Vinorelbine
Identification
- Summary
Vinorelbine is a vinca alkaloid used in the treatment of metastatic non-small cell lung carcinoma (NSLC) and in conjunction with other drugs in locally advanced NSCLC.
- Generic Name
- Vinorelbine
- DrugBank Accession Number
- DB00361
- Background
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
- 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.
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Used in combination to treat Locally advanced non-small cell lung cancer Regimen in combination with: Cisplatin (DB00515) •••••••••••• •••••••••• ••••••••• Treatment of Metastatic breast cancer ••• ••••• Treatment of Metastatic cervical cancer ••• ••••• Used in combination to treat Metastatic non-small cell lung cancer Regimen in combination with: Cisplatin (DB00515) •••••••••••• •••••••••• ••••••••• Treatment of Metastatic non-small cell lung cancer •••••••••••• ••••••••••• - 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.
Target Actions Organism ATubulin beta chain antagonistinhibitorHumans - 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.
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- 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.
- Pathways
Pathway Category Vinorelbine Action Pathway Drug action - Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
- Not Available
Interactions
- Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
- 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.
Drug Interaction Integrate drug-drug
interactions in your softwareAbametapir The serum concentration of Vinorelbine can be increased when it is combined with Abametapir. Abatacept The metabolism of Vinorelbine can be increased when combined with Abatacept. Abciximab The risk or severity of bleeding can be increased when Abciximab is combined with Vinorelbine. Acalabrutinib The metabolism of Vinorelbine can be decreased when combined with Acalabrutinib. Acebutolol The metabolism of Acebutolol can be decreased when combined with Vinorelbine. - 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
- Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.
- Product Ingredients
Ingredient UNII CAS InChI Key Vinorelbine tartrate 253GQW851Q 125317-39-7 CILBMBUYJCWATM-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
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Navelbine Injection 10 mg/1mL Intravenous Pierre Fabre Pharmaceuticals, Inc. 2005-11-15 2021-10-31 US Navelbine Solution 10 mg / mL Intravenous Pierre Fabre Pharma Canada Inc 1994-12-31 2012-10-01 Canada Vinorelbine Injection Solution 10 mg / mL Intravenous Fresenius Kabi 2009-03-31 2021-07-20 Canada Vinorelbine Injection, USP Solution 10 mg / mL Intravenous Generic Medical Partners Inc 2017-08-01 Not applicable Canada Vinorelbine Injection, USP Solution 10 mg / mL Intravenous Mylan Pharmaceuticals Not applicable Not applicable Canada - Generic Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Aj-vinorelbine Solution 10 mg / mL Intravenous Agila Jamp Canada Inc Not applicable Not applicable Canada Vinorelbine Injection, solution 10 mg/1mL Intravenous Actavis Pharma, Inc. 2015-03-01 Not applicable US Vinorelbine Injection 10 mg/1mL Intravenous Ingenus Pharmaceuticals, LLC 2019-08-08 Not applicable US Vinorelbine Injection, solution, concentrate 10 mg/1mL Intravenous Teva Parenteral Medicines, Inc. 2003-03-01 2012-11-30 US Vinorelbine Injection, solution 10 mg/1mL Intravenous Sagent Pharmaceuticals 2014-09-15 Not applicable US
Categories
- ATC Codes
- L01CA04 — Vinorelbine
- Drug Categories
- Alkaloids
- Antimitotic Agents
- Antineoplastic Agents
- Antineoplastic Agents, Phytogenic
- Antineoplastic and Immunomodulating Agents
- Cardiotoxic antineoplastic agents
- Cytochrome P-450 CYP2D6 Inhibitors
- Cytochrome P-450 CYP2D6 Inhibitors (weak)
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 CYP3A4 Substrates with a Narrow Therapeutic Index
- Cytochrome P-450 Enzyme Inhibitors
- Cytochrome P-450 Substrates
- Heterocyclic Compounds, Fused-Ring
- Immunosuppressive Agents
- Indole Alkaloids
- Indoles
- Indolizidines
- Indolizines
- Mitosis Modulators
- Myelosuppressive Agents
- Narrow Therapeutic Index Drugs
- Neurotoxic agents
- Secologanin Tryptamine Alkaloids
- Tubulin Modulators
- Vinca Alkaloids
- 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)
- Affected organisms
- Humans and other mammals
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][C@@]12N(C)C3=CC(OC)=C(C=C3[C@@]11CCN3CC=C[C@](CC)([C@@]13[H])[C@@]([H])(OC(C)=O)[C@]2(O)C(=O)OC)[C@]1(C[C@@]2([H])CN(CC(CC)=C2)CC2=C1NC1=CC=CC=C21)C(=O)OC
References
- General References
- 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. [Article]
- 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. [Article]
- 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. [Article]
- Wargin WA, Lucas VS: The clinical pharmacokinetics of vinorelbine (Navelbine). Semin Oncol. 1994 Oct;21(5 Suppl 10):21-7. [Article]
- Vinorelbine Tartrate [Link]
- Ontario Cancer Care - Drug Formulary - vinorelbine monograph [Link]
- Predictors of Vinorelbine Pharmacokinetics and Pharmacodynamics in Patients With Cancer [Link]
- Vinorelbine injection, Daily Med [Link]
- Metabolism pathway of vinorelbine (Navelbine®) in human: Characterisation of the metabolites by HPLC–MS/MS [Link]
- Vinca Alkaloid Pharmacokinetics [Link]
- Vinorelbine, a clinical review [Link]
- Vinorelbine FDA pharmacology review [Link]
- Drug Approval Package [Link]
- Navelbine, PDR [Link]
- External Links
- Human Metabolome Database
- HMDB0014505
- KEGG Drug
- D08680
- PubChem Compound
- 44424639
- PubChem Substance
- 46507772
- ChemSpider
- 4470974
- 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
- FDA label
- Download (102 KB)
- MSDS
- Download (155 KB)
Clinical Trials
- Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count 4 Completed Treatment Breast Cancer 1 4 Completed Treatment Metastatic Non-Small Cell Lung Cancer 1 4 Completed Treatment Non-Small Cell Lung Cancer (NSCLC) 2 4 Recruiting Treatment Metastatic Breast Cancer 2 4 Recruiting Treatment Non-Small Cell Lung Cancer (NSCLC) 1
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
Form Route Strength Solution Intravenous 13.85 mg Injection, solution, concentrate Intravenous 10 mg/ml Solution Parenteral 10 mg/ml Capsule Oral Capsule Oral 200 mg Capsule Oral 40 MG Capsule Oral 80 MG Injection Intravenous Solution Parenteral Capsule Oral 20 mg Capsule Oral 30 mg Solution, concentrate Intravenous 50 mg Injection, solution Intravenous 50 mg/5ml Injection Intravenous 10 mg/ml Capsule, liquid filled Oral 20 mg Capsule, liquid filled Oral 30 mg Solution Parenteral 10.000 mg Capsule Oral 20.000 mg Capsule Oral 27.700 mg Injection, solution Intravenous Injection, solution Intravenous 10 MG/ML Injection, solution, concentrate Intravenous; Parenteral 10 MG/ML Injection, solution, concentrate Intravenous Solution Intravenous 50 mg Injection Intravenous 50 mg/5mL Injection, solution, concentrate Intravenous 10 mg/1mL Injection, solution, concentrate Intravenous 50 mg/5mL Capsule, liquid filled Oral 20.00 mg Capsule, liquid filled Oral 30.00 mg Injection Intravenous 10 mg/1mL Injection, solution Intravenous 10 mg/1mL Solution Intravenous 10 mg / mL Solution 10 mg/1ml - Prices
Unit description Cost Unit Navelbine 50 mg/5 ml vial 42.0USD ml Vinorelbine 50 mg/5 ml vial 27.6USD ml DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 181-183 MSDS water solubility 10 mg/mL in water MSDS logP 4 Not Available - Predicted Properties
Property Value Source Water Solubility 0.0122 mg/mL ALOGPS logP 4.39 ALOGPS logP 4.65 Chemaxon logS -4.8 ALOGPS pKa (Strongest Acidic) 10.87 Chemaxon pKa (Strongest Basic) 8.66 Chemaxon Physiological Charge 2 Chemaxon Hydrogen Acceptor Count 8 Chemaxon Hydrogen Donor Count 2 Chemaxon Polar Surface Area 133.87 Å2 Chemaxon Rotatable Bond Count 10 Chemaxon Refractivity 216.99 m3·mol-1 Chemaxon Polarizability 84.31 Å3 Chemaxon Number of Rings 9 Chemaxon Bioavailability 1 Chemaxon Rule of Five No Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule Yes Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.974 Blood Brain Barrier - 0.8815 Caco-2 permeable + 0.5602 P-glycoprotein substrate Substrate 0.9283 P-glycoprotein inhibitor I Inhibitor 0.7488 P-glycoprotein inhibitor II Inhibitor 0.7388 Renal organic cation transporter Non-inhibitor 0.6979 CYP450 2C9 substrate Non-substrate 0.8513 CYP450 2D6 substrate Substrate 0.6471 CYP450 3A4 substrate Substrate 0.7247 CYP450 1A2 substrate Non-inhibitor 0.8415 CYP450 2C9 inhibitor Non-inhibitor 0.7863 CYP450 2D6 inhibitor Non-inhibitor 0.8369 CYP450 2C19 inhibitor Non-inhibitor 0.8381 CYP450 3A4 inhibitor Non-inhibitor 0.8095 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.6672 Ames test Non AMES toxic 0.8064 Carcinogenicity Non-carcinogens 0.9299 Biodegradation Not ready biodegradable 1.0 Rat acute toxicity 2.8350 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9014 hERG inhibition (predictor II) Non-inhibitor 0.5171
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Not Available
Targets
![](https://go.drugbank.com/assets/locked/DrugTargets2-682eb846d210ae4bf33ca03febccfb57bb1c61318e699b729e5df4dfab2c5b67.png)
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- AntagonistInhibitor
- 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
- Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- 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
- 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. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- 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
- 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. [Article]
- 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. [Article]
Drug created at June 13, 2005 13:24 / Updated at February 20, 2024 23:54