Banner
targets (1) enzymes (1)
for drugs
Identification
Name Vindesine
Accession Number DB00309 (APRD00392)
Type small molecule
Groups approved
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
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
Desacetylvinblastine Amide Sulfate
Vindesine Sulfate
Salts Not Available
Brand names
Name Company
DAVA
Eldesine
Eldisine
Brand mixtures Not Available
Categories
  • Antineoplastic Agents
  • Antineoplastic Agents, Phytogenic
  • Tubulin Modulators
CAS number 59917-39-4
Weight Average: 753.9261
Monoisotopic: 753.410149139
Chemical Formula C43H55N5O7
InChI Key InChIKey=HHJUWIANJFBDHT-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
Plain Text
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
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Tryptamines and Derivatives
Substructures
  • Carbonyl Compounds
  • Carboxylic Acids and Derivatives
  • Hydroxy Compounds
  • Alkanes and Alkenes
  • Acetates
  • Indoles and Indole Derivatives
  • Phenols and Derivatives
  • Amino Ketones
  • Aliphatic and Aryl Amines
  • Pyrroles
  • Phenylacetates
  • Pyrrolidines
  • Ethers
  • Benzene and Derivatives
  • Carbamates and Derivatives
  • Alcohols and Polyols
  • Phenethylamines
  • Heterocyclic compounds
  • Aromatic compounds
  • Anisoles
  • Carboxamides and Derivatives
  • Phenylpropylamines
  • Tryptamines and Derivatives
  • Imines
  • Phenyl Esters
  • Anilines
  • Amphetamines
  • Piperidines
  • Pyrrolines
Pharmacology
Indication For the treatment of acute leukaemia, malignant lymphoma, Hodgkin's disease, acute erythraemia and acute panmyelosis
Pharmacodynamics Vindesine 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 action Vindesine 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.
Absorption Not Available
Volume of distribution Not Available
Protein binding 65-75%
Metabolism Hepatic
Route of elimination Not Available
Half life 24 hours.
Clearance Not Available
Toxicity Not Available
Affected organisms
  • Humans and other mammals
Pathways
Pathway Name SMPDB ID
Smp00438 Vindesine Pathway SMP00438
Pharmacoeconomics
Manufacturers Not Available
Packagers Not Available
Dosage forms
Form Route Strength
Solution Intravenous
Prices Not Available
Patents Not Available
Properties
State solid
Experimental Properties
Property Value Source
melting point 230-232 °C Not Available
logP 2.9 Not Available
Predicted Properties
Property Value Source
water solubility 7.00e-02 g/l ALOGPS
logP 3.53 ALOGPS
logP 2.79 ChemAxon
logS -4 ALOGPS
pKa (strongest acidic) 11.34 ChemAxon
pKa (strongest basic) 8.68 ChemAxon
physiological charge 2 ChemAxon
hydrogen acceptor count 9 ChemAxon
hydrogen donor count 5 ChemAxon
polar surface area 164.82 ChemAxon
rotatable bond count 7 ChemAxon
refractivity 210.32 ChemAxon
polarizability 82.58 ChemAxon
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
KEGG Drug D01769 Link_out
PubChem Compound 40839 Link_out
PubChem Substance 46504548 Link_out
ChemSpider 37302 Link_out
ChEBI 36373 Link_out
ChEMBL 36373 Link_out
Therapeutic Targets Database DAP000949 Link_out
PharmGKB PA10232 Link_out
Drug Product Database 555665 Link_out
RxList http://www.rxlist.com/cgi/generic2/vinor_cp.htm Link_out
Wikipedia http://en.wikipedia.org/wiki/Vindesine Link_out
ATC Codes
  • L01CA03
AHFS Codes Not Available
PDB Entries Not Available
FDA label Not Available
MSDS Not Available
Interactions
Drug Interactions
Drug Interaction
Mitomycin Potentially severe lung toxicity
Quinupristin This combination presents an increased risk of toxicity
Food Interactions Not Available
Targets

1. Tubulin beta-1 chain

Pharmacological action: yes
Actions: inhibitor

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

Organism class: human
UniProt ID: Q9H4B7 Link_out
Gene: TUBB1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Actions: substrate

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 reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4- hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. The enzyme also hydroxylates etoposide

UniProt ID: P08684 Link_out
Gene: CYP3A4
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
Comments
Drug created on June 13, 2005 07:24 / Updated on February 08, 2013 16:19