Vinblastine

Identification

Summary

Vinblastine is a vinca alkaloid used to treat breast cancer, testicular cancer, neuroblastoma, Hodgkin's and non-Hodgkins lymphoma, mycosis fungoides, histiocytosis, and Kaposi's sarcoma.

Generic Name

Vinblastine

DrugBank Accession Number

DB00570

Background

Antitumor alkaloid isolated from Vinca rosea. (Merck, 11th ed.)

Type

Small Molecule

Groups

Approved

Structure

Similar Structures

Weight: Average: 810.9741
Monoisotopic: 810.420379474
Chemical Formula: C₄₆H₅₈N₄O₉

Synonyms

Vinblastin
Vinblastina
Vinblastine
Vinblastinum
Vincaleukoblastine

External IDs

NSC-47842

Poor quality drug data slowing you down?

Unlock 38% more drug discovery time and eliminate decision-making doubts with this one-stop guide to quality drug data.

Download eBook

Poor quality drug data slowing you down?

Download eBook

Pharmacology

Indication

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

Reduce drug development failure rates

Build, train, & validate machine-learning models
with evidence-based and structured datasets.

See how

Build, train, & validate predictive machine-learning models with structured datasets.

See how

Associated Conditions

Indication Type	Indication	Approval Level
Used in combination to treat	Advanced soft tissue sarcoma	••• •••••
Treatment of	Autoimmune hemolytic anemia	••• •••••
Used in combination to treat	Bladder cancer	••• •••••
Treatment of	Hodgkin lymphoma	••••••••••••
Treatment of	Immune thrombocytopenic purpura	••• •••••

Contraindications & Blackbox Warnings

Prevent Adverse Drug Events Today

Tap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.

Learn more

Avoid life-threatening adverse drug events with our Clinical API

Learn more

Pharmacodynamics

Vinblastine is a vinca alkaloid antineoplastic agent. The vinca alkaloids are structurally similar compounds comprised of 2 multiringed units: vindoline and catharanthine. The vinca alkaloids have become clinically useful since the discovery of their antitumour properties in 1959. Initially, extracts of the periwinkle plant (Catharanthus roseus) were investigated because of putative hypoglycemic properties, but were noted to cause marrow suppression in rats and antileukemic effects in vitro. Vinblastine has some immunosuppressant effect. The vinca alkaloids are considered to be cell cycle phase-specific.

Mechanism of action

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.

Target	Actions	Organism
ATubulin alpha-1A chain	binder	Humans
ATubulin beta chain	binder	Humans
ATubulin delta chain	binder	Humans
ATubulin gamma-1 chain	binder	Humans
ATubulin epsilon chain	binder	Humans
NTranscription factor AP-1	other/unknown	Humans

Absorption

Not Available

Volume of distribution

Not Available

Protein binding

98-99%

Metabolism

Hepatic. Metabolism of vinblastine has been shown to be mediated by hepatic cytochrome P450 3A isoenzymes.

Hover over products below to view reaction partners

Vinblastine
- Desacetylvinblastine

Route of elimination

The major route of excretion may be through the biliary system.

Half-life

Triphasic: 35 min, 53 min, and 19 hours

Clearance

Not Available

Adverse Effects

Improve decision support & research outcomes

With structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!

See the data

Improve decision support & research outcomes with our structured adverse effects data.

See a data sample

Toxicity

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

Pathways

Pathway	Category
Vinblastine Action Pathway	Drug action

Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">

Not Available

Interactions

Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">

This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.

Drug	Interaction
Integrate drug-drug interactions in your software
Abametapir	The serum concentration of Vinblastine can be increased when it is combined with Abametapir.
Abatacept	The metabolism of Vinblastine can be increased when combined with Abatacept.
Abciximab	The risk or severity of bleeding can be increased when Abciximab is combined with Vinblastine.
Abemaciclib	The metabolism of Abemaciclib can be increased when combined with Vinblastine.
Abrocitinib	The serum concentration of Vinblastine can be increased when it is combined with Abrocitinib.

Food Interactions

Avoid grapefruit products. Grapefruit inhibits CYP3A metabolism, which may increase the serum concentration of vinblastine.
Exercise caution with St. John's Wort. This herb induces CYP3A metabolism, which may reduce serum levels of vinblastine.

Products

Drug product information from 10+ global regions

Our datasets provide approved product information including:
dosage, form, labeller, route of administration, and marketing period.

Access now

Access drug product information from over 10 global regions.

Access now

Product Ingredients

Ingredient	UNII	CAS	InChI Key
Vinblastine sulfate	N00W22YO2B	143-67-9	KDQAABAKXDWYSZ-PNYVAJAMSA-N

International/Other Brands

Blastivin (Pharmachemie) / Cytoblastin (Cipla) / Lemblastine / Oncostin (Cipla) / Velban (ABL Antibióticos do Brasil) / Velbastin (Korea United Pharm) / Velbe (STADA) / Vinblasin (Teva) / Vinblastin (Gedeon Richter) / Vinko (Koçak) / Weibaoding (Hospira) / Xintoprost (Richmond)

Brand Name Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End
Velbe 1mg/ml	Powder, for solution	10 mg / 10 mL	Intravenous	Eli Lilly & Co. Ltd.	1994-11-15	2000-10-02
Vinblastine Sulfate Inj 1mg/ml	Liquid	1 mg / mL	Intravenous	David Bull Laboratories (Pty) Ltd.	1992-12-31	1998-08-13
Vinblastine Sulfate Injection	Solution	1 mg / mL	Intravenous	Pfizer Canada Ulc	1998-04-14	Not applicable
Vinblastine Sulfate Injection	Solution	1 mg / mL	Intravenous	Sandoz Canada Incorporated	Not applicable	Not applicable
Vinblastine Sulphate Injection	Solution	1 mg / mL	Intravenous	TEVA Canada Limited	2013-02-08	Not applicable

Generic Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End	Region	Image
Vinblastine Sulfate	Injection	1 mg/1mL	Intravenous	Fresenius Kabi USA, LLC	2000-07-12	Not applicable
Vinblastine Sulfate	Injection, powder, lyophilized, for solution	10 mg/10mL	Intravenous	Bedford Pharmaceuticals	1996-05-01	2013-04-30

Chemical Identifiers

UNII: 5V9KLZ54CY
CAS number: 865-21-4
InChI Key: JXLYSJRDGCGARV-CFWMRBGOSA-N
InChI: 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-/m0/s1
IUPAC Name: methyl (1R,9R,10S,11R,12R,19R)-11-(acetyloxy)-12-ethyl-4-[(13S,15R,17S)-17-ethyl-17-hydroxy-13-(methoxycarbonyl)-1,11-diazatetracyclo[13.3.1.0^{4,12}.0^{5,10}]nonadeca-4(12),5(10),6,8-tetraen-13-yl]-10-hydroxy-5-methoxy-8-methyl-8,16-diazapentacyclo[10.6.1.0^{1,9}.0^{2,7}.0^{16,19}]nonadeca-2,4,6,13-tetraene-10-carboxylate
SMILES: [H][C@@]12N(C)C3=CC(OC)=C(C=C3[C@@]11CCN3CC=C[C@@](CC)([C@@H](OC(C)=O)[C@]2(O)C(=O)OC)[C@@]13[H])[C@]1(C[C@@]2([H])CN(C[C@](O)(CC)C2)CCC2=C1NC1=C2C=CC=C1)C(=O)OC

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.

US4305875

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. [Article]

External Links

PubChem Compound: 13342
PubChem Substance: 46504550
ChemSpider: 12773
BindingDB: 50012278
RxNav: 11198
ChEMBL: CHEMBL159
ZINC: ZINC000085432544
Therapeutic Targets Database: DAP000785
PharmGKB: PA451877
PDBe Ligand: VLB
RxList: RxList Drug Page
Drugs.com: Drugs.com Drug Page
Wikipedia: Vinblastine

PDB Entries

1z2b / 4eb6 / 5bmv / 5j2t / 7z7d / 8cle / 8clh

MSDS

Download (73.5 KB)

Clinical Trials

Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">

Phase	Status	Purpose	Conditions	Count
4	Completed	Treatment	Lymphoma	1
4	Completed	Treatment	Non-Small Cell Lung Carcinoma	1
4	Recruiting	Treatment	Pediatric Hodgkin's Disease	1
4	Unknown Status	Treatment	Non-Hodgkin's Lymphoma (NHL)	1
3	Active Not Recruiting	Treatment	Ann Arbor Stage III Hodgkin Lymphoma / Ann Arbor Stage III Lymphocyte-Depleted Classic Hodgkin Lymphoma / Ann Arbor Stage III Mixed Cellularity Classic Hodgkin Lymphoma / Ann Arbor Stage III Nodular Sclerosis Classic Hodgkin Lymphoma / Ann Arbor Stage IV Hodgkin Lymphoma / Ann Arbor Stage IV Lymphocyte-Depleted Classic Hodgkin Lymphoma / Ann Arbor Stage IV Mixed Cellularity Classic Hodgkin Lymphoma / Ann Arbor Stage IV Nodular Sclerosis Classic Hodgkin Lymphoma / Classical Hodgkin's Lymphoma / Lymphocyte-Rich Classical Hodgkin Lymphoma	1

Pharmacoeconomics

Manufacturers

Eli lilly and co
Abraxis pharmaceutical products
App pharmaceuticals llc
Bedford laboratories div ben venue laboratories inc
Hospira inc

Packagers

APP Pharmaceuticals
APPD
Bedford Labs
Ben Venue Laboratories Inc.
Hospira Inc.

Dosage Forms

Form	Route	Strength
Solution	Intravenous	10.000 mg
Injection	Intravenous
Injection	Intravenous	1 mg/ml
Solution	Intravenous	10 mg
Solution	Intravenous	1000000 mg
Solution	Intravenous
Injection, powder, for solution	Intravenous	10 mg
Injection, solution	Intravenous	10 mg
Powder, for solution	Parenteral	10 MG
Powder, for solution	Intravenous	10 mg / 10 mL
Powder, for solution	Intravenous
Injection, powder, lyophilized, for solution	Intravenous	10 mg
Injection, solution	Parenteral	1 MG/ML
Injection, powder, lyophilized, for solution	Parenteral	10 mg
Injection, solution		5 mg
Injection	Intravenous	1 mg/1mL
Injection, powder, lyophilized, for solution	Intravenous	10 mg/10mL
Liquid	Intravenous	1 mg / mL
Solution	Intravenous	1 mg / mL
Solution	Intravenous	10 mg/1vial

Prices

Unit description	Cost	Unit
Vinblastine sulf 10 mg vial	18.6USD	each

DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.

Patents

Not Available

Properties

State

Solid

Experimental Properties

Property	Value	Source
melting point (°C)	267 °C	Not Available
water solubility	Negligible	Not Available
logP	3.70	SANGSTER (1994)

Predicted Properties

Property	Value	Source
Water Solubility	0.0169 mg/mL	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	87.46 Å³	Chemaxon
Number of Rings	9	Chemaxon
Bioavailability	1	Chemaxon
Rule of Five	No	Chemaxon
Ghose Filter	No	Chemaxon
Veber's Rule	No	Chemaxon
MDDR-like Rule	Yes	Chemaxon

Predicted ADMET Features

Property	Value	Probability
Human Intestinal Absorption	+	0.9806
Blood Brain Barrier	-	0.9203
Caco-2 permeable	+	0.6283
P-glycoprotein substrate	Substrate	0.9213
P-glycoprotein inhibitor I	Inhibitor	0.7737
P-glycoprotein inhibitor II	Inhibitor	0.6817
Renal organic cation transporter	Non-inhibitor	0.771
CYP450 2C9 substrate	Non-substrate	0.816
CYP450 2D6 substrate	Non-substrate	0.9117
CYP450 3A4 substrate	Substrate	0.72
CYP450 1A2 substrate	Non-inhibitor	0.9198
CYP450 2C9 inhibitor	Non-inhibitor	0.9093
CYP450 2D6 inhibitor	Non-inhibitor	0.9231
CYP450 2C19 inhibitor	Non-inhibitor	0.9025
CYP450 3A4 inhibitor	Non-inhibitor	0.8149
CYP450 inhibitory promiscuity	Low CYP Inhibitory Promiscuity	0.8681
Ames test	Non AMES toxic	0.9132
Carcinogenicity	Non-carcinogens	0.91
Biodegradation	Not ready biodegradable	1.0
Rat acute toxicity	2.9111 LD50, mol/kg	Not applicable
hERG inhibition (predictor I)	Weak inhibitor	0.9366
hERG inhibition (predictor II)	Non-inhibitor	0.5793

ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)

Not Available

Spectra

Spectrum	Spectrum Type	Splash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)	Predicted LC-MS/MS	splash10-03ec-0000000960-4db327c7d2cf00b7d0c6
Predicted MS/MS Spectrum - 10V, Negative (Annotated)	Predicted LC-MS/MS	splash10-0aor-4000001910-6b0d6bf84994c2aa2f33
Predicted MS/MS Spectrum - 20V, Positive (Annotated)	Predicted LC-MS/MS	splash10-01qc-0000000910-ec1cfa7cbddd9289d79c
Predicted MS/MS Spectrum - 20V, Negative (Annotated)	Predicted LC-MS/MS	splash10-0a4i-9000004310-ded40cbbe0941aa4a46f
Predicted MS/MS Spectrum - 40V, Positive (Annotated)	Predicted LC-MS/MS	splash10-0019-0112301910-13d3864d62f77c991ecb
Predicted MS/MS Spectrum - 40V, Negative (Annotated)	Predicted LC-MS/MS	splash10-052f-9010003400-435563e484e4c93ba0e6

Chromatographic Properties

Collision Cross Sections (CCS)

Adduct	CCS Value (Å²)	Source type	Source
[M-H]-	298.2963632	predicted	DarkChem Lite v0.1.0
[M-H]-	248.36577	predicted	DeepCCS 1.0 (2019)
[M+H]+	250.03435	predicted	DeepCCS 1.0 (2019)
[M+Na]+	256.81277	predicted	DeepCCS 1.0 (2019)

Targets

Build, predict & validate machine-learning models

Use our structured and evidence-based datasets to unlock new
insights and accelerate drug research.

Learn more

Use our structured and evidence-based datasets to unlock new insights and accelerate drug research.

Learn more

Details1. Tubulin alpha-1A chain

Kind: Protein
Organism: Humans
Pharmacological action: Yes
Actions: Binder

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
Uniprot Name: Tubulin alpha-1A chain
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. [Article]
Correia JJ: Effects of antimitotic agents on tubulin-nucleotide interactions. Pharmacol Ther. 1991 Nov;52(2):127-47. [Article]
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. [Article]
Islam MN, Iskander MN: Microtubulin binding sites as target for developing anticancer agents. Mini Rev Med Chem. 2004 Dec;4(10):1077-104. [Article]
Gupta S, Bhattacharyya B: Antimicrotubular drugs binding to vinca domain of tubulin. Mol Cell Biochem. 2003 Nov;253(1-2):41-7. [Article]

Details2. Tubulin beta chain

Kind: Protein
Organism: Humans
Pharmacological action: Yes
Actions: Binder

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
Uniprot Name: Tubulin beta chain
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. [Article]
Correia JJ: Effects of antimitotic agents on tubulin-nucleotide interactions. Pharmacol Ther. 1991 Nov;52(2):127-47. [Article]
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. [Article]
Islam MN, Iskander MN: Microtubulin binding sites as target for developing anticancer agents. Mini Rev Med Chem. 2004 Dec;4(10):1077-104. [Article]
Gupta S, Bhattacharyya B: Antimicrotubular drugs binding to vinca domain of tubulin. Mol Cell Biochem. 2003 Nov;253(1-2):41-7. [Article]

Details3. Tubulin delta chain

Kind: Protein
Organism: Humans
Pharmacological action: Yes
Actions: Binder

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
Uniprot Name: Tubulin delta chain
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. [Article]
Correia JJ: Effects of antimitotic agents on tubulin-nucleotide interactions. Pharmacol Ther. 1991 Nov;52(2):127-47. [Article]
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. [Article]
Islam MN, Iskander MN: Microtubulin binding sites as target for developing anticancer agents. Mini Rev Med Chem. 2004 Dec;4(10):1077-104. [Article]
Gupta S, Bhattacharyya B: Antimicrotubular drugs binding to vinca domain of tubulin. Mol Cell Biochem. 2003 Nov;253(1-2):41-7. [Article]

Details4. Tubulin gamma-1 chain

Kind: Protein
Organism: Humans
Pharmacological action: Yes
Actions: Binder

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...
Gene Name: TUBG1
Uniprot ID: P23258
Uniprot Name: Tubulin gamma-1 chain
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. [Article]
Correia JJ: Effects of antimitotic agents on tubulin-nucleotide interactions. Pharmacol Ther. 1991 Nov;52(2):127-47. [Article]
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. [Article]
Islam MN, Iskander MN: Microtubulin binding sites as target for developing anticancer agents. Mini Rev Med Chem. 2004 Dec;4(10):1077-104. [Article]
Gupta S, Bhattacharyya B: Antimicrotubular drugs binding to vinca domain of tubulin. Mol Cell Biochem. 2003 Nov;253(1-2):41-7. [Article]

Details5. Tubulin epsilon chain

Kind: Protein
Organism: Humans
Pharmacological action: Yes
Actions: Binder

General Function: Structural constituent of cytoskeleton
Specific Function: Not Available
Gene Name: TUBE1
Uniprot ID: Q9UJT0
Uniprot Name: Tubulin epsilon chain
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. [Article]
Correia JJ: Effects of antimitotic agents on tubulin-nucleotide interactions. Pharmacol Ther. 1991 Nov;52(2):127-47. [Article]
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. [Article]
Islam MN, Iskander MN: Microtubulin binding sites as target for developing anticancer agents. Mini Rev Med Chem. 2004 Dec;4(10):1077-104. [Article]
Gupta S, Bhattacharyya B: Antimicrotubular drugs binding to vinca domain of tubulin. Mol Cell Biochem. 2003 Nov;253(1-2):41-7. [Article]

Details6. Transcription factor AP-1

Kind: Protein
Organism: Humans
Pharmacological action: No
Actions: Other/unknown

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 expre...
Gene Name: JUN
Uniprot ID: P05412
Uniprot Name: Transcription factor AP-1
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. [Article]
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. [Article]
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. [Article]
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. [Article]
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. [Article]

Enzymes

Details1. Cytochrome P450 2D6

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Inhibitor

General Function: Steroid hydroxylase activity
Specific Function: Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
Gene Name: CYP2D6
Uniprot ID: P10635
Uniprot Name: Cytochrome P450 2D6
Molecular Weight: 55768.94 Da

References

Le Guellec C, Lacarelle B, Catalin J, Durand A: Inhibitory effects of anticancer drugs on dextromethorphan-O-demethylase activity in human liver microsomes. Cancer Chemother Pharmacol. 1993;32(6):491-5. [Article]

Property	Measurement	pH	Temperature (°C)	References
IC 50 (nM)	26000	N/A	N/A	A15818

Details2. Cytochrome P450 3A4

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Substrate
Inhibitor
Inducer

General Function: Vitamin d3 25-hydroxylase activity
Specific Function: 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 react...
Gene Name: CYP3A4
Uniprot ID: P08684
Uniprot Name: Cytochrome P450 3A4
Molecular Weight: 57342.67 Da

References

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. [Article]
Smith NF, Mani S, Schuetz EG, Yasuda K, Sissung TM, Bates SE, Figg WD, Sparreboom A: Induction of CYP3A4 by vinblastine: Role of the nuclear receptor NR1I2. Ann Pharmacother. 2010 Nov;44(11):1709-17. doi: 10.1345/aph.1P354. Epub 2010 Oct 19. [Article]
Baumhakel M, Kasel D, Rao-Schymanski RA, Bocker R, Beckurts KT, Zaigler M, Barthold D, Fuhr U: Screening for inhibitory effects of antineoplastic agents on CYP3A4 in human liver microsomes. Int J Clin Pharmacol Ther. 2001 Dec;39(12):517-28. [Article]

Transporters

Property	Measurement	pH	Temperature (°C)	References
EC 50 (nM)	14600	N/A	N/A	A15921
EC 50 (nM)	34000	N/A	N/A	A15921
IC 50 (nM)	29500	N/A	N/A	A15813
IC 50 (nM)	17700	N/A	N/A	A15813
IC 50 (nM)	19900	N/A	N/A	A15813
IC 50 (nM)	34000	N/A	N/A	A27451
IC 50 (nM)	2000	N/A	N/A	A15818
IC 50 (nM)	>50000	N/A	N/A	A15818
IC 50 (nM)	29000	N/A	N/A	A15931
IC 50 (nM)	10471	N/A	N/A	A27306
IC 50 (nM)	10000	N/A	N/A	A27306
IC 50 (nM)	8709636	N/A	N/A	A27306
Kd (nM)	3000	N/A	N/A	A15933
Ki (nM)	2100	N/A	N/A	A15930
Ki (nM)	140000	N/A	N/A	A15815
Ki (nM)	100	N/A	N/A	A27451
Ki (nM)	1300	N/A	N/A	A27451

Details1. P-glycoprotein 1

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Substrate
Inhibitor
Inducer

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
Uniprot Name: Multidrug resistance protein 1
Molecular Weight: 141477.255 Da

References

Arora A, Shukla Y: Modulation of vinca-alkaloid induced P-glycoprotein expression by indole-3-carbinol. Cancer Lett. 2003 Jan 28;189(2):167-73. [Article]
Gao J, Murase O, Schowen RL, Aube J, Borchardt RT: A functional assay for quantitation of the apparent affinities of ligands of P-glycoprotein in Caco-2 cells. Pharm Res. 2001 Feb;18(2):171-6. [Article]
Wang EJ, Casciano CN, Clement RP, Johnson WW: Active transport of fluorescent P-glycoprotein substrates: evaluation as markers and interaction with inhibitors. Biochem Biophys Res Commun. 2001 Nov 30;289(2):580-5. [Article]
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. [Article]
Horie K, Tang F, Borchardt RT: Isolation and characterization of Caco-2 subclones expressing high levels of multidrug resistance protein efflux transporter. Pharm Res. 2003 Feb;20(2):161-8. [Article]
Schwab D, Fischer H, Tabatabaei A, Poli S, Huwyler J: Comparison of in vitro P-glycoprotein screening assays: recommendations for their use in drug discovery. J Med Chem. 2003 Apr 24;46(9):1716-25. [Article]
Tanigawara Y, Okamura N, Hirai M, Yasuhara M, Ueda K, Kioka N, Komano T, Hori R: Transport of digoxin by human P-glycoprotein expressed in a porcine kidney epithelial cell line (LLC-PK1). J Pharmacol Exp Ther. 1992 Nov;263(2):840-5. [Article]
Tiberghien F, Loor F: Ranking of P-glycoprotein substrates and inhibitors by a calcein-AM fluorometry screening assay. Anticancer Drugs. 1996 Jul;7(5):568-78. [Article]
Pouliot JF, L'Heureux F, Liu Z, Prichard RK, Georges E: Reversal of P-glycoprotein-associated multidrug resistance by ivermectin. Biochem Pharmacol. 1997 Jan 10;53(1):17-25. [Article]
Smit JW, Weert B, Schinkel AH, Meijer DK: Heterologous expression of various P-glycoproteins in polarized epithelial cells induces directional transport of small (type 1) and bulky (type 2) cationic drugs. J Pharmacol Exp Ther. 1998 Jul;286(1):321-7. [Article]
Shepard RL, Winter MA, Hsaio SC, Pearce HL, Beck WT, Dantzig AH: Effect of modulators on the ATPase activity and vanadate nucleotide trapping of human P-glycoprotein. Biochem Pharmacol. 1998 Sep 15;56(6):719-27. [Article]
Golstein PE, Boom A, van Geffel J, Jacobs P, Masereel B, Beauwens R: P-glycoprotein inhibition by glibenclamide and related compounds. Pflugers Arch. 1999 Apr;437(5):652-60. [Article]
Takara K, Tanigawara Y, Komada F, Nishiguchi K, Sakaeda T, Okumura K: Cellular pharmacokinetic aspects of reversal effect of itraconazole on P-glycoprotein-mediated resistance of anticancer drugs. Biol Pharm Bull. 1999 Dec;22(12):1355-9. [Article]
Nagy H, Goda K, Fenyvesi F, Bacso Z, Szilasi M, Kappelmayer J, Lustyik G, Cianfriglia M, Szabo G Jr: Distinct groups of multidrug resistance modulating agents are distinguished by competition of P-glycoprotein-specific antibodies. Biochem Biophys Res Commun. 2004 Mar 19;315(4):942-9. [Article]
Chen C, Mireles RJ, Campbell SD, Lin J, Mills JB, Xu JJ, Smolarek TA: Differential interaction of 3-hydroxy-3-methylglutaryl-coa reductase inhibitors with ABCB1, ABCC2, and OATP1B1. Drug Metab Dispos. 2005 Apr;33(4):537-46. Epub 2004 Dec 22. [Article]
Yamazaki M, Neway WE, Ohe T, Chen I, Rowe JF, Hochman JH, Chiba M, Lin JH: In vitro substrate identification studies for p-glycoprotein-mediated transport: species difference and predictability of in vivo results. J Pharmacol Exp Ther. 2001 Mar;296(3):723-35. [Article]
Adachi Y, Suzuki H, Sugiyama Y: Comparative studies on in vitro methods for evaluating in vivo function of MDR1 P-glycoprotein. Pharm Res. 2001 Dec;18(12):1660-8. [Article]
Kumar S, Kwei GY, Poon GK, Iliff SA, Wang Y, Chen Q, Franklin RB, Didolkar V, Wang RW, Yamazaki M, Chiu SH, Lin JH, Pearson PG, Baillie TA: Pharmacokinetics and interactions of a novel antagonist of chemokine receptor 5 (CCR5) with ritonavir in rats and monkeys: role of CYP3A and P-glycoprotein. J Pharmacol Exp Ther. 2003 Mar;304(3):1161-71. [Article]
Atkinson DE, Greenwood SL, Sibley CP, Glazier JD, Fairbairn LJ: Role of MDR1 and MRP1 in trophoblast cells, elucidated using retroviral gene transfer. Am J Physiol Cell Physiol. 2003 Sep;285(3):C584-91. Epub 2003 Apr 30. [Article]
Troutman MD, Thakker DR: Novel experimental parameters to quantify the modulation of absorptive and secretory transport of compounds by P-glycoprotein in cell culture models of intestinal epithelium. Pharm Res. 2003 Aug;20(8):1210-24. [Article]
Dagenais C, Graff CL, Pollack GM: Variable modulation of opioid brain uptake by P-glycoprotein in mice. Biochem Pharmacol. 2004 Jan 15;67(2):269-76. [Article]
Taipalensuu J, Tavelin S, Lazorova L, Svensson AC, Artursson P: Exploring the quantitative relationship between the level of MDR1 transcript, protein and function using digoxin as a marker of MDR1-dependent drug efflux activity. Eur J Pharm Sci. 2004 Jan;21(1):69-75. [Article]
Hunter J, Hirst BH, Simmons NL: Drug absorption limited by P-glycoprotein-mediated secretory drug transport in human intestinal epithelial Caco-2 cell layers. Pharm Res. 1993 May;10(5):743-9. [Article]
Borgnia MJ, Eytan GD, Assaraf YG: Competition of hydrophobic peptides, cytotoxic drugs, and chemosensitizers on a common P-glycoprotein pharmacophore as revealed by its ATPase activity. J Biol Chem. 1996 Feb 9;271(6):3163-71. [Article]
Dantzig AH, Shepard RL, Law KL, Tabas L, Pratt S, Gillespie JS, Binkley SN, Kuhfeld MT, Starling JJ, Wrighton SA: Selectivity of the multidrug resistance modulator, LY335979, for P-glycoprotein and effect on cytochrome P-450 activities. J Pharmacol Exp Ther. 1999 Aug;290(2):854-62. [Article]
Lecureur V, Sun D, Hargrove P, Schuetz EG, Kim RB, Lan LB, Schuetz JD: Cloning and expression of murine sister of P-glycoprotein reveals a more discriminating transporter than MDR1/P-glycoprotein. Mol Pharmacol. 2000 Jan;57(1):24-35. [Article]
Fedoruk MN, Gimenez-Bonafe P, Guns ES, Mayer LD, Nelson CC: P-glycoprotein increases the efflux of the androgen dihydrotestosterone and reduces androgen responsive gene activity in prostate tumor cells. Prostate. 2004 Apr 1;59(1):77-90. [Article]
Takara K, Sakaeda T, Kakumoto M, Tanigawara Y, Kobayashi H, Okumura K, Ohnishi N, Yokoyama T: Effects of alpha-adrenoceptor antagonist doxazosin on MDR1-mediated multidrug resistance and transcellular transport. Oncol Res. 2009;17(11-12):527-33. [Article]
Jutabha P, Wempe MF, Anzai N, Otomo J, Kadota T, Endou H: Xenopus laevis oocytes expressing human P-glycoprotein: probing trans- and cis-inhibitory effects on [3H]vinblastine and [3H]digoxin efflux. Pharmacol Res. 2010 Jan;61(1):76-84. doi: 10.1016/j.phrs.2009.07.002. Epub 2009 Jul 21. [Article]
Kugawa F, Suzuki T, Miyata M, Tomono K, Tamanoi F: Construction of a model cell line for the assay of MDR1 (multi drug resistance gene-1) substrates/inhibitors using HeLa cells. Pharmazie. 2009 May;64(5):296-300. [Article]
Woodahl EL, Crouthamel MH, Bui T, Shen DD, Ho RJ: MDR1 (ABCB1) G1199A (Ser400Asn) polymorphism alters transepithelial permeability and sensitivity to anticancer agents. Cancer Chemother Pharmacol. 2009 Jun;64(1):183-8. doi: 10.1007/s00280-008-0906-4. Epub 2009 Jan 4. [Article]
Ekins S, Kim RB, Leake BF, Dantzig AH, Schuetz EG, Lan LB, Yasuda K, Shepard RL, Winter MA, Schuetz JD, Wikel JH, Wrighton SA: Application of three-dimensional quantitative structure-activity relationships of P-glycoprotein inhibitors and substrates. Mol Pharmacol. 2002 May;61(5):974-81. [Article]
Takara K, Sakaeda T, Yagami T, Kobayashi H, Ohmoto N, Horinouchi M, Nishiguchi K, Okumura K: Cytotoxic effects of 27 anticancer drugs in HeLa and MDR1-overexpressing derivative cell lines. Biol Pharm Bull. 2002 Jun;25(6):771-8. [Article]
Henning U, Loffler S, Krieger K, Klimke A: Uptake of clozapine into HL-60 promyelocytic leukaemia cells. Pharmacopsychiatry. 2002 May;35(3):90-5. [Article]

Property	Measurement	pH	Temperature (°C)	References
IC 50 (nM)	30000	N/A	N/A	A15963

Details2. Multidrug resistance-associated protein 1

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Substrate
Inhibitor
Inducer

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, methotre...
Gene Name: ABCC1
Uniprot ID: P33527
Uniprot Name: Multidrug resistance-associated protein 1
Molecular Weight: 171589.5 Da

References

Schrenk D, Baus PR, Ermel N, Klein C, Vorderstemann B, Kauffmann HM: Up-regulation of transporters of the MRP family by drugs and toxins. Toxicol Lett. 2001 Mar 31;120(1-3):51-7. [Article]
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. [Article]
Flanagan SD, Cummins CL, Susanto M, Liu X, Takahashi LH, Benet LZ: Comparison of furosemide and vinblastine secretion from cell lines overexpressing multidrug resistance protein (P-glycoprotein) and multidrug resistance-associated proteins (MRP1 and MRP2). Pharmacology. 2002;64(3):126-34. [Article]
Yildiz M, Celik-Ozenci C, Akan S, Akan I, Sati L, Demir R, Savas B, Ozben T, Samur M, Ozdogan M, Artac M, Bozcuk H: Zoledronic acid is synergic with vinblastine to induce apoptosis in a multidrug resistance protein-1 dependent way: an in vitro study. Cell Biol Int. 2006 Mar;30(3):278-82. Epub 2006 Feb 2. [Article]

Property	Measurement	pH	Temperature (°C)	References
IC 50 (nM)	21000	N/A	N/A	A15931

Details3. Canalicular multispecific organic anion transporter 1

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Substrate
Inhibitor
Inducer

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
Uniprot Name: Canalicular multispecific organic anion transporter 1
Molecular Weight: 174205.64 Da

References

Schrenk D, Baus PR, Ermel N, Klein C, Vorderstemann B, Kauffmann HM: Up-regulation of transporters of the MRP family by drugs and toxins. Toxicol Lett. 2001 Mar 31;120(1-3):51-7. [Article]
Chen C, Mireles RJ, Campbell SD, Lin J, Mills JB, Xu JJ, Smolarek TA: Differential interaction of 3-hydroxy-3-methylglutaryl-coa reductase inhibitors with ABCB1, ABCC2, and OATP1B1. Drug Metab Dispos. 2005 Apr;33(4):537-46. Epub 2004 Dec 22. [Article]
Ishikawa T, Muller M, Klunemann C, Schaub T, Keppler D: ATP-dependent primary active transport of cysteinyl leukotrienes across liver canalicular membrane. Role of the ATP-dependent transport system for glutathione S-conjugates. J Biol Chem. 1990 Nov 5;265(31):19279-86. [Article]
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. [Article]
Baltes S, Gastens AM, Fedrowitz M, Potschka H, Kaever V, Loscher W: Differences in the transport of the antiepileptic drugs phenytoin, levetiracetam and carbamazepine by human and mouse P-glycoprotein. Neuropharmacology. 2007 Feb;52(2):333-46. Epub 2006 Oct 10. [Article]

Details4. Multidrug resistance-associated protein 6

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Inhibitor

General Function: Transporter activity
Specific Function: Isoform 1: May participate directly in the active transport of drugs into subcellular organelles or influence drug distribution indirectly. Transports glutathione conjugates as leukotriene-c4 (LTC4...
Gene Name: ABCC6
Uniprot ID: O95255
Uniprot Name: Multidrug resistance-associated protein 6
Molecular Weight: 164904.81 Da

References

Cai J, Daoud R, Alqawi O, Georges E, Pelletier J, Gros P: Nucleotide binding and nucleotide hydrolysis properties of the ABC transporter MRP6 (ABCC6). Biochemistry. 2002 Jun 25;41(25):8058-67. [Article]

Property	Measurement	pH	Temperature (°C)	References
IC 50 (nM)	114700	N/A	N/A	A16121
IC 50 (nM)	62000	N/A	N/A	A16121

Details5. Bile salt export pump

Kind: Protein
Organism: Humans
Pharmacological action: No
Actions: Substrate
Inhibitor

General Function: Transporter activity
Specific Function: Involved in the ATP-dependent secretion of bile salts into the canaliculus of hepatocytes.
Gene Name: ABCB11
Uniprot ID: O95342
Uniprot Name: Bile salt export pump
Molecular Weight: 146405.83 Da

References

Wang EJ, Casciano CN, Clement RP, Johnson WW: Fluorescent substrates of sister-P-glycoprotein (BSEP) evaluated as markers of active transport and inhibition: evidence for contingent unequal binding sites. Pharm Res. 2003 Apr;20(4):537-44. [Article]
Lecureur V, Sun D, Hargrove P, Schuetz EG, Kim RB, Lan LB, Schuetz JD: Cloning and expression of murine sister of P-glycoprotein reveals a more discriminating transporter than MDR1/P-glycoprotein. Mol Pharmacol. 2000 Jan;57(1):24-35. [Article]

Details6. Solute carrier organic anion transporter family member 1B1

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Inhibitor

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, prostagland...
Gene Name: SLCO1B1
Uniprot ID: Q9Y6L6
Uniprot Name: Solute carrier organic anion transporter family member 1B1
Molecular Weight: 76447.99 Da

References

Karlgren M, Ahlin G, Bergstrom CA, Svensson R, Palm J, Artursson P: In vitro and in silico strategies to identify OATP1B1 inhibitors and predict clinical drug-drug interactions. Pharm Res. 2012 Feb;29(2):411-26. doi: 10.1007/s11095-011-0564-9. Epub 2011 Aug 23. [Article]

Drug created at June 13, 2005 13:24 / Updated at February 20, 2024 23:54

Vinblastine

Identification

Structure for Vinblastine (DB00570)

Pharmacology

Interactions

Products

Categories

Chemical Identifiers

References

Clinical Trials

Pharmacoeconomics

Properties

Spectra

Collision Cross Sections (CCS)

Targets

References

References

References

References

References

References

Enzymes

References

References

Transporters

References

References

References

References

References

References