Tmic
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Record Information
Version2.0
Creation Date2014-08-29 04:49:15 UTC
Update Date2014-12-24 20:26:35 UTC
Accession NumberT3D4017
Identification
Common NameVinblastine
ClassSmall Molecule
DescriptionVinblastine 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 vinblastine is thought to be due primarily to inhibition of mitosis at metaphase through its interaction with tubulin. Vinblastine binds to the microtubular proteins of the mitotic spindle, leading to crystallization of the microtubule and mitotic arrest or cell death.
Compound Type
  • Amine
  • Antineoplastic Agent, Phytogenic
  • Drug
  • Ester
  • Ether
  • Metabolite
  • Organic Compound
  • Synthetic Compound
  • Tubulin Modulator
Chemical Structure
Thumb
Synonyms
Synonym
(2alpha,2'BETA,3beta,4alpha,5beta)-vincaleukoblastine
Blastivin
Cytoblastin
Lemblastine
Oncostin
Velban
Velbastin
Velbe
Vinblasin
Vinblastin
Vinblastina
Vinblastinum
Vincaleukoblastine
Vinko
VLB
Weibaoding
Xintoprost
Chemical FormulaC46H58N4O9
Average Molecular Mass810.974 g/mol
Monoisotopic Mass810.420 g/mol
CAS Registry Number865-21-4
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]-10-hydroxy-5-methoxy-8-methyl-8,16-diazapentacyclo[10.6.1.0¹,⁹.0²,⁷.0¹⁶,¹⁹]nonadeca-2(7),3,5,13-tetraene-10-carboxylate
Traditional Namevinblastine
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(C[C@](O)(CC)C2)CCC2=C1NC1=CC=CC=C21)C(=O)OC
InChI IdentifierInChI=1S/C46H58N4O9/c1-8-42(54)23-28-24-45(40(52)57-6,36-30(15-19-49(25-28)26-42)29-13-10-11-14-33(29)47-36)32-21-31-34(22-35(32)56-5)48(4)38-44(31)17-20-50-18-12-16-43(9-2,37(44)50)39(59-27(3)51)46(38,55)41(53)58-7/h10-14,16,21-22,28,37-39,47,54-55H,8-9,15,17-20,23-26H2,1-7H3/t28-,37+,38-,39-,42+,43-,44-,45+,46+/m1/s1
InChI KeyInChIKey=JXLYSJRDGCGARV-XQKSVPLYSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as glutamic acid and derivatives. Glutamic acid and derivatives are compounds containing glutamic acid or a derivative thereof resulting from reaction of glutamic acid at the amino group or the carboxy group, or from the replacement of any hydrogen of glycine by a heteroatom.
KingdomOrganic compounds
Super ClassOrganic acids and derivatives
ClassCarboxylic acids and derivatives
Sub ClassAmino acids, peptides, and analogues
Direct ParentGlutamic acid and derivatives
Alternative Parents
Substituents
  • Glutamic acid or derivatives
  • Hippuric acid or derivatives
  • Hippuric acid
  • N-acyl-alpha-amino acid
  • N-acyl-alpha amino acid or derivatives
  • Aminobenzamide
  • Aminobenzoic acid or derivatives
  • Pteridine
  • Benzamide
  • Benzoic acid or derivatives
  • Benzoyl
  • Aniline or substituted anilines
  • Tertiary aliphatic/aromatic amine
  • Dialkylarylamine
  • Aminopyrimidine
  • Aralkylamine
  • Benzenoid
  • Pyrimidine
  • Pyrazine
  • Monocyclic benzene moiety
  • Dicarboxylic acid or derivatives
  • Heteroaromatic compound
  • Tertiary amine
  • Secondary carboxylic acid amide
  • Carboxamide group
  • Amino acid
  • Carboxylic acid
  • Organoheterocyclic compound
  • Azacycle
  • Organic oxygen compound
  • Primary amine
  • Carbonyl group
  • Amine
  • Organic oxide
  • Organic nitrogen compound
  • Organopnictogen compound
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen 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
PathwaysNot Available
ApplicationsNot Available
Biological RolesNot Available
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point267°C
Boiling PointNot Available
SolubilityNegligible
LogP3.7
Predicted Properties
PropertyValueSource
Water Solubility0.017 g/LALOGPS
logP4.22ALOGPS
logP4.18ChemAxon
logS-4.7ALOGPS
pKa (Strongest Acidic)10.87ChemAxon
pKa (Strongest Basic)8.86ChemAxon
Physiological Charge2ChemAxon
Hydrogen Acceptor Count9ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area154.1 ŲChemAxon
Rotatable Bond Count10ChemAxon
Refractivity222.42 m³·mol⁻¹ChemAxon
Polarizability87.3 ųChemAxon
Number of Rings9ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0ikc-0000000910-d1cb68f2685afb162accView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0uec-0000000900-d971ad5e494178026027View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0006-2200003900-b38c610455defefb74eaView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0a4i-2004000940-18f9743c5af790ad89f0View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-052r-0009000200-0c81f1924aad5a0d0289View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0a4i-9015000800-316693e83321d70e4472View in MoNA
Toxicity Profile
Route of ExposureNot Available
Mechanism of ToxicityThe antitumor activity of vinblastine is thought to be due primarily to inhibition of mitosis at metaphase through its interaction with tubulin. Vinblastine binds to the microtubular proteins of the mitotic spindle, leading to crystallization of the microtubule and mitotic arrest or cell death.
MetabolismHepatic. Metabolism of vinblastine has been shown to be mediated by hepatic cytochrome P450 3A isoenzymes. Route of Elimination: The major route of excretion may be through the biliary system. Half Life: Triphasic: 35 min, 53 min, and 19 hours
Toxicity ValuesOral, mouse: LD50 = 423 mg/kg; Oral, rat: LD50 = 305 mg/kg.
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesFor treatment of breast cancer, testicular cancer, lymphomas, neuroblastoma, Hodgkin's and non-Hodgkin's lymphomas, mycosis fungoides, histiocytosis, and Kaposi's sarcoma.
Minimum Risk LevelNot Available
Health EffectsNot Available
SymptomsNot Available
TreatmentNot Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB00570
HMDB IDHMDB14710
PubChem Compound ID241903
ChEMBL IDCHEMBL159
ChemSpider ID12773
KEGG IDC07201
UniProt IDNot Available
OMIM ID
ChEBI ID27375
BioCyc IDNot Available
CTD IDNot Available
Stitch IDNot Available
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkVinblastine
References
Synthesis Reference

Pierre Potier, Pierre Mangeney, Nicole Langlois, Yves Langlois, “Process for the synthesis of vinblastine and leurosidine.” U.S. Patent US4305875, issued October, 1977.

MSDSLink
General References
  1. Starling D: Two ultrastructurally distinct tubulin paracrystals induced in sea-urchin eggs by vinblastine sulphate. J Cell Sci. 1976 Jan;20(1):79-89. [942954 ]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

General Function:
Transcriptional activator activity, rna polymerase ii transcription factor binding
Specific Function:
Transcription factor that recognizes and binds to the enhancer heptamer motif 5'-TGA[CG]TCA-3'. Promotes activity of NR5A1 when phosphorylated by HIPK3 leading to increased steroidogenic gene expression upon cAMP signaling pathway stimulation.
Gene Name:
JUN
Uniprot ID:
P05412
Molecular Weight:
35675.32 Da
References
  1. Brantley-Finley C, Lyle CS, Du L, Goodwin ME, Hall T, Szwedo D, Kaushal GP, Chambers TC: The JNK, ERK and p53 pathways play distinct roles in apoptosis mediated by the antitumor agents vinblastine, doxorubicin, and etoposide. Biochem Pharmacol. 2003 Aug 1;66(3):459-69. [12907245 ]
  2. Bene A, Kurten RC, Chambers TC: Subcellular localization as a limiting factor for utilization of decoy oligonucleotides. Nucleic Acids Res. 2004 Oct 21;32(19):e142. [15498923 ]
  3. Obey TB, Lyle CS, Chambers TC: Role of c-Jun in cellular sensitivity to the microtubule inhibitor vinblastine. Biochem Biophys Res Commun. 2005 Oct 7;335(4):1179-84. [16111654 ]
  4. Martinez-Campa C, Casado P, Rodriguez R, Zuazua P, Garcia-Pedrero JM, Lazo PS, Ramos S: Effect of vinca alkaloids on ERalpha levels and estradiol-induced responses in MCF-7 cells. Breast Cancer Res Treat. 2006 Jul;98(1):81-9. Epub 2006 Mar 23. [16555127 ]
  5. Duan L, Sterba K, Kolomeichuk S, Kim H, Brown PH, Chambers TC: Inducible overexpression of c-Jun in MCF7 cells causes resistance to vinblastine via inhibition of drug-induced apoptosis and senescence at a step subsequent to mitotic arrest. Biochem Pharmacol. 2007 Feb 15;73(4):481-90. Epub 2006 Oct 29. [17126817 ]
General 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.
Specific Function:
Gtp binding
Gene Name:
TUBA1A
Uniprot ID:
Q71U36
Molecular Weight:
50135.25 Da
References
  1. Jordan MA, Kamath K: How do microtubule-targeted drugs work? An overview. Curr Cancer Drug Targets. 2007 Dec;7(8):730-42. [18220533 ]
  2. Correia JJ: Effects of antimitotic agents on tubulin-nucleotide interactions. Pharmacol Ther. 1991 Nov;52(2):127-47. [1818332 ]
  3. Jordan A, Hadfield JA, Lawrence NJ, McGown AT: Tubulin as a target for anticancer drugs: agents which interact with the mitotic spindle. Med Res Rev. 1998 Jul;18(4):259-96. [9664292 ]
  4. Islam MN, Iskander MN: Microtubulin binding sites as target for developing anticancer agents. Mini Rev Med Chem. 2004 Dec;4(10):1077-104. [15579115 ]
  5. Gupta S, Bhattacharyya B: Antimicrotubular drugs binding to vinca domain of tubulin. Mol Cell Biochem. 2003 Nov;253(1-2):41-7. [14619954 ]
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. Jordan MA, Kamath K: How do microtubule-targeted drugs work? An overview. Curr Cancer Drug Targets. 2007 Dec;7(8):730-42. [18220533 ]
  2. Correia JJ: Effects of antimitotic agents on tubulin-nucleotide interactions. Pharmacol Ther. 1991 Nov;52(2):127-47. [1818332 ]
  3. Jordan A, Hadfield JA, Lawrence NJ, McGown AT: Tubulin as a target for anticancer drugs: agents which interact with the mitotic spindle. Med Res Rev. 1998 Jul;18(4):259-96. [9664292 ]
  4. Islam MN, Iskander MN: Microtubulin binding sites as target for developing anticancer agents. Mini Rev Med Chem. 2004 Dec;4(10):1077-104. [15579115 ]
  5. Gupta S, Bhattacharyya B: Antimicrotubular drugs binding to vinca domain of tubulin. Mol Cell Biochem. 2003 Nov;253(1-2):41-7. [14619954 ]
General Function:
Structural constituent of cytoskeleton
Specific Function:
In the elongating spermatid it is associated with the manchette, a specialized microtubule system present during reshaping of the sperm head.
Gene Name:
TUBD1
Uniprot ID:
Q9UJT1
Molecular Weight:
51033.86 Da
References
  1. Jordan MA, Kamath K: How do microtubule-targeted drugs work? An overview. Curr Cancer Drug Targets. 2007 Dec;7(8):730-42. [18220533 ]
  2. Correia JJ: Effects of antimitotic agents on tubulin-nucleotide interactions. Pharmacol Ther. 1991 Nov;52(2):127-47. [1818332 ]
  3. Jordan A, Hadfield JA, Lawrence NJ, McGown AT: Tubulin as a target for anticancer drugs: agents which interact with the mitotic spindle. Med Res Rev. 1998 Jul;18(4):259-96. [9664292 ]
  4. Islam MN, Iskander MN: Microtubulin binding sites as target for developing anticancer agents. Mini Rev Med Chem. 2004 Dec;4(10):1077-104. [15579115 ]
  5. Gupta S, Bhattacharyya B: Antimicrotubular drugs binding to vinca domain of tubulin. Mol Cell Biochem. 2003 Nov;253(1-2):41-7. [14619954 ]
General Function:
Structural constituent of cytoskeleton
Specific Function:
Not Available
Gene Name:
TUBE1
Uniprot ID:
Q9UJT0
Molecular Weight:
52931.4 Da
References
  1. Jordan MA, Kamath K: How do microtubule-targeted drugs work? An overview. Curr Cancer Drug Targets. 2007 Dec;7(8):730-42. [18220533 ]
  2. Correia JJ: Effects of antimitotic agents on tubulin-nucleotide interactions. Pharmacol Ther. 1991 Nov;52(2):127-47. [1818332 ]
  3. Jordan A, Hadfield JA, Lawrence NJ, McGown AT: Tubulin as a target for anticancer drugs: agents which interact with the mitotic spindle. Med Res Rev. 1998 Jul;18(4):259-96. [9664292 ]
  4. Islam MN, Iskander MN: Microtubulin binding sites as target for developing anticancer agents. Mini Rev Med Chem. 2004 Dec;4(10):1077-104. [15579115 ]
  5. Gupta S, Bhattacharyya B: Antimicrotubular drugs binding to vinca domain of tubulin. Mol Cell Biochem. 2003 Nov;253(1-2):41-7. [14619954 ]
General Function:
Structural constituent of cytoskeleton
Specific Function:
Tubulin is the major constituent of microtubules. The gamma chain is found at microtubule organizing centers (MTOC) such as the spindle poles or the centrosome. Pericentriolar matrix component that regulates alpha/beta chain minus-end nucleation, centrosome duplication and spindle formation.
Gene Name:
TUBG1
Uniprot ID:
P23258
Molecular Weight:
51169.48 Da
References
  1. Jordan MA, Kamath K: How do microtubule-targeted drugs work? An overview. Curr Cancer Drug Targets. 2007 Dec;7(8):730-42. [18220533 ]
  2. Correia JJ: Effects of antimitotic agents on tubulin-nucleotide interactions. Pharmacol Ther. 1991 Nov;52(2):127-47. [1818332 ]
  3. Jordan A, Hadfield JA, Lawrence NJ, McGown AT: Tubulin as a target for anticancer drugs: agents which interact with the mitotic spindle. Med Res Rev. 1998 Jul;18(4):259-96. [9664292 ]
  4. Islam MN, Iskander MN: Microtubulin binding sites as target for developing anticancer agents. Mini Rev Med Chem. 2004 Dec;4(10):1077-104. [15579115 ]
  5. Gupta S, Bhattacharyya B: Antimicrotubular drugs binding to vinca domain of tubulin. Mol Cell Biochem. 2003 Nov;253(1-2):41-7. [14619954 ]