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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
SynonymLanguageCode
5'-NoranhydrovinblastineNot AvailableIS
Nor-5'-anhydrovinblastineNot AvailableNot Available
VinorelbinGermanINN
VinorelbinaSpanishINN
VinorelbineNot AvailableDCF, BAN, USP 28,
VinorelbinumLatinINN
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Navelbineinjection10 mg/mLintravenousPierre Fabre Pharmaceuticals, Inc.2005-11-15Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Vinorelbine Tartrateinjection, solution10 mg/mLintravenousWyeth Pharmaceuticals Company2008-02-13Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Vinorelbineinjection, solution10 mg/mLintravenousPfizer Laboratories Div Pfizer Inc.2012-09-01Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Vinorelbineinjection, solution10 mg/mLintravenousPfizer Laboratories Div Pfizer Inc.2012-09-01Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Vinorelbineinjection, solution10 mg/mLintravenousPfizer Laboratories Div Pfizer Inc.2012-09-01Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Vinorelbineinjection10 mg/mLintravenousTeva Parenteral Medicines, Inc.2003-03-01Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Vinorelbineinjection50 mg/5mLintravenousTeva Parenteral Medicines, Inc.2003-03-01Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Vinorelbineinjection, solution10 mg/mLintravenousSagent Pharmaceuticals2014-09-15Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Vinorelbineinjection, solution10 mg/mLintravenousActavis Pharma, Inc.2015-01-05Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Vinorelbine Tartrateinjection, solution10 mg/mLintravenousHospira Worldwide, Inc.2005-06-02Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Vinorelbine Tartrateinjection, solution10 mg/mLintravenousSandoz Inc.2008-02-13Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Vinorelbineinjection, solution10 mg/mLintravenousMylan Institutional LLC2012-09-01Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Vinorelbineinjection, solution10 mg/mLintravenousMylan Institutional LLC2012-09-01Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Vinorelbineinjection, solution10 mg/mLintravenousMylan Institutional LLC2012-09-01Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Vinorelbineinjection, solution10 mg/mLintravenousMylan Institutional LLC2012-09-01Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Over the Counter ProductsNot 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
CAS number71486-22-1
WeightAverage: 778.9323
Monoisotopic: 778.394164724
Chemical FormulaC45H54N4O8
InChI KeyGBABOYUKABKIAF-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.
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 substrateNon-inhibitor0.7863
CYP450 2D6 substrateNon-inhibitor0.8369
CYP450 2C19 substrateNon-inhibitor0.8381
CYP450 3A4 substrateNon-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
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
Injectionintravenous50 mg/5mL
Injection, solutionintravenous10 mg/mL
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 Reference
  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
External Links
ATC CodesL01CA04
AHFS Codes
  • 10:00.00
PDB Entries
FDA labelDownload (102 KB)
MSDSNot Available
Interactions
Drug Interactions
Drug
AprepitantMay increase the serum concentration of CYP3A4 Substrates.
AripiprazoleCYP3A4 Inhibitors (Weak) may increase the serum concentration of ARIPiprazole.
BosentanMay decrease the serum concentration of CYP3A4 Substrates.
CisplatinMay enhance the adverse/toxic effect of Vinorelbine. Specifically, the combination may be associated with a higher risk of granulocytopenia.
ClozapineMyelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for agranulocytosis may be increased.
ConivaptanMay increase the serum concentration of CYP3A4 Substrates.
DabrafenibMay decrease the serum concentration of CYP3A4 Substrates.
DasatinibMay increase the serum concentration of CYP3A4 Substrates.
DeferasiroxMay decrease the serum concentration of CYP3A4 Substrates.
DenosumabMay enhance the adverse/toxic effect of Immunosuppressants. Specifically, the risk for serious infections may be increased.
DofetilideCYP3A4 Inhibitors (Weak) may increase the serum concentration of Dofetilide.
FosaprepitantMay increase the serum concentration of CYP3A4 Substrates.
GefitinibGefitinib may enhance the neutropenic effect of Vinorelbine.
HydrocodoneCYP3A4 Inhibitors (Weak) may increase the serum concentration of Hydrocodone.
ItraconazoleMay enhance the adverse/toxic effect of Vinorelbine. Itraconazole may increase the serum concentration of Vinorelbine.
IvacaftorMay increase the serum concentration of CYP3A4 Substrates.
LeflunomideImmunosuppressants may enhance the adverse/toxic effect of Leflunomide. Specifically, the risk for hematologic toxicity such as pancytopenia, agranulocytosis, and/or thrombocytopenia may be increased.
LomitapideCYP3A4 Inhibitors (Weak) may increase the serum concentration of Lomitapide.
LULICONAZOLEMay increase the serum concentration of CYP3A4 Substrates.
MifepristoneMay increase the serum concentration of CYP3A4 Substrates.
MitotaneMay decrease the serum concentration of CYP3A4 Substrates.
NatalizumabImmunosuppressants may enhance the adverse/toxic effect of Natalizumab. Specifically, the risk of concurrent infection may be increased.
PimecrolimusMay enhance the adverse/toxic effect of Immunosuppressants.
PimozideCYP3A4 Inhibitors (Weak) may increase the serum concentration of Pimozide.
PosaconazoleMay enhance the adverse/toxic effect of Antineoplastic Agents (Vinca Alkaloids). Posaconazole may increase the serum concentration of Antineoplastic Agents (Vinca Alkaloids).
RoflumilastMay enhance the immunosuppressive effect of Immunosuppressants.
SiltuximabMay decrease the serum concentration of CYP3A4 Substrates.
SimeprevirMay increase the serum concentration of CYP3A4 Substrates.
Sipuleucel-TImmunosuppressants may diminish the therapeutic effect of Sipuleucel-T.
TocilizumabMay decrease the serum concentration of CYP3A4 Substrates.
TofacitinibImmunosuppressants may enhance the immunosuppressive effect of Tofacitinib.
TrastuzumabMay enhance the neutropenic effect of Immunosuppressants.
VoriconazoleMay enhance the adverse/toxic effect of Antineoplastic Agents (Vinca Alkaloids). Voriconazole may increase the serum concentration of Antineoplastic Agents (Vinca Alkaloids).
Food InteractionsNot Available

Targets

1. Tubulin beta chain

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Tubulin beta chain P07437 Details

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
  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
  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
  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
  5. Seve P, Dumontet C: [Class III beta tubulin expression in nonsmall cell lung cancer] Rev Mal Respir. 2010 Apr;27(4):383-6. Epub 2010 Mar 25. Pubmed

Enzymes

1. Cytochrome P450 3A4

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor

Components

Name UniProt ID Details
Cytochrome P450 3A4 P08684 Details

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. Epub 2009 Nov 24. Pubmed

2. Cytochrome P450 2D6

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor

Components

Name UniProt ID Details
Cytochrome P450 2D6 P10635 Details

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. Epub 2009 Nov 24. Pubmed

Transporters

1. Multidrug resistance protein 1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Multidrug resistance protein 1 P08183 Details

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

Comments
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Drug created on June 13, 2005 07:24 / Updated on March 17, 2014 16:12