Eribulin

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C40H59NO11
Molecular Weight	729.8966
Optical Activity	UNSPECIFIED
Defined Stereocenters	19 / 19
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

SMILES

[H][C@]12C[C@H]3O[C@H](C[C@@H](C)C3=C)CC[C@@H]4O[C@H](CC4=C)CC[C@@]56C[C@H]7O[C@H]8[C@@H](O5)[C@@]9([H])O[C@H](CC[C@]9([H])O[C@@]8([H])[C@H]7O6)CC(=O)C[C@@H]1[C@@H](OC)[C@@H](C[C@H](O)CN)O2

InChI

InChIKey=UFNVPOGXISZXJD-JBQZKEIOSA-N

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

HIDE SMILES / InChI

Molecular Formula	C40H59NO11
Molecular Weight	729.8966
Charge	0
Count	MOL RATIO 1 MOL RATIO (average)

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	19 / 19
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description

ERIBULIN MESYLATE (HALAVEN®) is a microtubule dynamics inhibitor. It is a synthetic analog of halichondrin B, a product isolated from the marine sponge Halichondria okadai. ERIBULIN MESYLATE (HALAVEN®) inhibits the growth phase of microtubules without affecting the shortening phase and sequesters tubulin into nonproductive aggregates. It 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 the prolonged mitotic blockage. ERIBULIN MESYLATE (HALAVEN®) is 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. It is also indicated for the treatment of patients with unresectable or metastatic liposarcoma who have received a prior anthracycline-containing regimen.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Tubulin beta-1 chain 9	Inhibitor 8,297		1.4 µM [IC50]
Apoptosis 155	Activator 1,430

Conditions

Condition	Modality	Targets	Highest Phase	Product
Breast Cancer 3	Primary		Approved 8,429	HALAVEN

C_max

Value	Dose	Co-administered	Analyte	Population
1213.3 ng/mL	1.5 mg/m² 2 times / 4 weeks multiple, intravenous		ERIBULIN plasma	Homo sapiens

AUC

Value	Dose	Co-administered	Analyte	Population
32364.4 ng × h/mL	1.5 mg/m² 2 times / 4 weeks multiple, intravenous		ERIBULIN plasma	Homo sapiens

T_1/2

Value	Dose	Co-administered	Analyte	Population
28.07 h	1.5 mg/m² 2 times / 4 weeks multiple, intravenous		ERIBULIN plasma	Homo sapiens

F_unbound

Value	Dose	Co-administered	Analyte	Population
43%			ERIBULIN plasma	Homo sapiens

Doses

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Dose	Population	Adverse events
1.4 mg/m2 2 times / 3 weeks steady, intravenous Recommended	unhealthy, 55 years (range: 28 - 85 years) n = 508	Disc. AE: Neurotoxicity, Elevated liver enzymes...
1 mg/m2 3 times / 3 weeks multiple, intravenous MTD	unhealthy, 57.4 years n = 9	DLT: Fatigue, Anorexia... Other AEs: Vomiting, Nausea...
0.5 mg/m2 3 times / 3 weeks multiple, intravenous	unhealthy, 57.4 years n = 8	DLT: Fatigue...
1.4 mg/m2 3 times / 3 weeks multiple, intravenous	unhealthy, 57.4 years n = 9	DLT: Neutropenia, Fatigue...
1.4 mg/m2 2 times / 3 weeks steady, intravenous Recommended	unhealthy, 58 years (range: 26 to 91 years) n = 503	Disc. AE: Peripheral neuropathy, Neutropenia...

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AEs

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AE	Significance	Dose	Population
Elevated liver enzymes	1% Disc. AE	1.4 mg/m2 2 times / 3 weeks steady, intravenous Recommended	unhealthy, 55 years (range: 28 - 85 years) n = 508
Neurotoxicity	6% Disc. AE	1.4 mg/m2 2 times / 3 weeks steady, intravenous Recommended	unhealthy, 55 years (range: 28 - 85 years) n = 508
Alopecia	grade 1-2, 11%	1 mg/m2 3 times / 3 weeks multiple, intravenous MTD	unhealthy, 57.4 years n = 9
Anemia	grade 1-2, 11%	1 mg/m2 3 times / 3 weeks multiple, intravenous MTD	unhealthy, 57.4 years n = 9
Neutropenia	grade 1-2, 22%	1 mg/m2 3 times / 3 weeks multiple, intravenous MTD	unhealthy, 57.4 years n = 9

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Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1,737 inducer 781 inhibitor 1,587	inducer 389 inhibitor 1,767	inhibitor 1,852	inhibitor 1,612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 1,524 CYP2C19 1,478 CYP2E1 882 P-gp 1,461	P-gp 1,537	CYP1A 56 CYP2C19 293

Drug as perpetrator

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Target	Modality	Activity
CYP1A 121	inducer 1,573	no
CYP1A2 1,692	inhibitor 3,277	no
CYP2C19 1,553	inducer 1,573	no
CYP2C19 1,553	inhibitor 3,277	no
CYP2C9 1,819	inducer 1,573	no

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Drug as victim

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Target	Modality	Activity	Metabolite	Clinical evidence
CYP3A4 1,737	substrate 3,367	major		unlikely (co-administration study)
P-gp 1,537	substrate 3,367	yes [Inhibition 0.002 uM]

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Tox targets

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Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1,647	inhibitor 1,626

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Sourcing

Sourcing

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Vendor/Aggregator	ID	URL
ChEBI	CHEBI:63587	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:63587
ChemicalBook	CB22546700	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB22546700
ZINC	ZINC000169344691	http://zinc15.docking.org/substances/ZINC000169344691

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PubMed

PubMed

Title	Date	PubMed
No data available in table

Sample Use Guides

In Vivo Use Guide

Administer HALAVEN® 1.4 mg/m2 intravenously over 2 to 5 minutes on Days 1 and 8 of a 21-day cycle.

Route of Administration: Intravenous

Substance Class	Chemical
Record UNII	LR24G6354G
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

Eribulin

Official Name

English

Eribulin [WHO-DD]

Common Name

English

E-7389 free base

Code

English

ERIBULIN [VANDF]

Common Name

English

ER-086526

Code

English

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Classification Tree

Code System

Code

Breast Cancer

LIVERTOX

NBK548316

Established Pharmacologic Class

NDF-RT

N0000175592

Tubulin Binding Agent

NCI_THESAURUS

C67422

Other antineoplastic agents

WHO-ATC

L01XX41

Other antineoplastic agents

WHO-VATC

QL01XX41

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Code System

Code

Type

Description

WIKIPEDIA

ERIBULIN

PRIMARY

SMS_ID

100000115493

PRIMARY

IUPHAR

6813

PRIMARY

PUBCHEM

11354606

PRIMARY

RXCUI

1045453

PRIMARY

RxNorm

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Related Record

Type

Details


					PUO0521HZV

CYTOCHROME P450 3A4

METABOLIC ENZYME -> INHIBITOR

Comments:

Eribulin inhibited CYP3A4 activity with an apparent inhibition constant (Ki) value ranging from 3 μM to 30 μM (2190 ng/mL to 21,900 ng/mL), and the inhibition was demonstrated to be reversible and competitive.

Qualification:

Ki

Amount:

[3 to 30] MICROMOLAR (average)


					LR24G6354G

Eribulin

EXCRETED UNCHANGED

Qualification:

FECAL

Amount:

71 % (average)


					74UG0EWZ60

TUBULIN BETA CHAIN

TARGET -> INHIBITOR

Amount:


					AV9U0660CW

Eribulin Mesylate

SALT/SOLVATE -> PARENT

Amount:


					PUO0521HZV

CYTOCHROME P450 3A4

METABOLIC ENZYME -> SUBSTRATE

Interaction Type:

MAJOR

Amount:

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Related Record

Type

Details


					LR24G6354G

Eribulin

ACTIVE MOIETY

Amount:

Showing 1 to 1 of 1 entries

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Name	Property Type	Amount	Parameters
Tmax	PHARMACOKINETIC	0.1 hours [0.07 to 0.2] (average)

Volume of Distribution	PHARMACOKINETIC	[43 to 114] L/m2 (average)	AT STEADY-STATE

Biological Half-life	PHARMACOKINETIC	45.6 hours (average)

SMILES

InChI

Originator

Approval Year

Targets

Conditions

Cmax

AUC

T1/2

Funbound

Doses

AEs

Overview

OverviewOther

Drug as perpetrator​

Drug as victim

Tox targets

Sourcing

PubMed

Sample Use Guides

C_max

T_1/2

F_unbound

Drug as perpetrator