Identification

Name
Vinblastine
Accession Number
DB00570  (APRD00708)
Type
Small Molecule
Groups
Approved
Description

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

Structure
Thumb
Synonyms
  • Vinblastin
  • Vinblastina
  • Vinblastine
  • Vinblastinum
  • Vincaleukoblastine
External IDs
NSC-47842
Product Ingredients
IngredientUNIICASInChI Key
Vinblastine sulfateN00W22YO2B143-67-9KDQAABAKXDWYSZ-PNYVAJAMSA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Velbe 1mg/mlPowder, for solution10 mgIntravenousEli Lilly & Co. Ltd.1994-11-152000-10-02Canada
Vinblastine Sulfate Inj 1mg/mlLiquid1 mgIntravenousDavid Bull Laboratories (Pty) Ltd.1992-12-311998-08-13Canada
Vinblastine Sulfate InjectionSolution1 mgIntravenousPfizer1998-04-14Not applicableCanada
Vinblastine Sulfate InjectionSolution1 mgIntravenousSandoz Canada IncorporatedNot applicableNot applicableCanada
Vinblastine Sulphate InjectionSolution1 mgIntravenousTeva2013-02-08Not applicableCanada
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Vinblastine SulfateInjection, powder, lyophilized, for solution10 mg/10mLIntravenousBedford Pharmaceuticals1996-05-012013-04-30Us
Vinblastine SulfateInjection1 mg/1mLIntravenousFresenius Kabi2000-07-12Not applicableUs
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)
Categories
UNII
5V9KLZ54CY
CAS number
865-21-4
Weight
Average: 810.9741
Monoisotopic: 810.420379474
Chemical Formula
C46H58N4O9
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[13.3.1.0⁴,¹².0⁵,¹⁰]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-2,4,6,13-tetraene-10-carboxylate
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

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.

Associated Conditions
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.

TargetActionsOrganism
ATubulin alpha-1A chain
adduct
Human
ATubulin beta chain
adduct
Human
ATubulin delta chain
adduct
Human
ATubulin gamma-1 chain
adduct
Human
ATubulin epsilon chain
adduct
Human
NTranscription factor AP-1
other/unknown
Human
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.

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
Toxicity

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

Affected organisms
  • Humans and other mammals
Pathways
PathwayCategory
Vinblastine Action PathwayDrug action
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe metabolism of (R)-warfarin can be increased when combined with Vinblastine.
(S)-WarfarinThe metabolism of (S)-Warfarin can be increased when combined with Vinblastine.
2-MethoxyethanolThe risk or severity of adverse effects can be increased when Vinblastine is combined with 2-Methoxyethanol.
3,5-diiodothyropropionic acidThe metabolism of 3,5-diiodothyropropionic acid can be increased when combined with Vinblastine.
4-hydroxycoumarinThe metabolism of 4-hydroxycoumarin can be increased when combined with Vinblastine.
4-MethoxyamphetamineThe metabolism of 4-Methoxyamphetamine can be decreased when combined with Vinblastine.
5-androstenedioneThe metabolism of 5-androstenedione can be increased when combined with Vinblastine.
6-Deoxyerythronolide BThe serum concentration of Vinblastine can be increased when it is combined with 6-Deoxyerythronolide B.
6-O-benzylguanineThe metabolism of 6-O-benzylguanine can be increased when combined with Vinblastine.
7-ethyl-10-hydroxycamptothecinThe metabolism of 7-ethyl-10-hydroxycamptothecin can be increased when combined with Vinblastine.
Food Interactions
Not Available

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
  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. [PubMed:942954]
External Links
PubChem Compound
13342
PubChem Substance
46504550
ChemSpider
12773
BindingDB
50012278
ChEMBL
CHEMBL159
Therapeutic Targets Database
DAP000785
PharmGKB
PA451877
HET
VLB
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Vinblastine
ATC Codes
L01CA01 — Vinblastine
AHFS Codes
  • 10:00.00 — Antineoplastic Agents
PDB Entries
1z2b / 4eb6 / 5bmv / 5j2t
MSDS
Download (73.5 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1Active Not RecruitingTreatmentCentral Nervous System / Recurrent Lymphoma / Refractory Lymphomas / Tumors, Solid1
1CompletedTreatmentBrain and Central Nervous System Tumors / Neurofibromatosis Type 11
1CompletedTreatmentHodgkins Disease (HD)1
1CompletedTreatmentLymphoma, Hodgkins1
1CompletedTreatmentNeoplasms Metastasis / Neoplasms, Kidney1
1CompletedTreatmentStage IV Melanoma1
1CompletedTreatmentTumors, Central Nervous System / Tumors, Solid1
1RecruitingTreatmentRecurrent Low-grade Gliomas / Refractory Low-grade Gliomas1
1Unknown StatusTreatmentLung Cancers2
1, 2CompletedTreatmentHodgkins Disease (HD)1
1, 2CompletedTreatmentMetastatic Melanoma1
1, 2CompletedTreatmentRecurrent Melanoma / Stage IV Skin Melanoma1
1, 2Not Yet RecruitingTreatmentChildhood Lymphoma / Childhood Solid Tumors1
1, 2RecruitingTreatmentAIDS-Related Hodgkin Lymphoma / Ann Arbor Stage II Hodgkin Lymphoma / Ann Arbor Stage IIA Hodgkin Lymphoma / Ann Arbor Stage IIB Hodgkin Lymphoma / Ann Arbor Stage III Hodgkin Lymphoma / Ann Arbor Stage IIIA Hodgkin Lymphoma / Ann Arbor Stage IIIB Hodgkin Lymphoma / Ann Arbor Stage IV Hodgkin Lymphoma / Ann Arbor Stage IVA Hodgkin Lymphoma / Ann Arbor Stage IVB Hodgkin Lymphoma / CD30-Positive Neoplastic Cells Present / Classic Hodgkin Lymphoma / Classical Hodgkin Lymphoma / Human Immunodeficiency Virus (HIV) Infections / Stage II Hodgkin Lymphoma / Stage IIA Hodgkin Lymphoma / Stage IIB Hodgkin Lymphoma / Stage III Hodgkin Lymphoma / Stage IIIA Hodgkin Lymphoma / Stage IIIB Hodgkin Lymphoma / Stage IV Hodgkin Lymphoma / Stage IVA Hodgkin Lymphoma / Stage IVB Hodgkin Lymphoma1
1, 2RecruitingTreatmentHodgkins Disease (HD)1
1, 2RecruitingTreatmentLymphoma, Hodgkins1
2Active Not RecruitingTreatmentAdult Lymphocyte Depletion Hodgkin Lymphoma / Adult Lymphocyte Predominant Hodgkin Lymphoma / Adult Mixed Cellularity Hodgkin Lymphoma / Adult Nodular Sclerosis Hodgkin Lymphoma / Stage II Adult Hodgkin Lymphoma / Stage III Adult Hodgkin Lymphoma / Stage IV Adult Hodgkin Lymphoma1
2Active Not RecruitingTreatmentClassical Hodgkin Lymphoma1
2Active Not RecruitingTreatmentGliomas1
2Active Not RecruitingTreatmentHIV-associated Hodgkin Lymphoma / Human Immunodeficiency Virus (HIV) Infections / Stage III Adult Hodgkin Lymphoma / Stage IV Adult Hodgkin Lymphoma1
2Active Not RecruitingTreatmentHodgkins Disease (HD)1
2Active Not RecruitingTreatmentLocalized Urothelial Carcinoma of the Renal Pelvis and Ureter / Recurrent Urothelial Carcinoma of the Renal Pelvis and Ureter / Regional Urothelial Carcinoma of the Renal Pelvis and Ureter1
2Active Not RecruitingTreatmentLymphoma, Hodgkins3
2Active Not RecruitingTreatmentMalignant Lymphomas / Nonneoplastic Condition1
2CompletedTreatmentAcute Lymphoblastic Leukaemias (ALL) / Lymphoma, Lymphoblastic1
2CompletedTreatmentBladder Cancers2
2CompletedTreatmentBladder Cancers / Muscle-invasive Bladder Cancer1
2CompletedTreatmentClassic Hodgkin Lymphoma / Lugano Classification Stage III Hodgkin Lymphoma AJCC v8 / Lugano Classification Stage IV Hodgkin Lymphoma AJCC v8 / Lymphoma, Hodgkins1
2CompletedTreatmentDesmoid Tumors1
2CompletedTreatmentGliomas1
2CompletedTreatmentHigh Risk Urothelial Carcinoma of the Upper Urinary Tracts / Muscle Invasive Bladder Cancer1
2CompletedTreatmentHodgkins Disease (HD) / Human Immunodeficiency Virus (HIV) Infections1
2CompletedTreatmentHodgkins Disease (HD) / Lymphoma, Hodgkin Disease / Lymphoma, Hodgkins / Malignant Lymphomas1
2CompletedTreatmentHodgkins Disease (HD) / Pediatric1
2CompletedTreatmentIntraluminal Pulmonary Vein Stenosis1
2CompletedTreatmentLymphoma, Hodgkins1
2CompletedTreatmentMalignant Lymphomas9
2CompletedTreatmentMelanoma / Skin Cancers1
2CompletedTreatmentNeurofibromatosis Type 1 / Precancerous Conditions1
2CompletedTreatmentProstate Cancer1
2CompletedTreatmentRenal Cell Adenocarcinoma1
2CompletedTreatmentSarcomas1
2Not Yet RecruitingTreatmentAdvanced Hodgkin's Lymphoma1
2Not Yet RecruitingTreatmentClassical Hodgkin Lymphoma1
2RecruitingTreatmentAnn Arbor Stage I Hodgkin Lymphoma / Ann Arbor Stage I Lymphocyte-Depleted Classic Hodgkin Lymphoma / Ann Arbor Stage I Mixed Cellularity Classic Hodgkin Lymphoma / Ann Arbor Stage I Nodular Sclerosis Classic Hodgkin Lymphoma / Ann Arbor Stage IA Hodgkin Lymphoma / Ann Arbor Stage IB Hodgkin Lymphoma / Ann Arbor Stage II Hodgkin Lymphoma / Ann Arbor Stage II Lymphocyte-Depleted Classic Hodgkin Lymphoma / Ann Arbor Stage II Mixed Cellularity Classic Hodgkin Lymphoma / Ann Arbor Stage II Nodular Sclerosis Classic Hodgkin Lymphoma / Ann Arbor Stage IIA Hodgkin Lymphoma / Ann Arbor Stage IIB Hodgkin Lymphoma / Classic Hodgkin Lymphoma / Lymphocyte-Rich Classic Hodgkin Lymphoma1
2RecruitingTreatmentAnn Arbor Stage I Hodgkin Lymphoma / Ann Arbor Stage IA Hodgkin Lymphoma / Ann Arbor Stage IB Hodgkin Lymphoma / Ann Arbor Stage II Hodgkin Lymphoma / Ann Arbor Stage IIA Hodgkin Lymphoma / Ann Arbor Stage IIB Hodgkin Lymphoma / Stage I Hodgkin Lymphoma / Stage IA Hodgkin Lymphoma / Stage IB Hodgkin Lymphoma / Stage II Hodgkin Lymphoma / Stage IIA Hodgkin Lymphoma / Stage IIB Hodgkin Lymphoma1
2RecruitingTreatmentBladder Cancers1
2RecruitingTreatmentClassical Hodgkin Lymphoma1
2RecruitingTreatmentClassical Hodgkin Lymphoma / Hodgkin Lymphoma (Category) / Hodgkins Disease (HD) / Lymphoma, Hodgkins1
2RecruitingTreatmentClassical Hodgkin Lymphoma / Lymphocyte-Depleted Classical Hodgkin Lymphoma / Lymphocyte-Rich Classical Hodgkin Lymphoma / Mixed Cellularity Classical Hodgkin Lymphoma / Nodular Sclerosis Classical Hodgkin Lymphoma1
2RecruitingTreatmentCoexisting Medical Conditions / Lymphoma, Hodgkins1
2RecruitingTreatmentLow Grade Glioma (LGG)1
2RecruitingTreatmentLymphoma, Hodgkins2
2RecruitingTreatmentMetastatic Breast Cancer (MBC)1
2RecruitingTreatmentRecurrent B-Cell Childhood Acute Lymphoblastic Leukemia / Recurrent Childhood B-Lymphoblastic Lymphoma1
2RecruitingTreatmentRecurrent Low-grade Gliomas / Refractory Low-grade Gliomas1
2RecruitingTreatmentTumors, Solid1
2RecruitingTreatmentUrothelial Carcinoma of the Bladder1
2TerminatedTreatmentBladder Cancers3
2TerminatedTreatmentHodgkins Disease (HD)1
2TerminatedTreatmentLymphoma, Hodgkins1
2TerminatedTreatmentMalignant Lymphomas1
2TerminatedTreatmentMelanoma1
2TerminatedTreatmentMetastatic Melanoma1
2Unknown StatusDiagnosticLung Cancers1
2Unknown StatusTreatmentHIV-associated Hodgkin Lymphoma1
2Unknown StatusTreatmentHodgkins Disease (HD)1
2Unknown StatusTreatmentMalignant Lymphomas3
2Unknown StatusTreatmentMesothelioma, Malignant1
2Unknown StatusTreatmentRenal Cancers1
2WithdrawnTreatmentAnterior Urethral Cancer / Localized Transitional Cell Cancer of the Renal Pelvis and Ureter / Posterior Urethral Cancer / Recurrent Bladder Cancer / Recurrent Urethral Cancer / Regional Transitional Cell Cancer of the Renal Pelvis and Ureter / Stage III Bladder Cancer / Transitional Cell Carcinoma of the Bladder / Ureteral Cancer / Urethral Cancer Associated With Invasive Bladder Cancer1
2, 3CompletedTreatmentBladder Cancers / Transitional Cell Cancer of the Renal Pelvis and Ureter / Urethral Cancer1
2, 3RecruitingTreatmentLangerhans Cell Histiocytosis (LCH)1
3Active Not RecruitingTreatmentLymphoma, Hodgkins3
3Active Not RecruitingTreatmentMalignant Lymphomas5
3CompletedTreatmentBladder Cancers / Transitional Cell Cancer of the Renal Pelvis and Ureter / Urethral Cancer1
3CompletedTreatmentBladder Cancers / Urethral Cancer1
3CompletedTreatmentCervical Cancers1
3CompletedTreatmentElderly Patients (>65 Years) / Lymphoma, Large B-Cell, Diffuse (DLBCL)1
3CompletedTreatmentHodgkins Disease (HD)1
3CompletedTreatmentLeukemias1
3CompletedTreatmentLung Cancers3
3CompletedTreatmentLymphoma, Hodgkins4
3CompletedTreatmentMalignant Lymphomas4
3CompletedTreatmentMelanoma (Skin)2
3CompletedTreatmentMelanoma / Skin Cancers1
3CompletedTreatmentMetastatic Bladder Cancer / Stage III Bladder Cancer / Transitional Cell Carcinoma of the Bladder1
3CompletedTreatmentProstate Cancer2
3Not Yet RecruitingTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)1
3RecruitingTreatmentLangerhans Cell Histiocytosis (LCH)1
3RecruitingTreatmentLymphoma, Hodgkins1
3TerminatedTreatmentExtragonadal Germ Cell Tumor / Testicular germ cell tumour1
3TerminatedTreatmentMalignant Lymphomas1
3TerminatedTreatmentProstate Cancer1
3Unknown StatusTreatmentBladder Cancers1
3Unknown StatusTreatmentCancer of the Ovary / Childhood Germ Cell Tumor / Extragonadal Germ Cell Tumor1
3Unknown StatusTreatmentExtragonadal Germ Cell Tumor / Testicular germ cell tumour1
3Unknown StatusTreatmentLung Cancers3
3Unknown StatusTreatmentLymphoma, Hodgkins1
3Unknown StatusTreatmentMalignant Lymphomas2
4RecruitingTreatmentLymphoma, Hodgkins1
4RecruitingTreatmentMalignant Lymphomas1
Not AvailableActive Not RecruitingTreatmentMalignant Lymphomas1
Not AvailableCompletedTreatmentAtaxia-Telangiectasia1
Not AvailableCompletedTreatmentChildhood Langerhans Cell Histiocytosis1
Not AvailableCompletedTreatmentLymphoma, Large Cell / Non-Hodgkin's Lymphoma (NHL)1
Not AvailableRecruitingTreatmentLymphoma, Hodgkins1
Not AvailableUnknown StatusTreatmentMalignant Lymphomas2

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
FormRouteStrength
Powder, for solutionIntravenous10 mg
InjectionIntravenous1 mg/1mL
Injection, powder, lyophilized, for solutionIntravenous10 mg/10mL
LiquidIntravenous1 mg
SolutionIntravenous1 mg
Prices
Unit descriptionCostUnit
Vinblastine sulf 10 mg vial18.6USD each
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)267 °CNot Available
water solubilityNegligibleNot Available
logP3.70SANGSTER (1994)
Predicted Properties
PropertyValueSource
Water Solubility0.0169 mg/mLALOGPS
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 Å2ChemAxon
Rotatable Bond Count10ChemAxon
Refractivity222.42 m3·mol-1ChemAxon
Polarizability87.81 Å3ChemAxon
Number of Rings9ChemAxon
Bioavailability1ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9806
Blood Brain Barrier-0.9203
Caco-2 permeable+0.6283
P-glycoprotein substrateSubstrate0.9213
P-glycoprotein inhibitor IInhibitor0.7737
P-glycoprotein inhibitor IIInhibitor0.6817
Renal organic cation transporterNon-inhibitor0.771
CYP450 2C9 substrateNon-substrate0.816
CYP450 2D6 substrateNon-substrate0.9117
CYP450 3A4 substrateSubstrate0.72
CYP450 1A2 substrateNon-inhibitor0.9198
CYP450 2C9 inhibitorNon-inhibitor0.9093
CYP450 2D6 inhibitorNon-inhibitor0.9231
CYP450 2C19 inhibitorNon-inhibitor0.9025
CYP450 3A4 inhibitorNon-inhibitor0.8149
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8681
Ames testNon AMES toxic0.9132
CarcinogenicityNon-carcinogens0.91
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.9111 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9366
hERG inhibition (predictor II)Non-inhibitor0.5793
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as vinca alkaloids. These are alkaloids with a dimeric chemical structure composed of an indole nucleus (catharanthine), and a dihydroindole nucleus (vindoline), joined together.
Kingdom
Organic compounds
Super Class
Alkaloids and derivatives
Class
Vinca alkaloids
Sub Class
Not Available
Direct Parent
Vinca alkaloids
Alternative Parents
Carbazoles / 3-alkylindoles / Tricarboxylic acids and derivatives / Anisoles / Dialkylarylamines / Alkyl aryl ethers / Aralkylamines / Piperidines / N-alkylpyrrolidines / Tertiary alcohols
show 12 more
Substituents
Vinca alkaloid skeleton / Carbazole / 3-alkylindole / Tricarboxylic acid or derivatives / Indole or derivatives / Indole / Tertiary aliphatic/aromatic amine / Dialkylarylamine / Anisole / Aralkylamine
show 30 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Adduct
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
  1. Jordan MA, Kamath K: How do microtubule-targeted drugs work? An overview. Curr Cancer Drug Targets. 2007 Dec;7(8):730-42. [PubMed:18220533]
  2. Correia JJ: Effects of antimitotic agents on tubulin-nucleotide interactions. Pharmacol Ther. 1991 Nov;52(2):127-47. [PubMed: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. [PubMed: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. [PubMed:15579115]
  5. Gupta S, Bhattacharyya B: Antimicrotubular drugs binding to vinca domain of tubulin. Mol Cell Biochem. 2003 Nov;253(1-2):41-7. [PubMed:14619954]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Adduct
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
  1. Jordan MA, Kamath K: How do microtubule-targeted drugs work? An overview. Curr Cancer Drug Targets. 2007 Dec;7(8):730-42. [PubMed:18220533]
  2. Correia JJ: Effects of antimitotic agents on tubulin-nucleotide interactions. Pharmacol Ther. 1991 Nov;52(2):127-47. [PubMed: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. [PubMed: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. [PubMed:15579115]
  5. Gupta S, Bhattacharyya B: Antimicrotubular drugs binding to vinca domain of tubulin. Mol Cell Biochem. 2003 Nov;253(1-2):41-7. [PubMed:14619954]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Adduct
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
  1. Jordan MA, Kamath K: How do microtubule-targeted drugs work? An overview. Curr Cancer Drug Targets. 2007 Dec;7(8):730-42. [PubMed:18220533]
  2. Correia JJ: Effects of antimitotic agents on tubulin-nucleotide interactions. Pharmacol Ther. 1991 Nov;52(2):127-47. [PubMed: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. [PubMed: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. [PubMed:15579115]
  5. Gupta S, Bhattacharyya B: Antimicrotubular drugs binding to vinca domain of tubulin. Mol Cell Biochem. 2003 Nov;253(1-2):41-7. [PubMed:14619954]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Adduct
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
  1. Jordan MA, Kamath K: How do microtubule-targeted drugs work? An overview. Curr Cancer Drug Targets. 2007 Dec;7(8):730-42. [PubMed:18220533]
  2. Correia JJ: Effects of antimitotic agents on tubulin-nucleotide interactions. Pharmacol Ther. 1991 Nov;52(2):127-47. [PubMed: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. [PubMed: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. [PubMed:15579115]
  5. Gupta S, Bhattacharyya B: Antimicrotubular drugs binding to vinca domain of tubulin. Mol Cell Biochem. 2003 Nov;253(1-2):41-7. [PubMed:14619954]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Adduct
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
  1. Jordan MA, Kamath K: How do microtubule-targeted drugs work? An overview. Curr Cancer Drug Targets. 2007 Dec;7(8):730-42. [PubMed:18220533]
  2. Correia JJ: Effects of antimitotic agents on tubulin-nucleotide interactions. Pharmacol Ther. 1991 Nov;52(2):127-47. [PubMed: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. [PubMed: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. [PubMed:15579115]
  5. Gupta S, Bhattacharyya B: Antimicrotubular drugs binding to vinca domain of tubulin. Mol Cell Biochem. 2003 Nov;253(1-2):41-7. [PubMed:14619954]
Kind
Protein
Organism
Human
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
  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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed:17126817]

Enzymes

Details
1. Cytochrome P450 3A4
Kind
Protein
Organism
Human
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
  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. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
  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:10490933]
  3. 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. [PubMed:20959500]
  4. 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. [PubMed:11770832]
Kind
Protein
Organism
Human
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
  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. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
  2. 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. [PubMed:8258200]

Transporters

Kind
Protein
Organism
Human
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
  1. 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. [PubMed:12490309]
  2. 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. [PubMed:11405287]
  3. 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. [PubMed:11716514]
  4. 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. [PubMed:12134945]
  5. 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. [PubMed:12636153]
  6. 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. [PubMed:12699389]
  7. 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. [PubMed:1359120]
  8. 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. [PubMed:8862725]
  9. 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. [PubMed:8960059]
  10. 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. [PubMed:9655875]
  11. 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. [PubMed:9751076]
  12. 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. [PubMed:10087141]
  13. 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. [PubMed:10746169]
  14. 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. [PubMed:14985103]
  15. 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. [PubMed:15616150]
  16. 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. [PubMed:11181899]
  17. 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. [PubMed:11785684]
  18. 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. [PubMed:12604693]
  19. 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. [PubMed:12724138]
  20. 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. [PubMed:12948019]
  21. 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. [PubMed:14698039]
  22. 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. [PubMed:14706813]
  23. 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. [PubMed:8100632]
  24. 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. [PubMed:8621716]
  25. 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. [PubMed:10411602]
  26. 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. [PubMed:10617675]
  27. 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. [PubMed:14991868]
  28. 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. [PubMed:19806783]
  29. 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. [PubMed:19631272]
  30. 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. [PubMed:19530439]
  31. 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. [PubMed:19123050]
  32. 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. [PubMed:11961114]
  33. 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. [PubMed:12081145]
  34. Henning U, Loffler S, Krieger K, Klimke A: Uptake of clozapine into HL-60 promyelocytic leukaemia cells. Pharmacopsychiatry. 2002 May;35(3):90-5. [PubMed:12107852]
  35. 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. [PubMed:12134946]
  36. Yasuda K, Lan LB, Sanglard D, Furuya K, Schuetz JD, Schuetz EG: Interaction of cytochrome P450 3A inhibitors with P-glycoprotein. J Pharmacol Exp Ther. 2002 Oct;303(1):323-32. [PubMed:12235267]
Kind
Protein
Organism
Human
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
  1. 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. [PubMed:11323161]
  2. 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. [PubMed:8621644]
  3. 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. [PubMed:11834888]
  4. 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. [PubMed:16458542]
Kind
Protein
Organism
Human
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
  1. 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. [PubMed:11323161]
  2. 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. [PubMed:15616150]
  3. 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. [PubMed:2172249]
  4. 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. [PubMed:12134946]
  5. 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. [PubMed:17045309]
Kind
Protein
Organism
Human
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
  1. 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. [PubMed:12069597]
Details
5. Bile salt export pump
Kind
Protein
Organism
Human
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
  1. 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. [PubMed:12739759]
  2. 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. [PubMed:10617675]
Kind
Protein
Organism
Human
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
  1. 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. [PubMed:21861202]

Drug created on June 13, 2005 07:24 / Updated on December 18, 2018 09:09