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Record Information
Version2.0
Creation Date2014-08-29 04:49:14 UTC
Update Date2014-12-24 20:26:35 UTC
Accession NumberT3D4016
Identification
Common NameVincristine
ClassSmall Molecule
DescriptionVincristine is only found in individuals that have used or taken this drug. It is an antitumor alkaloid isolated from Vinca Rosea. (Merck, 11th ed.) The antitumor activity of Vincristine is thought to be due primarily to inhibition of mitosis at metaphase through its interaction with tubulin. Like other vinca alkaloids, Vincristine may also interfere with: 1) amino acid, cyclic AMP, and glutathione metabolism, 2) calmodulin-dependent Ca2+-transport ATPase activity, 3) cellular respiration, and 4) nucleic acid and lipid biosynthesis. Vincristine is indicated for the treatment of acute leukaemia, malignant lymphoma, Hodgkin's disease, acute erythraemia, and acute panmyelosis. Vincristine sulfate is often chosen as part of polychemotherapy because of lack of significant bone marrow suppression (at recommended doses) and of unique clinical toxicity (neuropathy).
Compound Type
  • Amide
  • Amine
  • Antineoplastic Agent, Phytogenic
  • Drug
  • Ester
  • Ether
  • Metabolite
  • Organic Compound
  • Synthetic Compound
  • Tubulin Modulator
Chemical Structure
Thumb
Synonyms
Synonym
22-Oxovincaleukoblastin
22-Oxovincaleukoblastine
Alcavixin
Alcrist
Citomid
Cytocristin
Indole alkaloid
LCR
Leurocristine
Marqibo
Oncocristin
Oncovin
Oncrivin
Sindovin
Tevacristin
VCR
VIN
Vinces
Vincrisin
Vincristin
Vincristina
Vincristinum
Vincrisul
Vincrstine
Vincrystine
Vinlon
Vinracine
Z-D-Val-Lys(Z)-OH
Chemical FormulaC46H56N4O10
Average Molecular Mass824.958 g/mol
Monoisotopic Mass824.400 g/mol
CAS Registry Number57-22-7
IUPAC Namemethyl (1R,9R,10S,11R,12R,19R)-11-(acetyloxy)-12-ethyl-4-[(13S,15S,17S)-17-ethyl-17-hydroxy-13-(methoxycarbonyl)-1,11-diazatetracyclo[13.3.1.0⁴,¹².0⁵,¹⁰]nonadeca-4(12),5,7,9-tetraen-13-yl]-8-formyl-10-hydroxy-5-methoxy-8,16-diazapentacyclo[10.6.1.0¹,⁹.0²,⁷.0¹⁶,¹⁹]nonadeca-2,4,6,13-tetraene-10-carboxylate
Traditional Namevincristine
SMILES[H][C@@]12N3CC[C@@]11C4=CC(=C(OC)C=C4N(C=O)[C@@]1([H])[C@@](O)(C(=O)OC)[C@]([H])(OC(C)=O)[C@]2(CC)C=CC3)[C@]1(C[C@]2([H])CN(C[C@](O)(CC)C2)CCC2=C1NC1=CC=CC=C21)C(=O)OC
InChI IdentifierInChI=1S/C46H56N4O10/c1-7-42(55)22-28-23-45(40(53)58-5,36-30(14-18-48(24-28)25-42)29-12-9-10-13-33(29)47-36)32-20-31-34(21-35(32)57-4)50(26-51)38-44(31)16-19-49-17-11-15-43(8-2,37(44)49)39(60-27(3)52)46(38,56)41(54)59-6/h9-13,15,20-21,26,28,37-39,47,55-56H,7-8,14,16-19,22-25H2,1-6H3/t28-,37+,38-,39-,42+,43-,44-,45+,46+/m1/s1
InChI KeyInChIKey=OGWKCGZFUXNPDA-XQKSVPLYSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as dipeptides. These are organic compounds containing a sequence of exactly two alpha-amino acids joined by a peptide bond.
KingdomOrganic compounds
Super ClassOrganic acids and derivatives
ClassCarboxylic acids and derivatives
Sub ClassAmino acids, peptides, and analogues
Direct ParentDipeptides
Alternative Parents
Substituents
  • Alpha-dipeptide
  • Alpha-amino acid ester
  • Benzazepine
  • Alpha-amino acid or derivatives
  • Azepine
  • Fatty acid ester
  • Aralkylamine
  • Dicarboxylic acid or derivatives
  • Monocyclic benzene moiety
  • Fatty acyl
  • Benzenoid
  • Tertiary carboxylic acid amide
  • Carboxylic acid ester
  • Amino acid or derivatives
  • Amino acid
  • Lactam
  • Carboxamide group
  • Carboxylic acid
  • Secondary aliphatic amine
  • Azacycle
  • Secondary amine
  • Organoheterocyclic compound
  • Organic nitrogen compound
  • Organonitrogen compound
  • Carbonyl group
  • Organooxygen compound
  • Hydrocarbon derivative
  • Organic oxide
  • Organopnictogen compound
  • Amine
  • Organic oxygen compound
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Cytoplasm
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
Pathways
NameSMPDB LinkKEGG Link
Vincristine PathwayNot AvailableNot Available
ApplicationsNot Available
Biological Roles
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point220°C
Boiling PointNot Available
Solubility3.00e-02 g/L
LogP2.82
Predicted Properties
PropertyValueSource
Water Solubility0.03 g/LALOGPS
logP3.36ALOGPS
logP3.13ChemAxon
logS-4.4ALOGPS
pKa (Strongest Acidic)10.85ChemAxon
pKa (Strongest Basic)8.66ChemAxon
Physiological Charge2ChemAxon
Hydrogen Acceptor Count9ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area171.17 ŲChemAxon
Rotatable Bond Count10ChemAxon
Refractivity221.48 m³·mol⁻¹ChemAxon
Polarizability88.59 ųChemAxon
Number of Rings9ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyView
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-05r0-0000000960-3a843563d341d8bc8c67JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-05ot-0000000910-19f858ef585f6c37c067JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0537-1200000900-8774d71fd76cf13c57feJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0c00-2005000950-4682841abaeccf6ff250JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-052r-1009000100-ce5fe6558a0993ae42c6JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0a4i-9002300800-16d21458a9981b9e680cJSpectraViewer
MSMass Spectrum (Electron Ionization)splash10-07e3-5000006910-b246ba0d2babb32fc98eJSpectraViewer | MoNA
Toxicity Profile
Route of ExposureNot Available
Mechanism of ToxicityThe antitumor activity of Vincristine is thought to be due primarily to inhibition of mitosis at metaphase through its interaction with tubulin. Like other vinca alkaloids, Vincristine may also interfere with: 1) amino acid, cyclic AMP, and glutathione metabolism, 2) calmodulin-dependent Ca2+-transport ATPase activity, 3) cellular respiration, and 4) nucleic acid and lipid biosynthesis.
MetabolismHepatic. Cytochrome P450 isoenzymes of the CYP3A subfamily facilitate the metabolism of vincristine. Route of Elimination: The liver is the major excretory organ in humans and animals. 80% of an injected dose of vincristine sulfate is excreted via feces. 10 - 20% is excreted via urine. Half Life: When intravenously injected into cancer patients, a triphasic serum decay patten was observed. The initial, middle, and terminal half-lives are 5 minutes, 2.3 hours, 85 hours respectively. The range of the terminal half-life is humans is 19 - 155 hours.
Toxicity ValuesIVN-RAT LD50 1300 mg/kg; IPR-MUS LD50 5.2 mg/kg.
Lethal DoseNot Available
Carcinogenicity (IARC Classification)Vincristine sulfate is not classifiable as to its carcinogenicity to humans (Group 3). Vincristine is part of MOPP, a combination chemotherapy regimen that is carcinogenic to humans (Group 1). (6)
Uses/SourcesTreatment of acute lymphocytic leukemia (ALL), Hodgkin lymphoma, non-Hodgkin lymphomas, Wilms' tumor, neuroblastoma, rhabdomyosarcoma. Liposomal vincristine is indicated for the treatment of relapsed Philadelphia chromosome-negative (Ph-) acute lymphoblastic leukemia (ALL).
Minimum Risk LevelNot Available
Health EffectsNot Available
SymptomsNot Available
TreatmentNot Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB00541
HMDB IDHMDB14681
PubChem Compound ID5978
ChEMBL IDCHEMBL90555
ChemSpider ID5758
KEGG IDC07204
UniProt IDNot Available
OMIM ID
ChEBI ID28445
BioCyc IDNot Available
CTD IDNot Available
Stitch IDNot Available
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkVincristine
References
Synthesis Reference

Homer L. Pearce, “Method of preparing vincristine.” U.S. Patent US4303584, issued November, 1967.

MSDSLink
General References
  1. Graf WD, Chance PF, Lensch MW, Eng LJ, Lipe HP, Bird TD: Severe vincristine neuropathy in Charcot-Marie-Tooth disease type 1A. Cancer. 1996 Apr 1;77(7):1356-62. [8608515 ]
  2. Qweider M, Gilsbach JM, Rohde V: Inadvertent intrathecal vincristine administration: a neurosurgical emergency. Case report. J Neurosurg Spine. 2007 Mar;6(3):280-3. [17355029 ]
  3. JOHNSON IS, ARMSTRONG JG, GORMAN M, BURNETT JP Jr: THE VINCA ALKALOIDS: A NEW CLASS OF ONCOLYTIC AGENTS. Cancer Res. 1963 Sep;23:1390-427. [14070392 ]
  4. Gidding CE, Kellie SJ, Kamps WA, de Graaf SS: Vincristine revisited. Crit Rev Oncol Hematol. 1999 Feb;29(3):267-87. [10226730 ]
  5. FDA label
  6. International Agency for Research on Cancer (2014). IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. [Link]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

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
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. [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. [17016423 ]
  3. Kurtzberg LS, Roth SD, Bagley RG, Rouleau C, Yao M, Crawford JL, Krumbholz RD, Schmid SM, Teicher BA: Bone marrow CFU-GM and human tumor xenograft efficacy of three tubulin binding agents. Cancer Chemother Pharmacol. 2009 Oct;64(5):1029-38. doi: 10.1007/s00280-009-0959-z. Epub 2009 Mar 10. [19277662 ]
  4. Gan PP, McCarroll JA, Po'uha ST, Kamath K, Jordan MA, Kavallaris M: Microtubule dynamics, mitotic arrest, and apoptosis: drug-induced differential effects of betaIII-tubulin. Mol Cancer Ther. 2010 May;9(5):1339-48. doi: 10.1158/1535-7163.MCT-09-0679. Epub 2010 May 4. [20442307 ]
General Function:
Structural constituent of cytoskeleton
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:
TUBA4A
Uniprot ID:
P68366
Molecular Weight:
49923.995 Da
References
  1. Yasui M, Koyama N, Koizumi T, Senda-Murata K, Takashima Y, Hayashi M, Sugimoto K, Honma M: Live cell imaging of micronucleus formation and development. Mutat Res. 2010 Oct 13;692(1-2):12-8. doi: 10.1016/j.mrfmmm.2010.07.009. Epub 2010 Aug 5. [20691709 ]
  2. Gan PP, McCarroll JA, Po'uha ST, Kamath K, Jordan MA, Kavallaris M: Microtubule dynamics, mitotic arrest, and apoptosis: drug-induced differential effects of betaIII-tubulin. Mol Cancer Ther. 2010 May;9(5):1339-48. doi: 10.1158/1535-7163.MCT-09-0679. Epub 2010 May 4. [20442307 ]
  3. Vilpo JA, Koski T, Vilpo LM: Selective toxicity of vincristine against chronic lymphocytic leukemia cells in vitro. Eur J Haematol. 2000 Dec;65(6):370-8. [11168494 ]
General Function:
Organic anion transmembrane transporter activity
Specific Function:
Mediates hepatobiliary excretion of numerous organic anions. May function as a cellular cisplatin transporter.
Gene Name:
ABCC2
Uniprot ID:
Q92887
Molecular Weight:
174205.64 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory802 uMNot AvailableBindingDB 50139772
References
  1. Tang F, Horie K, Borchardt RT: Are MDCK cells transfected with the human MRP2 gene a good model of the human intestinal mucosa? Pharm Res. 2002 Jun;19(6):773-9. [12134946 ]
General Function:
Xenobiotic-transporting atpase activity
Specific Function:
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name:
ABCB1
Uniprot ID:
P08183
Molecular Weight:
141477.255 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory213 uMNot AvailableBindingDB 50139772
References
  1. Tang F, Horie K, Borchardt RT: Are MDCK cells transfected with the human MDR1 gene a good model of the human intestinal mucosa? Pharm Res. 2002 Jun;19(6):765-72. [12134945 ]
General Function:
Transporter activity
Specific Function:
Mediates export of organic anions and drugs from the cytoplasm. Mediates ATP-dependent transport of glutathione and glutathione conjugates, leukotriene C4, estradiol-17-beta-o-glucuronide, methotrexate, antiviral drugs and other xenobiotics. Confers resistance to anticancer drugs. Hydrolyzes ATP with low efficiency.
Gene Name:
ABCC1
Uniprot ID:
P33527
Molecular Weight:
171589.5 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC5070 uMNot AvailableBindingDB 50139772
References
  1. Loe DW, Almquist KC, Cole SP, Deeley RG: ATP-dependent 17 beta-estradiol 17-(beta-D-glucuronide) transport by multidrug resistance protein (MRP). Inhibition by cholestatic steroids. J Biol Chem. 1996 Apr 19;271(16):9683-9. [8621644 ]
General Function:
Sodium-independent organic anion transmembrane transporter activity
Specific Function:
Mediates the Na(+)-independent uptake of organic anions such as pravastatin, taurocholate, methotrexate, dehydroepiandrosterone sulfate, 17-beta-glucuronosyl estradiol, estrone sulfate, prostaglandin E2, thromboxane B2, leukotriene C3, leukotriene E4, thyroxine and triiodothyronine. Involved in the clearance of bile acids and organic anions from the liver.
Gene Name:
SLCO1B1
Uniprot ID:
Q9Y6L6
Molecular Weight:
76447.99 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory42 uMNot AvailableBindingDB 50139772
IC5044 uMNot AvailableBindingDB 50139772
References
  1. Karlgren M, Vildhede A, Norinder U, Wisniewski JR, Kimoto E, Lai Y, Haglund U, Artursson P: Classification of inhibitors of hepatic organic anion transporting polypeptides (OATPs): influence of protein expression on drug-drug interactions. J Med Chem. 2012 May 24;55(10):4740-63. doi: 10.1021/jm300212s. Epub 2012 May 15. [22541068 ]
General Function:
Sodium-independent organic anion transmembrane transporter activity
Specific Function:
Mediates the Na(+)-independent uptake of organic anions such as 17-beta-glucuronosyl estradiol, taurocholate, triiodothyronine (T3), leukotriene C4, dehydroepiandrosterone sulfate (DHEAS), methotrexate and sulfobromophthalein (BSP). Involved in the clearance of bile acids and organic anions from the liver.
Gene Name:
SLCO1B3
Uniprot ID:
Q9NPD5
Molecular Weight:
77402.175 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory9.8 uMNot AvailableBindingDB 50139772
IC5011 uMNot AvailableBindingDB 50139772
References
  1. Karlgren M, Vildhede A, Norinder U, Wisniewski JR, Kimoto E, Lai Y, Haglund U, Artursson P: Classification of inhibitors of hepatic organic anion transporting polypeptides (OATPs): influence of protein expression on drug-drug interactions. J Med Chem. 2012 May 24;55(10):4740-63. doi: 10.1021/jm300212s. Epub 2012 May 15. [22541068 ]