Identification

Name
Vinorelbine
Accession Number
DB00361
Description

Vinorelbine is an anti-mitotic chemotherapy drug that is used in the treatment of several types of malignancies, including breast cancer and non-small cell lung cancer (NSCLC) 5. It was initially approved in the USA in 1990's for the treatment of NSCLC 13.

It is a third-generation vinca alkaloid. The introduction of third-generation drugs (vinorelbine, gemcitabine, taxanes) in platinum combination improved survival of patients with advanced NSCLC, with very similar results from the various drugs. Treatment toxicities are considerable in the combination treatment setting 2.

A study was done on the clearance rate of vinorelbine on individuals with various single polymorphonuclear mutations. It was found that there was 4.3-fold variation in vinorelbine clearance across the cohort, suggesting a strong influence of genetics on the clearance of this drug 7.

Type
Small Molecule
Groups
Approved, Investigational
Structure
Thumb
Weight
Average: 778.947
Monoisotopic: 778.394164715
Chemical Formula
C45H54N4O8
Synonyms
  • 5'-Noranhydrovinblastine
  • Vinorelbin
  • Vinorelbina
  • Vinorelbine
  • Vinorelbinum
External IDs
  • KW 2307 base

Pharmacology

Indication

Vinorelbine tartrate is indicated for adults in the treatment of advanced non-small cell lung cancer (NSCLC), as a single therapy or in combination with other chemotherapeutic drugs 5.

Used in relapsed or refractory Hodgkin lymphoma, in combination with other chemotherapy agents 14.

For the treatment of desmoid tumor or aggressive fibromatosis, in combination with methotrexate 14.

For the treatment of recurrent or metastatic squamous cell head and neck cancer 14.

For the treatment of recurrent ovarian cancer 14.

For the treatment of metastatic breast cancer, in patients previously treated with anthracyline and/or taxane therapy 14.

For the treatment of HER2-positive, trastuzumab-resistant, advanced breast cancer in patients previously treated with a taxane, in combination with trastuzumab and everolimus 14.

Associated Conditions
Contraindications & Blackbox Warnings
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Pharmacodynamics

Vinorelbine is a semi-synthetic vinca-alkaloid with a wide spectrum of anti-tumor activity. The vinca-alkaloids are considered spindle poisons. They work by interfering with the polymerization of tubulin, a protein responsible for building the microtubule system which appears during cell division in proliferating cancer cells 11.

Mechanism of action

Vinca alkaloids are structurally similar compounds composed of two multi-ringed units, vindoline, and catharanthine. Vinorelbine tartrate is a vinca alkaloid in which the catharanthine component is the target of structural modification 9, 10.

This structural modification contributes to unique pharmacologic properties.The antitumor activity of vinorelbine tartrate is believed to be owed to the inhibition of mitosis at metaphase via its interaction with tubulin 5.

Vinorelbine is a mitotic spindle poison that interferes with chromosomal segregation during mitosis, also known as cell division. It pauses cells at the G2/M phases, when present at concentrations close to the half maximal inhibitory concentration (IC50). Microtubules, which are derived from polymers of tubulin, are the main target of vinorelbine.

The chemical modification used to produce vinorelbine allows for the opening of the eight-member catharanthine ring with the formation of both a covalent and reversible bond with tubulin 11.

The relative contribution of different microtubule-associated proteins in the production of tubulin vary between neural tissue and proliferating cells and this has important functional implications. The ability of vinorelbine to bind specifically to mitotic rather than other microtubules has been shown and may suggest that neurotoxicity is less likely to be a problem than with the molecular mechanism of action 11.

As with other anti-microtubule agents, vinorelbine is known to contribute apoptosis in malignant cells. The exact mechanisms by which this process occurs are complex and many details are yet to be elucidated. The disarray of the microtubule structure has a number of effects, including the induction of tumor suppressor gene p53 and activation/inactivation of a number of protein kinases involved in essential signaling pathways, including p21 WAF1/CIP1 and Ras/Raf, PKC/PKA. These molecular changes lead to phosphorylation and consequently inactivation of the apoptosis inhibitor Bcl2. This, in turn, results in a decrease in the formation of heterodimers between Bcl2 and the pro-apoptotic gene BAX, stimulating the sequence of cell apoptosis 11.

Vinorelbine tartrate also possibly interferes with amino acid, cyclic AMP and glutathione metabolism, calmodulin-dependent Ca++-transport ATPase activity, cellular respiration, and nucleic acid and lipid biosynthesis 5.

TargetActionsOrganism
ATubulin beta chain
antagonist
inhibitor
Humans
Absorption

Vinorelbine is rapidly absorbed with peak serum concentration reached within 2 hours 5.

Vinorelbine is highly bound to platelets and lymphocytes and is also bound to alpha 1-acid glycoprotein, albumin, and lipoproteins 4.

Volume of distribution

The volume of distribution is large, indicating extensive extravascular distribution 4.

The steady-state volume of distribution values range from 25.4 to 40.1 L/kg, according to one study 7.

Widely distributed, with highest amounts found in elimination organs such as liver and kidneys, minimal in heart and brain 7.

Protein binding

80-90% 6

Metabolism

Vinorelbine undergoes substantial hepatic elimination in humans. Two metabolites of vinorelbine have been identified in human blood, plasma, and urine; vinorelbine N-oxide and deacetylvinorelbine. Deacetylvinorelbine has been demonstrated to be the primary metabolite of vinorelbine in humans, and has been shown to possess antitumor activity similar to vinorelbine 9, 10.

Vinorelbine is metabolized into two other minor metabolites, 20'-hydroxyvinorelbine and vinorelbine 6'-oxide 10.

Therapeutic doses of vinorelbine (30 mg/m2) yield very small, if any, quantifiable levels of either metabolite in blood or urine. The metabolism of vinorelbine is mediated by hepatic cytochrome P450 isoenzymes in the CYP3A subfamily 8, 4.

As the liver provides the main route for metabolism of the drug, patients with hepatic impairment may demonstrate increased toxicity with standard dosing, however, there are no available data on this. Likewise, the contribution of cytochrome P450 enzyme action to vinorelbine metabolism has potential implications in patients receiving other drugs metabolized by this route 11.

Hover over products below to view reaction partners

Route of elimination

Vinorelbine undergoes substantial hepatic elimination in humans, with large amounts recovered in feces after intravenous administration to humans 5.

Urinary excretion of unchanged drug accounts for less than 20% of an intravenous dose, with fecal elimination accounting for an additional 30% to 60% 4.

After intravenous administration of radioactive vinorelbine, approximately 18% and 46% of administered radioactivity was recovered in urine and feces, respectively 7.

Half-life

The terminal phase half-life averaged 27.7 to 43.6 hours; the mean plasma clearances ranged from 0.97 to 1.26 L/hr/kg 4.

Clearance

The plasma clearance of vinorelbine is high, approaching the same as hepatic blood flow in humans, and its volume of distribution is large, indicating extensive extravascular distribution. In comparison to vinblastine or vincristine 4.

The clearance was found to be in the range of 0.29-1./26 L/ per kg in 4 clinical trials of patients receiving 30 mg/m2 of vinorelbine 12.

Adverse Effects
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Toxicity

Due to the wide array of adverse effects of this drug, the toxicity of is categorized into organ systems 5.

Hematologic: Granulocytopenia was the primary dose-limiting toxicity with vinorelbine tartrate therapy; it is generally reversible and not cumulative. In one study, granulocytopenia resulted in hospitalizations for fever and/or sepsis in 8% of NSCLC and 9% of breast cancer patients 5. Infectious (septic) deaths occurred in about 1% of patients. Grade 3 or 4 anemia occurred in about 1% of lung cancer and approximately 14% of breast cancer patients. Blood transfusions were administered to 18% of patients who received vinorelbine tartrate therapy. The incidence of Grade 3 and 4 thrombocytopenia was found to be less than 1% 5.

Neurologic: Mild to moderate peripheral neuropathy may occur. Symptoms of paresthesia and hypesthesia are reported as the most commonly reported neurologic toxicities of this drug. The loss of deep tendon reflexes (DTR) occurs in less than 5% of patients, according to one study. The development of severe peripheral neuropathy is rare 5.

Dermatologic: Alopecia has been reported in only about 12% of patients and is usually reported as mild. Vinorelbine tartrate is a moderate vesicant, leading to injection site reactions. Symptoms include erythema, pain at the injection site and vein discoloration occurred in about 1/3 of all patients. Chemical phlebitis along the vein, near the site of injection, has been reported 5.

Respiratory: Shortness of breath was reported in 3% of NSCLC and 9% of breast cancer patients, and was severe in 2% of each patient population. Interstitial pulmonary changes have been documented in a few patients 5.

Gastrointestinal: Mild or moderate nausea symptoms occurred in 32% of NSCLC and 47% of breast cancer patients treated with vinorelbine tartrate. Severe nausea was occurred infrequently (1% and 3% in NSCLC and breast cancer patients, respectively). Prophylactic administration of anti-emetics was not routine in patients treated with single-agent vinorelbine tartrate. Constipation occurred in about 28% of NSCLC and 38% of breast cancer patients. The paralytic ileus incidence of less than 2% of patients. Vomiting, diarrhea, anorexia and stomatitis were found to be mild or moderate and occurred in less than 20% of study patients 5.

Hepatic: Transient elevations of liver enzymes were reported without clinical symptoms. Cardiovascular: Chest pain was reported in 5% of NSCLC and 8% of breast cancer patients. Most reports of chest pain were in patients who had either a history of cardiovascular disease or tumor within the chest. There have been rare reports of myocardial infarction; however, these have not been shown definitely attributable to vinorelbine tartrate 8.

Other: Muscle weakness (asthenia) occurred in about 25% of patients with NSCLC and 41% of patients with breast cancer. It was usually mild or moderate but showed a linear increase with cumulative doses 8.

Several other toxicities reported in approximately 5% of patients include jaw pain, myalgia, arthralgia, headache, dysphagia, and skin rash. Hemorrhagic cystitis (bladder inflammation with blood in urine) and the syndrome of inappropriate ADH secretion were both reported in less than 1% of patients. The treatment of these entities are mainly symptomatic 8.

The carcinogenic potential of Vinorelbine has not been adequately studied. Vinorelbine has been demonstrated to affect chromosome number and likely the chromosome structure in vivo (polyploidy in bone marrow cells from Chinese hamsters and a positive micronucleus test in mice were observed) 8.

Affected organisms
  • Humans and other mammals
Pathways
PathwayCategory
Vinorelbine Action PathwayDrug action
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbametapirThe serum concentration of Vinorelbine can be increased when it is combined with Abametapir.
AbataceptThe metabolism of Abatacept can be increased when combined with Vinorelbine.
AbciximabThe risk or severity of bleeding can be increased when Abciximab is combined with Vinorelbine.
AcalabrutinibThe metabolism of Vinorelbine can be decreased when combined with Acalabrutinib.
AcebutololThe metabolism of Acebutolol can be decreased when combined with Vinorelbine.
AcenocoumarolThe risk or severity of bleeding can be increased when Acenocoumarol is combined with Vinorelbine.
AcetaminophenThe metabolism of Acetaminophen can be increased when combined with Vinorelbine.
AcetazolamideThe metabolism of Vinorelbine can be decreased when combined with Acetazolamide.
AcetophenazineVinorelbine may increase the neurotoxic activities of Acetophenazine.
AcetyldigitoxinAcetyldigitoxin may decrease the cardiotoxic activities of Vinorelbine.
Additional Data Available
  • Extended Description
    Extended Description

    Extended description of the mechanism of action and particular properties of each drug interaction.

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  • Severity
    Severity

    A severity rating for each drug interaction, from minor to major.

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  • Evidence Level
    Evidence Level

    A rating for the strength of the evidence supporting each drug interaction.

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  • Action
    Action

    An effect category for each drug interaction. Know how this interaction affects the subject drug.

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Food Interactions
  • Exercise caution with grapefruit products. Grapefruit inhibits CYP3A4 metabolism and may increase the serum levels of vinorelbine.
  • Exercise caution with St. John's Wort. This herb induces CYP3A4 metabolism and may reduce the serum levels of vinorelbine.

Products

Product Ingredients
IngredientUNIICASInChI Key
Vinorelbine tartrate253GQW851Q125317-39-7CILBMBUYJCWATM-KRQCOKQWSA-N
International/Other Brands
Bendarelbin (Bendalis) / Eberelbin (Ebewe) / Eunexon (AC Farma) / Eurovinorelbin (Lapharm) / Filcrin (Filaxis) / Navelbin (Pierre Fabre) / Navildez (Cryopharma) / Navin (Cancernova) / Navirel (medac) / Neocitec (Sandoz) / Renovel (Mustafa Nevzat) / Riborelbin (Ribosepharm) / Vilne (Dosa) / Vinelbine (GP-Pharm) / Vinorayne (Hospira) / Vinorel (Eriochem) / Vinorgen (Bago) / Vinotel (Fresenius) / Zinavin (Novamed)
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
NavelbineInjection10 mg/1mLIntravenousPierre Fabre Pharmaceuticals, Inc.2005-11-152021-10-31US flag
NavelbineSolutionIntravenousPierre Fabre Pharma Canada Inc1994-12-312012-10-01Canada flag
Vinorelbine InjectionSolutionIntravenousFresenius Kabi2009-03-31Not applicableCanada flag
Vinorelbine Injection, USPSolutionIntravenousGeneric Medical Partners Inc2017-08-01Not applicableCanada flag
Vinorelbine Injection, USPSolutionIntravenousMylan PharmaceuticalsNot applicableNot applicableCanada flag
Vinorelbine TartrateInjection10 mg/1mLIntravenousPierre Fabre Laboratories2005-11-152014-06-01US flag
Vinorelbine TartrateInjection10 mg/1mLIntravenousPierre Fabre Laboratories2011-08-312014-06-01US flag
Vinorelbine Tartrate for InjectionSolutionIntravenousPfizer Canada Ulc2004-12-22Not applicableCanada flag
Vinorelbine Tartrate for InjectionSolutionIntravenousTEVA Canada Limited2007-05-09Not applicableCanada flag
Vinorelbine Tartrate Injection USPSolutionIntravenousSandoz Canada IncorporatedNot applicableNot applicableCanada flag
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Aj-vinorelbineSolutionIntravenousAgila Jamp Canada IncNot applicableNot applicableCanada flag
VinorelbineInjection, solution10 mg/1mLIntravenousMylan Institutional2012-09-012016-08-31US flag
VinorelbineInjection, solution10 mg/1mLIntravenousMylan Institutional2012-09-012016-08-31US flag
VinorelbineInjection10 mg/1mLIntravenousIngenus Pharmaceuticals, LLC2019-08-08Not applicableUS flag
VinorelbineInjection, solution10 mg/1mLIntravenousPfizer Laboratories Div Pfizer Inc.2012-09-012016-08-31US flag
VinorelbineInjection, solution, concentrate10 mg/1mLIntravenousTeva Parenteral Medicines, Inc.2003-03-012012-11-30US flag
VinorelbineInjection, solution10 mg/1mLIntravenousSagent Pharmaceuticals2014-09-15Not applicableUS flag
VinorelbineInjection, solution10 mg/1mLIntravenousBedford Pharmaceuticals2004-02-112012-12-31US flag
VinorelbineInjection, solution10 mg/1mLIntravenousMylan Institutional2012-09-012016-08-31US flag
VinorelbineInjection, solution10 mg/1mLIntravenousHospira, Inc.2007-04-022019-05-31US flag
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

    Learn more
  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Categories

ATC Codes
L01CA04 — Vinorelbine
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This 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.
Kingdom
Organic compounds
Super Class
Alkaloids and derivatives
Class
Vinca alkaloids
Sub Class
Not Available
Direct Parent
Vinca alkaloids
Alternative Parents
Ibogan-type alkaloids / Carbazoles / 3-alkylindoles / Tricarboxylic acids and derivatives / Dialkylarylamines / Anisoles / Alkyl aryl ethers / Aralkylamines / N-alkylpyrrolidines / Tertiary alcohols
show 11 more
Substituents
3-alkylindole / Alcohol / Alkyl aryl ether / Amine / Amino acid or derivatives / Anisole / Aralkylamine / Aromatic heteropolycyclic compound / Azacycle / Benzenoid
show 29 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
organic heterotetracyclic compound, organic heteropentacyclic compound, acetate ester, methyl ester, vinca alkaloid (CHEBI:480999)

Chemical Identifiers

UNII
Q6C979R91Y
CAS number
71486-22-1
InChI Key
GBABOYUKABKIAF-IELIFDKJSA-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,10S,11R,12R,19R)-11-(acetyloxy)-12-ethyl-4-[(12S,14R)-16-ethyl-12-(methoxycarbonyl)-1,10-diazatetracyclo[12.3.1.0^{3,11}.0^{4,9}]octadeca-3(11),4,6,8,15-pentaen-12-yl]-10-hydroxy-5-methoxy-8-methyl-8,16-diazapentacyclo[10.6.1.0^{1,9}.0^{2,7}.0^{16,19}]nonadeca-2,4,6,13-tetraene-10-carboxylate
SMILES
[H][[email protected]@]12N(C)C3=CC(OC)=C(C=C3[[email protected]@]11CCN3CC=C[[email protected]](CC)([[email protected]@]13[H])[[email protected]@]([H])(OC(C)=O)[[email protected]]2(O)C(=O)OC)[[email protected]]1(C[[email protected]@]2([H])CN(CC(CC)=C2)CC2=C1NC1=CC=CC=C21)C(=O)OC

References

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]
  2. Piccirillo MC, Daniele G, Di Maio M, Bryce J, De Feo G, Del Giudice A, Perrone F, Morabito A: Vinorelbine for non-small cell lung cancer. Expert Opin Drug Saf. 2010 May;9(3):493-510. doi: 10.1517/14740331003774078. [PubMed:20350282]
  3. Bahadori F, Topcu G, Eroglu MS, Onyuksel H: A new lipid-based nano formulation of vinorelbine. AAPS PharmSciTech. 2014 Oct;15(5):1138-48. doi: 10.1208/s12249-014-0146-3. Epub 2014 May 29. [PubMed:24871553]
  4. Wargin WA, Lucas VS: The clinical pharmacokinetics of vinorelbine (Navelbine). Semin Oncol. 1994 Oct;21(5 Suppl 10):21-7. [PubMed:7973765]
  5. Vinorelbine Tartrate [Link]
  6. Ontario Cancer Care - Drug Formulary - vinorelbine monograph [Link]
  7. Predictors of Vinorelbine Pharmacokinetics and Pharmacodynamics in Patients With Cancer [Link]
  8. Vinorelbine injection, Daily Med [Link]
  9. Metabolism pathway of vinorelbine (Navelbine®) in human: Characterisation of the metabolites by HPLC–MS/MS [Link]
  10. Vinca Alkaloid Pharmacokinetics [Link]
  11. Vinorelbine, a clinical review [Link]
  12. Vinorelbine FDA pharmacology review [Link]
  13. Drug Approval Package [Link]
  14. Navelbine, PDR [Link]
Human Metabolome Database
HMDB0014505
KEGG Drug
D08680
PubChem Compound
44424639
PubChem Substance
46507772
ChemSpider
4470974
RxNav
39541
ChEBI
480999
ChEMBL
CHEMBL553025
ZINC
ZINC000085536958
Therapeutic Targets Database
DAP000765
PharmGKB
PA451881
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Vinorelbine
AHFS Codes
  • 10:00.00 — Antineoplastic Agents
FDA label
Download (102 KB)
MSDS
Download (155 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4CompletedTreatmentBreast Cancer1
4CompletedTreatmentMetastatic Non-Small Cell Lung Cancer1
4CompletedTreatmentNon-Small Cell Lung Carcinoma (NSCLC)2
4RecruitingTreatmentMetastatic Breast Cancer1
4RecruitingTreatmentPrimary Breast Cancer1
3Active Not RecruitingTreatmentBreast Cancer2
3Active Not RecruitingTreatmentHER2 Positive Breast Cancers / Neoplasms, Metastatic1
3Active Not RecruitingTreatmentHER2-positive Locally Advanced or Metastatic Breast Cancer1
3Active Not RecruitingTreatmentLung Cancers1
3Active Not RecruitingTreatmentMetastatic Breast Cancer1

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
  • APP Pharmaceuticals
  • Bedford Labs
  • Ben Venue Laboratories Inc.
  • Ebewe Pharma
  • Hospira Inc.
  • Pierre Fabre
  • Sagent Pharmaceuticals
  • Sicor Pharmaceuticals
  • Teva Pharmaceutical Industries Ltd.
  • Wyeth Pharmaceuticals
Dosage Forms
FormRouteStrength
SolutionParenteral10 mg/ml
Capsule
CapsuleOral20 MG
CapsuleOral30 MG
CapsuleOral40 MG
CapsuleOral80 MG
Injection, solution, concentrateIntravenous10 MG/ML
SolutionParenteral10 mg
Injection10 mg/1ml
CapsuleOral
SolutionParenteral40 mg
SolutionParenteral50 mg
Solution, concentrateIntravenous50 mg
Injection50 mg/5ml
Injection
Capsule, liquid filledOral20 mg
Capsule, liquid filledOral30 mg
Injection, solution50 mg/5ml
Injection, solution, concentrateIntravenous; Parenteral10 MG/ML
Capsule20 MG
Capsule30 MG
Capsule80 MG
SolutionIntravenous50 mg
InjectionIntravenous50 mg/5mL
Injection, solution, concentrateIntravenous10 mg/1mL
Injection, solution, concentrateIntravenous50 mg/5mL
InjectionIntravenous10 mg/1mL
Injection, solutionIntravenous10 mg/1mL
SolutionIntravenous
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.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)181-183MSDS
water solubility10 mg/mL in waterMSDS
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)8.66ChemAxon
Physiological Charge2ChemAxon
Hydrogen Acceptor Count8ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area133.87 Å2ChemAxon
Rotatable Bond Count10ChemAxon
Refractivity216.99 m3·mol-1ChemAxon
Polarizability84.31 Å3ChemAxon
Number of Rings9ChemAxon
Bioavailability1ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
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)

Spectra

Mass Spec (NIST)
Not Available
Spectra
Not Available

Targets

Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Antagonist
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
Uniprot Name
Tubulin beta chain
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
Humans
Pharmacological action
Yes
Actions
Substrate
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 react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Leveque D, Wisniewski S, Renault C, Peter JD, Le Corre P, Monteil H, Jehl F: The effect of rifampin on the pharmacokinetics of vinorelbine in the micropig. Anticancer Res. 2003 May-Jun;23(3B):2741-4. [PubMed:12894568]
  2. Beulz-Riche D, Grude P, Puozzo C, Sautel F, Filaquier C, Riche C, Ratanasavanh D: Characterization of human cytochrome P450 isoenzymes involved in the metabolism of vinorelbine. Fundam Clin Pharmacol. 2005 Oct;19(5):545-53. doi: 10.1111/j.1472-8206.2005.00367.x. [PubMed:16176333]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
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...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 Da
References
  1. Le Guellec C, Lacarelle B, Catalin J, Durand A: Inhibitory effects of anticancer drugs on dextromethorphan-O-demethylase activity in human liver microsomes. Cancer Chemother Pharmacol. 1993;32(6):491-5. [PubMed:8258200]

Drug created on June 13, 2005 07:24 / Updated on October 21, 2020 01:55

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