negative Breast Cancer1
2CompletedTreatmentHead and Neck Carcinoma1
2CompletedTreatmentLocally Recurrent / Metastatic Breast Cancer ( HER2 Negative)1
2CompletedTreatmentMetastatic Breast Cancer (MBC)1
2CompletedTreatmentNeoplasms, Breast1
2CompletedTreatmentProstate Cancer1
2CompletedTreatmentRecurrent Non-small Cell Lung Cancer / Stage IIIb Non-small Cell Lung Cancer / Stage IV Non-Small Cell Lung Cancer1
2CompletedTreatmentRecurrent Osteosarcoma1
2CompletedTreatmentSoft Tissue Sarcoma (STS)2
2Not Yet RecruitingTreatmentCancer, Breast1
2Not Yet RecruitingTreatmentEpithelioid Hemangioendothelioma / Hemangiosarcoma1
2Not Yet RecruitingTreatmentRecurrent Bladder Urothelial Carcinoma / Recurrent Urethral Urothelial Carcinoma / Recurrent Urothelial Carcinoma of the Renal Pelvis and Ureter / Renal Pelvis Urothelial Carcinoma / Stage III Bladder Urothelial Carcinoma / Stage III Renal Pelvis Carcinoma / Stage III Ureter Cancer / Stage III Urethral Cancer / Stage IV Bladder Urothelial Carcinoma / Stage IV Renal Pelvis Carcinoma / Stage IV Ureter Cancer / Stage IV Urethral Cancer / Ureter Urothelial Carcinoma / Urothelial carcinoma ureter metastatic1
2RecruitingTreatmentAdenocarcinomas / Cancer, Breast1
2RecruitingTreatmentCancer, Breast2
2RecruitingTreatmentCancers / Tumors, Solid1
2RecruitingTreatmentHER2-negative Circulating Tumor Cells / HER2-negative Und Hormone-receptor Positive Metastatic Breast Cancer / Postmenopausal Female Patients1
2RecruitingTreatmentHuman Epidermal Growth Factor 2 Negative Carcinoma of Breast / Inflammatory carcinoma of the breast1
2RecruitingTreatmentHuman Epidermal Growth Factor 2 Negative Carcinoma of Breast / Metastatic Breast Cancer (MBC)1
2RecruitingTreatmentMalignant Neoplasm of Breast1
2RecruitingTreatmentMetastatic Brain Tumors / Metastatic Breast Cancer (MBC)1
2RecruitingTreatmentMetastatic Breast Cancer (MBC)1
2RecruitingTreatmentRecurrent Breast Carcinoma / Stage IV Breast Cancer1
2RecruitingTreatmentRecurrent Cervical Cancer / Stage IIIA Cervical Cancer / Stage IIIB Cervical Cancer / Stage IVA Cervical Cancer / Stage IVB Cervical Cancer1
2TerminatedTreatmentCancer of the Breast / Cancer, Breast / Neoplasms, Breast / Tumors, Breast1
2TerminatedTreatmentCancer, Breast1
2WithdrawnTreatmentBRCA1 Mutations / BRCA2 Mutation / Breast Cancer Metastatic / Cancer, Ovarian1
2WithdrawnTreatmentCancer, Breast1
3Active Not RecruitingTreatmentCancer of Breast / Cancer, Breast / HER2-Negative Breast Cancer / Triple Negative Breast Cancer (TNBC) / Tumors, Breast1
3Active Not RecruitingTreatmentMetastatic Breast Cancer (MBC)1
3Active Not RecruitingTreatmentMetastatic Triple Negative Breast Cancer1
3CompletedTreatmentCancer, Breast1
3CompletedTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)1
3Not Yet RecruitingTreatmentMetastatic Breast Cancer (MBC)1
3RecruitingTreatmentCancer, Breast2
3RecruitingTreatmentCancer, Breast / Metastasis1
3RecruitingTreatmentHER-2 Positive Breast Cancer / Neoplasms, Metastatic1
3RecruitingTreatmentHER2-positive Locally Advanced or Metastatic Breast Cancer1
3RecruitingTreatmentLocally Recurrent Breast Cancer / Metastatic Breast Cancer (MBC)1
4CompletedTreatmentCancer, Breast / Neoplasms, Breast1
4RecruitingHealth Services ResearchAdverse Drug Events / Metastatic Breast Cancer (MBC) / Neurotoxicity / Therapeutic Agent Toxicity / Toxicity1
Not AvailableActive Not RecruitingTreatmentBreast Carcinoma Metastatic to the Brain / Lung Carcinoma Metastatic to the Brain / Metastatic Malignant Neoplasm in the Adult Brain / Metastatic Malignant Neoplasm to the Adult Brain / Primary Brain Tumors / Stage IV Bladder Cancer / Stage IV Non-Small Cell Lung Cancer1
Not AvailableApproved for MarketingNot AvailableMetastatic Breast Cancer (MBC)1
Not AvailableCompletedNot AvailableInoperable or Recurrent Breast Cancer1
Not AvailableCompletedTreatmentCancer, Breast1
Not AvailableRecruitingNot AvailableAdvanced Breast Cancer / Metastatic Breast Cancer (MBC)1
Not AvailableRecruitingNot AvailableCancer, Breast1
Not AvailableRecruitingNot AvailableLocally Advanced or Metastatic Breast Cancer1
Not AvailableRecruitingNot AvailableSoft Tissue Sarcoma (STS)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
InjectionIntravenous.5 mg/mL
Injection, solutionIntravenous0.44 mg/ml
SolutionIntravenous0.5 mg
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US8097648No2001-01-222021-01-22Us
US6469182No1999-06-162019-06-16Us
US7470720No1999-06-162019-06-16Us
US6214865No2003-07-202023-07-20Us

Properties

State
Liquid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0798 mg/mLALOGPS
logP1.26ALOGPS
logP2.31ChemAxon
logS-4ALOGPS
pKa (Strongest Acidic)14.81ChemAxon
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 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
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This 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.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Furopyrans
Sub Class
Not Available
Direct Parent
Furopyrans
Alternative Parents
Furofurans / 1,3-dioxepanes / 1,4-dioxepanes / Ketals / Pyrans / Oxanes / Monosaccharides / Tetrahydrofurans / Furans / Secondary alcohols
show 8 more
Substituents
Furopyran / Furofuran / 1,3-dioxepane / 1,4-dioxepane / Dioxepane / Ketal / Monosaccharide / Oxane / Pyran / Furan
show 22 more
Molecular Framework
Aliphatic heteropolycyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Human
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
Human
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 November 22, 2017 12:37