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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
Prescription ProductsNot Available
Generic Prescription ProductsNot Available
Over the Counter ProductsNot Available
International Brands
NameCompany
EldesineNot Available
EldisineNot Available
Brand mixturesNot Available
Salts
Name/CASStructureProperties
Vindesine Sulfate
59917-39-4
Thumb
  • InChI Key: COFJBSXICYYSKG-FJFFLIEUSA-N
  • Monoisotopic Mass: 851.377528381
  • Average Mass: 852.005
DBSALT000440
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[10.6.1.0¹,⁹.0²,⁷.0¹⁶,¹⁹]nonadeca-2,4,6,13-tetraen-4-yl]-17-ethyl-17-hydroxy-1,11-diazatetracyclo[13.3.1.0⁴,¹².0⁵,¹⁰]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
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
  • Quinoline-6-carboxamide
  • Carbazole
  • Indole or derivatives
  • Indole
  • Dialkylarylamine
  • Anisole
  • Aralkylamine
  • Tetrahydropyridine
  • Alkyl aryl ether
  • Benzenoid
  • N-alkylpyrrolidine
  • Piperidine
  • Heteroaromatic compound
  • Methyl ester
  • Tertiary alcohol
  • Pyrrolidine
  • Pyrrole
  • Cyclic alcohol
  • Tertiary aliphatic amine
  • Tertiary amine
  • Secondary alcohol
  • Primary carboxylic acid amide
  • Carboxylic acid ester
  • Carboxamide group
  • 1,2-diol
  • 1,2-aminoalcohol
  • Azacycle
  • Organoheterocyclic compound
  • Monocarboxylic acid or derivatives
  • Ether
  • Carboxylic acid derivative
  • Carboxylic acid amide
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Amine
  • Alcohol
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
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
PropertyValueProbability
Human Intestinal Absorption+0.9027
Blood Brain Barrier-0.9821
Caco-2 permeable-0.5154
P-glycoprotein substrateSubstrate0.9164
P-glycoprotein inhibitor INon-inhibitor0.5717
P-glycoprotein inhibitor IINon-inhibitor0.6577
Renal organic cation transporterNon-inhibitor0.8851
CYP450 2C9 substrateNon-substrate0.8468
CYP450 2D6 substrateNon-substrate0.9116
CYP450 3A4 substrateSubstrate0.7597
CYP450 1A2 substrateNon-inhibitor0.8766
CYP450 2C9 substrateNon-inhibitor0.8798
CYP450 2D6 substrateNon-inhibitor0.8911
CYP450 2C19 substrateNon-inhibitor0.8814
CYP450 3A4 substrateNon-inhibitor0.811
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.933
Ames testNon AMES toxic0.8682
CarcinogenicityNon-carcinogens0.8976
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.9430 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9892
hERG inhibition (predictor II)Inhibitor0.6584
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point230-232 °CNot Available
logP2.9Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.07 mg/mLALOGPS
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 FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
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
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