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Identification
NameVindesine
Accession NumberDB00309  (APRD00392)
TypeSmall Molecule
GroupsApproved
Description

Vinblastine derivative with antineoplastic activity against cancer. Major side effects are myelosuppression and neurotoxicity. Vindesine is used extensively in chemotherapy protocols (antineoplastic combined chemotherapy protocols). [PubChem]

Structure
Thumb
Synonyms
SynonymLanguageCode
3-(Aminocarbonyl)-O(4)-deacetyl-3-de(methoxycarbonyl)vincaleukoblastineNot AvailableNot Available
3-Carbamoyl-4-deacetyl-3-de(methoxycarbonyl)vincaleukoblastineNot AvailableNot Available
Desacetylvinblastine amideNot AvailableNot Available
Salts
Name/CAS Structure Properties
Vindesine Sulfate
59917-39-4
Thumb
  • InChI Key: COFJBSXICYYSKG-FJFFLIEUSA-N
  • Monoisotopic Mass: 851.377528381
  • Average Mass: 852.005
DBSALT000440
Brand names
NameCompany
EldesineNot Available
EldisineNot Available
Brand mixturesNot Available
Categories
CAS number53643-48-4
WeightAverage: 753.9261
Monoisotopic: 753.410149139
Chemical FormulaC43H55N5O7
InChI KeyHHJUWIANJFBDHT-KOTLKJBCSA-N
InChI
InChI=1S/C43H55N5O7/c1-6-39(52)21-25-22-42(38(51)55-5,33-27(13-17-47(23-25)24-39)26-11-8-9-12-30(26)45-33)29-19-28-31(20-32(29)54-4)46(3)35-41(28)15-18-48-16-10-14-40(7-2,34(41)48)36(49)43(35,53)37(44)50/h8-12,14,19-20,25,34-36,45,49,52-53H,6-7,13,15-18,21-24H2,1-5H3,(H2,44,50)/t25-,34+,35-,36-,39+,40-,41-,42+,43+/m1/s1
IUPAC Name
methyl (13S,15S,17S)-13-[(1R,9R,10S,11R,12R,19R)-10-carbamoyl-12-ethyl-10,11-dihydroxy-5-methoxy-8-methyl-8,16-diazapentacyclo[10.6.1.0^{1,9}.0^{2,7}.0^{16,19}]nonadeca-2(7),3,5,13-tetraen-4-yl]-17-ethyl-17-hydroxy-1,11-diazatetracyclo[13.3.1.0^{4,12}.0^{5,10}]nonadeca-4(12),5,7,9-tetraene-13-carboxylate
SMILES
[H][C@@]12N3CC[C@@]11C4=CC(=C(OC)C=C4N(C)[C@@]1([H])[C@](O)([C@H](O)[C@]2(CC)C=CC3)C(N)=O)[C@]1(C[C@]2([H])CN(C[C@](O)(CC)C2)CCC2=C1NC1=CC=CC=C21)C(=O)OC
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassAlkaloids and Derivatives
ClassRhazinilam Alkaloids
SubclassNot Available
Direct parentRhazinilam Alkaloids
Alternative parentsPlumeran-type Alkaloids; Quinoline Carboxamides; Carbazoles; Indoles; Anisoles; Cyclohexanols; Alkyl Aryl Ethers; Tetrahydropyridines; Piperidines; Pyrrolidines; Tertiary Alcohols; Pyrroles; Tertiary Amines; Cyclic Alcohols and Derivatives; Primary Carboxylic Acid Amides; Carboxylic Acid Esters; 1,2-Diols; Carboxylic Acids; Enolates; Polyamines
Substituentscarbazole; quinoline-6-carboxamide; indole or derivative; indole; phenol ether; anisole; cyclohexanol; tetrahydropyridine; alkyl aryl ether; piperidine; benzene; cyclic alcohol; pyrrole; tertiary alcohol; pyrrolidine; 1,2-diol; tertiary amine; primary carboxylic acid amide; carboxylic acid ester; carboxamide group; secondary alcohol; polyamine; carboxylic acid derivative; carboxylic acid; ether; enolate; alcohol; organonitrogen compound; amine
Classification descriptionThis compound belongs to the rhazinilam alkaloids.
Pharmacology
IndicationFor the treatment of acute leukaemia, malignant lymphoma, Hodgkin's disease, acute erythraemia and acute panmyelosis
PharmacodynamicsVindesine is indicated for the treatment of acute lymphocytic leukemia of childhood that is resistant to vincristine and non-oat cell lung cancer.Vindesine causes the arrest of cells in metaphase mitosis. It is three times more potent than vincristine and nearly 10 times more potent than vinblastine in causing mitotic arrest in in vitro studies at doses designed to arrest from 10 to 15% of the cells in mitosis. Vindesine and vincristine are approximately equipotent at dose levels that arrest 40 to 50% of the cells in mitosis. Unlike vinblastine, vindesine produces very few postmetaphase cells. Vindesine has demonstrated activity in patients who have relapsed while receiving multiple-agent treatment that included vincristine.
Mechanism of actionVindesine acts by causing the arrest of cells in metaphase mitosis through its inhibition tubulin mitotic funcitoning. The drug is cell-cycle specific for the S phase.
AbsorptionNot Available
Volume of distributionNot Available
Protein binding65-75%
Metabolism

Hepatic

SubstrateEnzymesProduct
Vindesine
UnknownDetails
Route of eliminationNot Available
Half life24 hours.
ClearanceNot Available
ToxicityNot Available
Affected organisms
  • Humans and other mammals
Pathways
PathwayCategorySMPDB ID
Vindesine Action PathwayDrug actionSMP00438
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 0.9027
Blood Brain Barrier - 0.9821
Caco-2 permeable - 0.5154
P-glycoprotein substrate Substrate 0.9164
P-glycoprotein inhibitor I Non-inhibitor 0.5717
P-glycoprotein inhibitor II Non-inhibitor 0.6577
Renal organic cation transporter Non-inhibitor 0.8851
CYP450 2C9 substrate Non-substrate 0.8468
CYP450 2D6 substrate Non-substrate 0.9116
CYP450 3A4 substrate Substrate 0.7597
CYP450 1A2 substrate Non-inhibitor 0.8766
CYP450 2C9 substrate Non-inhibitor 0.8798
CYP450 2D6 substrate Non-inhibitor 0.8911
CYP450 2C19 substrate Non-inhibitor 0.8814
CYP450 3A4 substrate Non-inhibitor 0.811
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.933
Ames test Non AMES toxic 0.8682
Carcinogenicity Non-carcinogens 0.8976
Biodegradation Not ready biodegradable 1.0
Rat acute toxicity 2.9430 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.9892
hERG inhibition (predictor II) Inhibitor 0.6584
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage forms
FormRouteStrength
SolutionIntravenous
PricesNot Available
PatentsNot Available
Properties
Statesolid
Experimental Properties
PropertyValueSource
melting point230-232 °CNot Available
logP2.9Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.07ALOGPS
logP3.53ALOGPS
logP2.79ChemAxon
logS-4ALOGPS
pKa (Strongest Acidic)11.34ChemAxon
pKa (Strongest Basic)8.68ChemAxon
Physiological Charge2ChemAxon
Hydrogen Acceptor Count9ChemAxon
Hydrogen Donor Count5ChemAxon
Polar Surface Area164.82 Å2ChemAxon
Rotatable Bond Count7ChemAxon
Refractivity210.32 m3·mol-1ChemAxon
Polarizability82.58 Å3ChemAxon
Number of Rings9ChemAxon
Bioavailability1ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Spectra
SpectraNot Available
References
Synthesis Reference

Stanislaw Rolski, “Method of preparing vindesine sulfate.” U.S. Patent US4259242, issued September, 1965.

US4259242
General ReferenceNot Available
External Links
ResourceLink
KEGG DrugD01769
PubChem Compound40839
PubChem Substance46504548
ChemSpider37302
ChEBI36373
ChEMBLCHEMBL219146
Therapeutic Targets DatabaseDAP000949
PharmGKBPA10232
Drug Product Database555665
RxListhttp://www.rxlist.com/cgi/generic2/vinor_cp.htm
WikipediaVindesine
ATC CodesL01CA03
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug Interactions
Drug
MitomycinPotentially severe lung toxicity
QuinupristinThis combination presents an increased risk of toxicity
Food InteractionsNot Available

Targets

1. Tubulin beta-1 chain

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Tubulin beta-1 chain Q9H4B7 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. Natsume T, Watanabe J, Tamaoki S, Fujio N, Miyasaka K, Kobayashi M: Characterization of the interaction of TZT-1027, a potent antitumor agent, with tubulin. Jpn J Cancer Res. 2000 Jul;91(7):737-47. Pubmed
  4. Yoshida M, Matsui Y, Ikarashi Y, Usui T, Osada H, Wakasugi H: Antiproliferating activity of the mitotic inhibitor pironetin against vindesine- and paclitaxel-resistant human small cell lung cancer H69 cells. Anticancer Res. 2007 Mar-Apr;27(2):729-36. Pubmed
  5. Fiebig HH, Schuler J, Bausch N, Hofmann M, Metz T, Korrat A: Gene signatures developed from patient tumor explants grown in nude mice to predict tumor response to 11 cytotoxic drugs. Cancer Genomics Proteomics. 2007 May-Jun;4(3):197-209. Pubmed

Enzymes

1. Cytochrome P450 3A4

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

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. Ekins S, Bravi G, Wikel JH, Wrighton SA: Three-dimensional-quantitative structure activity relationship analysis of cytochrome P-450 3A4 substrates. J Pharmacol Exp Ther. 1999 Oct;291(1):424-33. Pubmed

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Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:09