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Identification
NameVinorelbine
Accession NumberDB00361  (APRD00101)
TypeSmall Molecule
GroupsApproved, Investigational
Description

Vinorelbine (Navelbine®) is an anti-mitotic chemotherapy drug that is given as a treatment for some types of cancer, including breast cancer and non-small cell lung cancer. [Wikipedia]

Structure
Thumb
Synonyms
5'-Noranhydrovinblastine
Nor-5'-anhydrovinblastine
Vinorelbin
Vinorelbina
Vinorelbine
Vinorelbinum
External Identifiers
  • KW 2307 base
  • KW-2307
  • UNII-253GQW851Q
  • UNII-Q6C979R91Y
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Aj-vinorelbinesolution10 mgintravenousAgila Jamp Canada IncNot applicableNot applicableCanada
Navelbineinjection10 mg/mLintravenousPierre Fabre Pharmaceuticals, Inc.2005-11-15Not applicableUs
Navelbinesolution10 mgintravenousPierre Fabre Pharma Canada Inc1994-12-312012-10-01Canada
Vinorelbine Injectionsolution10 mgintravenousFresenius Kabi Canada Ltd2009-03-31Not applicableCanada
Vinorelbine Injection, USPsolution10 mgintravenousGeneric Medical Partners IncNot applicableNot applicableCanada
Vinorelbine Injection, USPsolution10 mgintravenousMylan Pharmaceuticals UlcNot applicableNot applicableCanada
Vinorelbine Tartrate for Injectionsolution10 mgintravenousTeva Canada Limited2007-05-09Not applicableCanada
Vinorelbine Tartrate for Injectionsolution10 mgintravenousHospira Healthcare Corporation2004-12-22Not applicableCanada
Vinorelbine Tartrate Injection USPsolution10 mgintravenousSandoz Canada IncorporatedNot applicableNot applicableCanada
Approved Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Vinorelbineinjection, solution10 mg/mLintravenousActavis Pharma, Inc.2009-09-14Not applicableUs
Vinorelbineinjection, solution10 mg/mLintravenousSagent Pharmaceuticals2014-09-15Not applicableUs
Vinorelbineinjection, solution10 mg/mLintravenousHospira Worldwide, Inc.2005-06-02Not applicableUs
Vinorelbineinjection, solution, concentrate50 mg/5mLintravenousTeva Parenteral Medicines, Inc.2003-03-01Not applicableUs
Vinorelbineinjection, solution10 mg/mLintravenousMylan Institutional LLC2012-09-01Not applicableUs
Vinorelbineinjection, solution, concentrate10 mg/mLintravenousTeva Parenteral Medicines, Inc.2003-03-01Not applicableUs
Vinorelbineinjection, solution10 mg/mLintravenousMylan Institutional LLC2012-09-01Not applicableUs
Vinorelbineinjection, solution10 mg/mLintravenousPfizer Laboratories Div Pfizer Inc.2012-09-01Not applicableUs
Vinorelbineinjection, solution10 mg/mLintravenousMylan Institutional LLC2012-09-01Not applicableUs
Vinorelbineinjection, solution10 mg/mLintravenousPfizer Laboratories Div Pfizer Inc.2012-09-01Not applicableUs
Vinorelbineinjection, solution10 mg/mLintravenousMylan Institutional LLC2012-09-01Not applicableUs
Vinorelbineinjection, solution10 mg/mLintravenousPfizer Laboratories Div Pfizer Inc.2012-09-01Not applicableUs
Vinorelbine Tartrateinjection, solution10 mg/mLintravenousSandoz Inc.2008-02-13Not applicableUs
Vinorelbine Tartrateinjection, solution10 mg/mLintravenousWyeth Pharmaceuticals Company2008-02-13Not applicableUs
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
BendarelbinBendalis
EberelbinEbewe
EunexonAC Farma
EurovinorelbinLapharm
FilcrinFilaxis
NavelbinPierre Fabre
NavildezCryopharma
NavinCancernova
Navirelmedac
NeocitecSandoz
RenovelMustafa Nevzat
RiborelbinRibosepharm
VilneDosa
VinelbineGP-Pharm
VinorayneHospira
VinorelEriochem
VinorgenBago
VinotelFresenius
ZinavinNovamed
Brand mixturesNot Available
Salts
Name/CASStructureProperties
Vinorelbine Ditartrate
ThumbNot applicableDBSALT001060
Vinorelbine Tartrate
Thumb
  • InChI Key: CILBMBUYJCWATM-KRQCOKQWSA-N
  • Monoisotopic Mass: 1078.427040572
  • Average Mass: 1079.1059
DBSALT000447
Categories
UNIIQ6C979R91Y
CAS number71486-22-1
WeightAverage: 778.9323
Monoisotopic: 778.394164724
Chemical FormulaC45H54N4O8
InChI KeyInChIKey=GBABOYUKABKIAF-GHYRFKGUSA-N
InChI
InChI=1S/C45H54N4O8/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/h10-15,19-21,28,37-39,46,53H,8-9,16-18,22-25H2,1-7H3/t28-,37-,38+,39+,42+,43+,44-,45+/m0/s1
IUPAC Name
methyl (1R,9R,10R,11R,12R,19R)-11-(acetyloxy)-12-ethyl-4-[(12S,14R)-16-ethyl-12-(methoxycarbonyl)-1,10-diazatetracyclo[12.3.1.0³,¹¹.0⁴,⁹]octadeca-3(11),4,6,8,15-pentaen-12-yl]-10-hydroxy-5-methoxy-8-methyl-8,16-diazapentacyclo[10.6.1.0¹,⁹.0²,⁷.0¹⁶,¹⁹]nonadeca-2,4,6,13-tetraene-10-carboxylate
SMILES
[H][C@@]12N(C)C3=CC(OC)=C(C=C3[C@@]11CCN3CC=C[C@@](CC)([C@@H](OC(C)=O)[C@@]2(O)C(=O)OC)[C@@]13[H])[C@]1(C[C@@]2([H])CN(CC(CC)=C2)CC2=C1NC1=CC=CC=C21)C(=O)OC
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as vinca alkaloids. These are alkaloids with a dimeric chemical structure composed of an indole nucleus (catharanthine), and a dihydroindole nucleus (vindoline), joined together.
KingdomOrganic compounds
Super ClassAlkaloids and derivatives
ClassVinca alkaloids
Sub ClassNot Available
Direct ParentVinca alkaloids
Alternative Parents
Substituents
  • Vinca alkaloid skeleton
  • Catharanthine skeleton
  • Carbazole
  • Indole or derivatives
  • Indole
  • Dialkylarylamine
  • Anisole
  • Aralkylamine
  • Tetrahydropyridine
  • Alkyl aryl ether
  • Benzenoid
  • N-alkylpyrrolidine
  • Dicarboxylic acid or derivatives
  • Heteroaromatic compound
  • Acetate salt
  • Methyl ester
  • Tertiary alcohol
  • Pyrrolidine
  • Pyrrole
  • Cyclic alcohol
  • Tertiary aliphatic amine
  • Tertiary amine
  • Carboxylic acid ester
  • Azacycle
  • Organoheterocyclic compound
  • Ether
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Amine
  • Alcohol
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Pharmacology
IndicationFor the treatment of non-small-cell lung carcinoma.
PharmacodynamicsVinorelbine is a vinca alkaloid antineoplastic agent used as a treatment for various cancers including breast cancer, Hodgkin's disease, Kaposi's sarcoma, and testicular cancer. The vinca alkaloids are structurally similar compounds comprised of 2 multiringed units, vindoline and catharanthine. The vinca alkaloids have become clinically useful since the discovery of their antitumour properties in 1959. Initially, extracts of the periwinkle plant (Catharanthus roseus) were investigated because of putative hypoglycemic properties, but were noted to cause marrow suppression in rats and antileukemic effects in vitro. Vinorelbine binds to the microtubular proteins of the mitotic spindle, leading to crystallization of the microtubule and mitotic arrest or cell death. Vinorelbine has some immunosuppressant effect. The vinca alkaloids are considered to be cell cycle phase-specific.
Mechanism of actionThe antitumor activity of vinorelbine is thought to be due primarily to inhibition of mitosis at metaphase through its interaction with tubulin. Vinorelbine binds to the microtubular proteins of the mitotic spindle, leading to crystallization of the microtubule and mitotic arrest or cell death. Like other vinca alkaloids, vinorelbine may also interfere with: 1) amino acid, cyclic AMP, and glutathione metabolism, 2) calmodulin-dependent Ca2+-transport ATPase activity, 3) cellular respiration, and 4) nucleic acid and lipid biosynthesis.
Related Articles
AbsorptionNot Available
Volume of distribution
  • 25.4 to 40.1 L/kg
Protein binding~27%
MetabolismNot Available
Route of eliminationVinorelbine undergoes substantial hepatic elimination in humans, with large amounts recovered in feces after intravenous administration to humans.
Half life27.7-43.6 hours
Clearance
  • 0.97 – 1.26 L/hr/kg
ToxicityNot Available
Affected organisms
  • Humans and other mammals
Pathways
PathwayCategorySMPDB ID
Vinorelbine Action PathwayDrug actionSMP00439
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.974
Blood Brain Barrier-0.8815
Caco-2 permeable+0.5602
P-glycoprotein substrateSubstrate0.9283
P-glycoprotein inhibitor IInhibitor0.7488
P-glycoprotein inhibitor IIInhibitor0.7388
Renal organic cation transporterNon-inhibitor0.6979
CYP450 2C9 substrateNon-substrate0.8513
CYP450 2D6 substrateSubstrate0.6471
CYP450 3A4 substrateSubstrate0.7247
CYP450 1A2 substrateNon-inhibitor0.8415
CYP450 2C9 inhibitorNon-inhibitor0.7863
CYP450 2D6 inhibitorNon-inhibitor0.8369
CYP450 2C19 inhibitorNon-inhibitor0.8381
CYP450 3A4 inhibitorNon-inhibitor0.8095
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.6672
Ames testNon AMES toxic0.8064
CarcinogenicityNon-carcinogens0.9299
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.8350 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9014
hERG inhibition (predictor II)Non-inhibitor0.5171
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
Manufacturers
  • Pierre fabre medicament
  • Actavis totowa llc
  • App pharmaceuticals llc
  • Baxter healthcare corp anesthesia and critical care
  • Bedford laboratories div ben venue laboratories inc
  • Ebewe pharma ges mbh nfg kg
  • Hospira inc
  • Teva parenteral medicines inc
Packagers
Dosage forms
FormRouteStrength
Injectionintravenous10 mg/mL
Injection, solution, concentrateintravenous10 mg/mL
Injection, solution, concentrateintravenous50 mg/5mL
Injection, solutionintravenous10 mg/mL
Solutionintravenous10 mg
Prices
Unit descriptionCostUnit
Navelbine 50 mg/5 ml vial42.0USD ml
Vinorelbine 50 mg/5 ml vial27.6USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
logP4Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0122 mg/mLALOGPS
logP4.39ALOGPS
logP4.65ChemAxon
logS-4.8ALOGPS
pKa (Strongest Acidic)10.87ChemAxon
pKa (Strongest Basic)8.72ChemAxon
Physiological Charge2ChemAxon
Hydrogen Acceptor Count8ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area133.87 Å2ChemAxon
Rotatable Bond Count10ChemAxon
Refractivity216.99 m3·mol-1ChemAxon
Polarizability84.7 Å3ChemAxon
Number of Rings9ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis ReferenceNot Available
General References
  1. Marty M, Fumoleau P, Adenis A, Rousseau Y, Merrouche Y, Robinet G, Senac I, Puozzo C: Oral vinorelbine pharmacokinetics and absolute bioavailability study in patients with solid tumors. Ann Oncol. 2001 Nov;12(11):1643-9. [PubMed:11822766 ]
External Links
ATC CodesL01CA04
AHFS Codes
  • 10:00.00
PDB Entries
FDA labelDownload (102 KB)
MSDSNot Available
Interactions
Drug Interactions
Drug
AprepitantThe serum concentration of Vinorelbine can be increased when it is combined with Aprepitant.
AripiprazoleThe serum concentration of Aripiprazole can be increased when it is combined with Vinorelbine.
BexaroteneThe serum concentration of Vinorelbine can be decreased when it is combined with Bexarotene.
BosentanThe serum concentration of Vinorelbine can be decreased when it is combined with Bosentan.
CisplatinThe risk or severity of adverse effects can be increased when Cisplatin is combined with Vinorelbine.
ClarithromycinThe serum concentration of Vinorelbine can be increased when it is combined with Clarithromycin.
ClozapineThe risk or severity of adverse effects can be increased when Vinorelbine is combined with Clozapine.
ConivaptanThe serum concentration of Vinorelbine can be increased when it is combined with Conivaptan.
DabrafenibThe serum concentration of Vinorelbine can be decreased when it is combined with Dabrafenib.
DasatinibThe serum concentration of Vinorelbine can be increased when it is combined with Dasatinib.
DeferasiroxThe serum concentration of Vinorelbine can be decreased when it is combined with Deferasirox.
DenosumabThe risk or severity of adverse effects can be increased when Denosumab is combined with Vinorelbine.
FluconazoleThe metabolism of Vinorelbine can be decreased when combined with Fluconazole.
FosaprepitantThe serum concentration of Vinorelbine can be increased when it is combined with Fosaprepitant.
Fusidic AcidThe serum concentration of Vinorelbine can be increased when it is combined with Fusidic Acid.
GefitinibGefitinib may increase the neutropenic activities of Vinorelbine.
IdelalisibThe serum concentration of Vinorelbine can be increased when it is combined with Idelalisib.
ItraconazoleThe risk or severity of adverse effects can be increased when Itraconazole is combined with Vinorelbine.
IvacaftorThe serum concentration of Vinorelbine can be increased when it is combined with Ivacaftor.
LeflunomideThe risk or severity of adverse effects can be increased when Vinorelbine is combined with Leflunomide.
LuliconazoleThe serum concentration of Vinorelbine can be increased when it is combined with Luliconazole.
MetamizoleThe risk or severity of adverse effects can be increased when Metamizole is combined with Vinorelbine.
MifepristoneThe serum concentration of Vinorelbine can be increased when it is combined with Mifepristone.
MitomycinThe risk or severity of adverse effects can be increased when Vinorelbine is combined with Mitomycin.
MitotaneThe serum concentration of Vinorelbine can be decreased when it is combined with Mitotane.
NatalizumabThe risk or severity of adverse effects can be increased when Vinorelbine is combined with Natalizumab.
NelfinavirThe metabolism of Vinorelbine can be decreased when combined with Nelfinavir.
NetupitantThe serum concentration of Vinorelbine can be increased when it is combined with Netupitant.
PaclitaxelPaclitaxel may increase the neurotoxic activities of Vinorelbine.
PalbociclibThe serum concentration of Vinorelbine can be increased when it is combined with Palbociclib.
PhenytoinThe metabolism of Vinorelbine can be increased when combined with Phenytoin.
PimecrolimusThe risk or severity of adverse effects can be increased when Pimecrolimus is combined with Vinorelbine.
PosaconazoleThe risk or severity of adverse effects can be increased when Posaconazole is combined with Vinorelbine.
RoflumilastRoflumilast may increase the immunosuppressive activities of Vinorelbine.
SiltuximabThe serum concentration of Vinorelbine can be decreased when it is combined with Siltuximab.
SimeprevirThe serum concentration of Vinorelbine can be increased when it is combined with Simeprevir.
Sipuleucel-TThe therapeutic efficacy of Sipuleucel-T can be decreased when used in combination with Vinorelbine.
St. John's WortThe serum concentration of Vinorelbine can be decreased when it is combined with St. John's Wort.
StiripentolThe serum concentration of Vinorelbine can be increased when it is combined with Stiripentol.
TacrolimusThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Vinorelbine.
TocilizumabThe serum concentration of Vinorelbine can be decreased when it is combined with Tocilizumab.
TofacitinibVinorelbine may increase the immunosuppressive activities of Tofacitinib.
TrastuzumabTrastuzumab may increase the neutropenic activities of Vinorelbine.
VoriconazoleThe risk or severity of adverse effects can be increased when Voriconazole is combined with Vinorelbine.
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
inhibitor
General Function:
Ubiquitin protein ligase binding
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.
Gene Name:
TUBB
Uniprot ID:
P07437
Molecular Weight:
49670.515 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423 ]
  3. Kruczynski A, Barret JM, Etievant C, Colpaert F, Fahy J, Hill BT: Antimitotic and tubulin-interacting properties of vinflunine, a novel fluorinated Vinca alkaloid. Biochem Pharmacol. 1998 Mar 1;55(5):635-48. [PubMed:9515574 ]
  4. Chang AY, Garrow GC: Pilot study of vinorelbine (Navelbine) and paclitaxel (Taxol) in patients with refractory breast cancer and lung cancer. Semin Oncol. 1995 Apr;22(2 Suppl 5):66-70; discussion 70-1. [PubMed:7740336 ]
  5. Seve P, Dumontet C: [Class III beta tubulin expression in nonsmall cell lung cancer]. Rev Mal Respir. 2010 Apr;27(4):383-6. doi: 10.1016/j.rmr.2010.03.006. Epub 2010 Mar 25. [PubMed:20403547 ]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrateinhibitor
General Function:
Vitamin d3 25-hydroxylase activity
Specific Function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiot...
Gene Name:
CYP3A4
Uniprot ID:
P08684
Molecular Weight:
57342.67 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrateinhibitor
General Function:
Steroid hydroxylase activity
Specific Function:
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants.
Gene Name:
CYP2D6
Uniprot ID:
P10635
Molecular Weight:
55768.94 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Xenobiotic-transporting atpase activity
Specific Function:
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name:
ABCB1
Uniprot ID:
P08183
Molecular Weight:
141477.255 Da
References
  1. Polli JW, Wring SA, Humphreys JE, Huang L, Morgan JB, Webster LO, Serabjit-Singh CS: Rational use of in vitro P-glycoprotein assays in drug discovery. J Pharmacol Exp Ther. 2001 Nov;299(2):620-8. [PubMed:11602674 ]
Comments
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Drug created on June 13, 2005 07:24 / Updated on March 17, 2014 16:12