T3DB: Vinblastine

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Identification Taxonomy Biological Properties Physical Properties Toxicity Profile Spectra Concentrations Links References Gene Regulation Targets (6)XML

Targets (6)

Record Information

Version

2.0

Creation Date

2014-08-29 04:49:15 UTC

Update Date

2014-12-24 20:26:35 UTC

Accession Number

T3D4017

Identification

Common Name

Vinblastine

Class

Small Molecule

Description

Vinblastine 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

MOL SDF PDB SMILES InChI

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 Formula

C₄₆H₅₈N₄O₉

Average Molecular Mass

810.974 g/mol

Monoisotopic Mass

810.420 g/mol

CAS Registry Number

865-21-4

IUPAC Name

methyl (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 Name

vinblastine

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 Identifier

InChI=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 Key

InChIKey=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.

Kingdom

Organic compounds

Super Class

Organic acids and derivatives

Class

Carboxylic acids and derivatives

Sub Class

Amino acids, peptides, and analogues

Direct Parent

Glutamic 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 Framework

Aromatic heteropolycyclic compounds

External Descriptors

monocarboxylic acid amide (CHEBI:44185 )
dicarboxylic acid (CHEBI:44185 )
pteridines (CHEBI:44185 )

Biological Properties

Status

Detected and Not Quantified

Origin

Exogenous

Cellular Locations

Cytoplasm
Membrane

Biofluid Locations

Not Available

Tissue Locations

Not Available

Pathways

Not Available

Applications

Not Available

Biological Roles

Not Available

Chemical Roles

Not Available

Physical Properties

State

Solid

Appearance

White powder.

Experimental Properties

Property	Value
Melting Point	267°C
Boiling Point	Not Available
Solubility	Negligible
LogP	3.7

Predicted Properties

Property	Value	Source
Water Solubility	0.017 g/L	ALOGPS
logP	4.22	ALOGPS
logP	4.18	ChemAxon
logS	-4.7	ALOGPS
pKa (Strongest Acidic)	10.87	ChemAxon
pKa (Strongest Basic)	8.86	ChemAxon
Physiological Charge	2	ChemAxon
Hydrogen Acceptor Count	9	ChemAxon
Hydrogen Donor Count	3	ChemAxon
Polar Surface Area	154.1 Å²	ChemAxon
Rotatable Bond Count	10	ChemAxon
Refractivity	222.42 m³·mol⁻¹	ChemAxon
Polarizability	87.3 Å³	ChemAxon
Number of Rings	9	ChemAxon
Bioavailability	1	ChemAxon
Rule of Five	Yes	ChemAxon
Ghose Filter	Yes	ChemAxon
Veber's Rule	Yes	ChemAxon
MDDR-like Rule	Yes	ChemAxon

Spectra

Spectrum Type	Description	Splash Key	Deposition Date	View
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_1_1) - 70eV, Positive	Not Available	2021-10-19	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_1_2) - 70eV, Positive	Not Available	2021-10-19	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_1_3) - 70eV, Positive	Not Available	2021-10-19	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-0ikc-0000000910-d1cb68f2685afb162acc	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-0uec-0000000900-d971ad5e494178026027	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-0006-2200003900-b38c610455defefb74ea	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-0a4i-2004000940-18f9743c5af790ad89f0	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	splash10-052r-0009000200-0c81f1924aad5a0d0289	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	splash10-0a4i-9015000800-316693e83321d70e4472	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-03di-0000000290-e83796c88a86832b93fb	2021-09-22	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-03di-0000001960-9a6b45d6c00705963b0d	2021-09-22	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-02vs-0011303910-751b3b42b5bf5dec036b	2021-09-22	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-0a4i-4000004920-d63f7ed72412a0867d89	2021-09-22	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	splash10-052f-8000009500-626405ba7c9cc4bdc9dc	2021-09-22	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	splash10-0536-7050004900-0bad8ab21f2b471eb30f	2021-09-22	View Spectrum

Toxicity Profile

Route of Exposure

Not Available

Mechanism of Toxicity

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.

Metabolism

Hepatic. 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 Values

Oral, mouse: LD₅₀ = 423 mg/kg; Oral, rat: LD₅₀ = 305 mg/kg.

Lethal Dose

Not Available

Carcinogenicity (IARC Classification)

No indication of carcinogenicity to humans (not listed by IARC).

Uses/Sources

For treatment of breast cancer, testicular cancer, lymphomas, neuroblastoma, Hodgkin's and non-Hodgkin's lymphomas, mycosis fungoides, histiocytosis, and Kaposi's sarcoma.

Minimum Risk Level

Not Available

Health Effects

Not Available

Symptoms

Not Available

Treatment

Not Available

Normal Concentrations

Not Available

Abnormal Concentrations

Not Available

External Links

DrugBank ID

HMDB ID

PubChem Compound ID

ChEMBL ID

ChemSpider ID

KEGG ID

UniProt ID

Not Available

OMIM ID

ChEBI ID

27375

BioCyc ID

Not Available

CTD ID

Not Available

Stitch ID

Not Available

PDB ID

Not Available

ACToR ID

Not Available

Wikipedia Link

Vinblastine

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.

MSDS

Link

General References

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 Genes

Not Available

Down-Regulated Genes

Not Available

Targets

Target Details

1. Transcription factor AP-1

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

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 ]
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 ]
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 ]
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 ]
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 ]

Target Details

2. Tubulin alpha-1A chain

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

Jordan MA, Kamath K: How do microtubule-targeted drugs work? An overview. Curr Cancer Drug Targets. 2007 Dec;7(8):730-42. [18220533 ]
Correia JJ: Effects of antimitotic agents on tubulin-nucleotide interactions. Pharmacol Ther. 1991 Nov;52(2):127-47. [1818332 ]
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 ]
Islam MN, Iskander MN: Microtubulin binding sites as target for developing anticancer agents. Mini Rev Med Chem. 2004 Dec;4(10):1077-104. [15579115 ]
Gupta S, Bhattacharyya B: Antimicrotubular drugs binding to vinca domain of tubulin. Mol Cell Biochem. 2003 Nov;253(1-2):41-7. [14619954 ]

Target Details

3. Tubulin beta chain

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

Jordan MA, Kamath K: How do microtubule-targeted drugs work? An overview. Curr Cancer Drug Targets. 2007 Dec;7(8):730-42. [18220533 ]
Correia JJ: Effects of antimitotic agents on tubulin-nucleotide interactions. Pharmacol Ther. 1991 Nov;52(2):127-47. [1818332 ]
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 ]
Islam MN, Iskander MN: Microtubulin binding sites as target for developing anticancer agents. Mini Rev Med Chem. 2004 Dec;4(10):1077-104. [15579115 ]
Gupta S, Bhattacharyya B: Antimicrotubular drugs binding to vinca domain of tubulin. Mol Cell Biochem. 2003 Nov;253(1-2):41-7. [14619954 ]

Target Details

4. Tubulin delta chain

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

Jordan MA, Kamath K: How do microtubule-targeted drugs work? An overview. Curr Cancer Drug Targets. 2007 Dec;7(8):730-42. [18220533 ]
Correia JJ: Effects of antimitotic agents on tubulin-nucleotide interactions. Pharmacol Ther. 1991 Nov;52(2):127-47. [1818332 ]
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 ]
Islam MN, Iskander MN: Microtubulin binding sites as target for developing anticancer agents. Mini Rev Med Chem. 2004 Dec;4(10):1077-104. [15579115 ]
Gupta S, Bhattacharyya B: Antimicrotubular drugs binding to vinca domain of tubulin. Mol Cell Biochem. 2003 Nov;253(1-2):41-7. [14619954 ]

Target Details

5. Tubulin epsilon chain

General Function:: Structural constituent of cytoskeleton
Specific Function:: Not Available
Gene Name:: TUBE1
Uniprot ID:: Q9UJT0
Molecular Weight:: 52931.4 Da

References

Jordan MA, Kamath K: How do microtubule-targeted drugs work? An overview. Curr Cancer Drug Targets. 2007 Dec;7(8):730-42. [18220533 ]
Correia JJ: Effects of antimitotic agents on tubulin-nucleotide interactions. Pharmacol Ther. 1991 Nov;52(2):127-47. [1818332 ]
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 ]
Islam MN, Iskander MN: Microtubulin binding sites as target for developing anticancer agents. Mini Rev Med Chem. 2004 Dec;4(10):1077-104. [15579115 ]
Gupta S, Bhattacharyya B: Antimicrotubular drugs binding to vinca domain of tubulin. Mol Cell Biochem. 2003 Nov;253(1-2):41-7. [14619954 ]

Target Details

6. Tubulin gamma-1 chain

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

Jordan MA, Kamath K: How do microtubule-targeted drugs work? An overview. Curr Cancer Drug Targets. 2007 Dec;7(8):730-42. [18220533 ]
Correia JJ: Effects of antimitotic agents on tubulin-nucleotide interactions. Pharmacol Ther. 1991 Nov;52(2):127-47. [1818332 ]
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 ]
Islam MN, Iskander MN: Microtubulin binding sites as target for developing anticancer agents. Mini Rev Med Chem. 2004 Dec;4(10):1077-104. [15579115 ]
Gupta S, Bhattacharyya B: Antimicrotubular drugs binding to vinca domain of tubulin. Mol Cell Biochem. 2003 Nov;253(1-2):41-7. [14619954 ]

Vinblastine (T3D4017)

Structure for T3D4017: Vinblastine

Targets

References

References

References

References

References

References