VINORELBINE TARTRATE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C45H54N4O8.2C4H6O6
Molecular Weight	1079.1059
Optical Activity	UNSPECIFIED
Defined Stereocenters	12 / 12
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

SMILES

O[C@H]([C@@H](O)C(O)=O)C(O)=O.O[C@H]([C@@H](O)C(O)=O)C(O)=O.CCC1=C[C@@H]2CN(C1)CC3=C(NC4=C3C=CC=C4)[C@@](C2)(C(=O)OC)C5=C(OC)C=C6N(C)[C@@H]7[C@]8(CCN9CC=C[C@](CC)([C@@H]89)[C@@H](OC(C)=O)[C@]7(O)C(=O)OC)C6=C5

InChI

InChIKey=CILBMBUYJCWATM-PYGJLNRPSA-N

InChI=1S/C45H54N4O8.2C4H6O6/c1-8-27-19-28-22-44(40(51)55-6,36-30(25-48(23-27)24-28)29-13-10-11-14-33(29)46-36)32-20-31-34(21-35(32)54-5)47(4)38-43(31)16-18-49-17-12-15-42(9-2,37(43)49)39(57-26(3)50)45(38,53)41(52)56-7;2*5-1(3(7)8)2(6)4(9)10/h10-15,19-21,28,37-39,46,53H,8-9,16-18,22-25H2,1-7H3;2*1-2,5-6H,(H,7,8)(H,9,10)/t28-,37-,38+,39+,42+,43+,44-,45-;2*1-,2-/m011/s1

HIDE SMILES / InChI

Description

Vinorelbine (trade name Navelbine) is a semi-synthetic vinca-alkaloid with a broad spectrum of anti-tumour activity. Vinorelbine is a mitotic spindle poison that impairs chromosomal segregation during mitosis. It blocks cells at G2/M. Microtubules (derived from polymers of tubulin) are the principal target of vinorelbine. Vinorelbine was developed by Pierre Fabre under licence from the CNRS in France. NAVELBINE (vinorelbine tartrate) as a single agent or in combination is indicated for the first line treatment of non small cell lung cancer and advanced breast cancer.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Tubulin 69	Inhibitor 8,504

Conditions

Condition	Modality	Targets	Highest Phase	Product
Non-small cell lung cancer 211	Primary		Approved 8,583	NAVELBINE
Breast cancer 432	Primary		Approved 8,583	NAVELBINE

C_max

Value	Dose	Co-administered	Analyte	Population
133.4 ng/mL	80 mg/m² single, oral		VINORELBINE plasma	Homo sapiens
761.8 ng/mL	25 mg/m² single, intravenous		VINORELBINE plasma	Homo sapiens

AUC

Value	Dose	Co-administered	Analyte	Population
1299 ng × h/mL	80 mg/m² single, oral		VINORELBINE plasma	Homo sapiens
1042 ng × h/mL	25 mg/m² single, intravenous		VINORELBINE plasma	Homo sapiens

T_1/2

Value	Dose	Co-administered	Analyte	Population
29.4 h	80 mg/m² single, oral		VINORELBINE plasma	Homo sapiens
37.9 h	25 mg/m² single, intravenous		VINORELBINE plasma	Homo sapiens

F_unbound

Value	Dose	Co-administered	Analyte	Population
14.6%			VINORELBINE plasma	Homo sapiens

Doses

Show entries

Dose	Population	Adverse events
30 mg/m2 1 times / week multiple, intravenous Recommended	unhealthy, 61 years (range: 32-79 years)	DLT: Neutropenia, Neutropenia... Other AEs: Leukopenia, Leukopenia...
100 mg/m2 1 times / week multiple, oral MTD	unhealthy, adult	DLT: Neutropenia... Other AEs: Leukopenia, Vomiting...
80 mg/m2 1 times / week multiple, oral RP2D	unhealthy, adult	DLT: Neutropenia, Neutropenia... Other AEs: Leukopenia, Vomiting...
25 mg/m2 1 times / week multiple, intravenous Recommended	unhealthy	DLT: Neutropenia... Other AEs: Anemia, Leukopenia...

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AEs

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AE	Significance	Dose	Population
Thrombocytopenia	grade 1, 4%	30 mg/m2 1 times / week multiple, intravenous Recommended	unhealthy, 61 years (range: 32-79 years)
Anemia	grade 1, 77%	30 mg/m2 1 times / week multiple, intravenous Recommended	unhealthy, 61 years (range: 32-79 years)
Neutropenia	grade 1, 80% DLT	30 mg/m2 1 times / week multiple, intravenous Recommended	unhealthy, 61 years (range: 32-79 years)
Leukopenia	grade 1, 81%	30 mg/m2 1 times / week multiple, intravenous Recommended	unhealthy, 61 years (range: 32-79 years)
Anemia	grade 3, 1%	30 mg/m2 1 times / week multiple, intravenous Recommended	unhealthy, 61 years (range: 32-79 years)

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Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1,946 inhibitor 2,252	substrate 1,193	substrate 1,388 inhibitor 2,507	inhibitor 2,217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP2C8/9 42 CYP2C19 2,057 CYP1A2 2,153 CYP2A6 879 CYP2E1 1,060 CYP2B6 926 P-gp 1,741 UGT 45	CYP3A 220 CYP3A5 446 CYP1A1 389 CYP1A2 1,197 CYP2A6 626 CYP2B6 776 CYP2C8 810 CYP2C19 1,119 CYP2E1 729 CYP2J2 71 CYP3A7 109 CYP4A11 137 P-gp 2,052 MRP2 252

Drug as perpetrator

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Target	Modality	Activity
CYP2B6 1,160	inhibitor 4,027	likely
CYP2C19 2,141	inhibitor 4,027	likely
CYP2C8/9 42	inhibitor 4,027	likely
CYP1A2 2,333	inhibitor 4,027	no [IC50 >10 uM]
CYP2A6 911	inhibitor 4,027	no [IC50 >10 uM]

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Drug as victim

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Target	Modality	Activity
CYP1A1 389	substrate 4,014	unlikely
CYP1A2 1,197	substrate 4,014	unlikely
CYP2A6 626	substrate 4,014	unlikely
CYP2B6 776	substrate 4,014	unlikely
CYP2C19 1,119	substrate 4,014	unlikely

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Tox targets

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Target	Modality	Activity	Metabolite	Clinical evidence
hERG 2,263	inhibitor 2,237

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Sourcing

Sourcing

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Vendor/Aggregator	ID	URL
ChEBI	CHEBI:480999	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:480999
eMolecules	36500497	https://www.emolecules.com/cgi-bin/more?vid=36500497
eMolecules	36754948	https://www.emolecules.com/cgi-bin/more?vid=36754948
MolPort	MolPort-006-823-869	https://www.molport.com/shop/molecule-link/MolPort-006-823-869
Selleck Chemicals	vinorelbine-navelbine	http://www.selleckchem.com/products/vinorelbine-navelbine.html

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PubMed

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Title	Date	PubMed
Vinorelbine, epirubicin, and methotrexate (VEM) as primary treatment in locally advanced breast cancer.	2001	11524553
Activity and safety of vinorelbine combined with doxorubicin or fluorouracil as first-line therapy in advanced breast cancer: a stratified phase II study.	2001	11423674
Carboplatin/paclitaxel or carboplatin/vinorelbine followed by accelerated hyperfractionated conformal radiation therapy: a preliminary report of a phase I dose escalation trial from the Carolina Conformal Therapy Consortium.	2001	11182001
Options in advanced non-small cell lung cancer: a review and report on a phase II study of vinorelbine plus gemcitabine.	2001	11182000
Marked antitumor activity of a new potent acronycine derivative in orthotopic models of human solid tumors.	2001 Aug	11489841

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Patents

Sample Use Guides

In Vivo Use Guide

NAVELBINE (vinorelbine tartrate) for intravenous injections is indicated for the treatment of non-small cell lung cancer. Single-Agent NAVELBINE (vinorelbine tartrate): The usual initial dose of single-agent NAVELBINE is 30 mg/m2 administered weekly. Oral NAVELBINE is indicated for the treatment of non-small cell lung cancer and advanced breast cancer. As a single agent, the recommended regimen is: First three administrations 60mg/m² of body surface area, administered once weekly. Subsequent administrations Beyond the third administration, it is recommended to increase the dose of Navelbine to 80mg/m² once weekly except in those patients for whom the neutrophil count dropped once below 500/mm3 or more than once between 500 and 1000/mm3 during the first three administrations at 60mg/m².

Route of Administration: Other

In Vitro Use Guide

IC(50) values for inhibition of HeLa cell proliferation for vinorelbine was 1.25 nM, similar to the concentrations that induced mitotic block at the metaphase/anaphase transition (3.8 nM).

Show entries

Name

Type

Language

VINORELBINE DITARTRATE

Preferred Name

English

VINORELBINE TARTRATE

Official Name

English

VINORELBINE DITARTRATE [JAN]

Common Name

English

TLC178

Code

English

VINORELBINE LIPOSOMAL

Common Name

English

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Show entries

Classification Tree

Code System

Code

Tubulin Binding Agent

NCI_THESAURUS

C67422

Alkaloid

NCI_THESAURUS

C932

Designated

FDA ORPHAN DRUG

540716

Designated

FDA ORPHAN DRUG

588417

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Show entries

Code System

Code

Type

Description

DAILYMED

253GQW851Q

PRIMARY

PUBCHEM

11607738

PRIMARY

USAN

EE-34

PRIMARY

EPA CompTox

DTXSID5047825

PRIMARY

NCI_THESAURUS

C135619

ALTERNATIVE

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ACTIVE MOIETY


					Q6C979R91Y

VINORELBINE

PARENT (SALT/SOLVATE)


					W4888I119H

Tartaric Acid

SUBSTANCE RECORD


					253GQW851Q

VINORELBINE TARTRATE

SMILES

InChI

CNS Activity

Originator

Approval Year

Targets

Conditions

Cmax

AUC

T1/2

Funbound

Doses

AEs

Overview

OverviewOther

Drug as perpetrator​

Drug as victim

Tox targets

Sourcing

PubMed

Patents

Sample Use Guides

C_max

T_1/2

F_unbound

Drug as perpetrator