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Record Information
Version3.6
Creation Date2012-09-06 15:16:50 UTC
Update Date2016-02-11 01:29:38 UTC
HMDB IDHMDB14710
Secondary Accession NumbersNone
Metabolite Identification
Common NameVinblastine
DescriptionVinblastine is only found in individuals that have used or taken this drug. It is an antitumor alkaloid isolated from Vinca rosea. (Merck, 11th ed.)The antitumor activity of vinblastine is thought to be due primarily to inhibition of mitosis at metaphase through its interaction with tubulin. Vinblastine binds to the microtubular proteins of the mitotic spindle, leading to crystallization of the microtubule and mitotic arrest or cell death.
Structure
Thumb
Synonyms
ValueSource
(2ALPHA,2'BETA,3BETA,4ALPHA,5BETA)-VINCALEUKOBLASTINEChEBI
VLBChEBI
(2a,2'b,3b,4a,5b)-VINCALEUKOBLASTINEGenerator
(2α,2'β,3β,4α,5β)-vincaleukoblastineGenerator
Chemical FormulaC46H58N4O9
Average Molecular Weight810.9741
Monoisotopic Molecular Weight810.420379474
IUPAC Namemethyl (1R,9R,10S,11R,12R,19R)-11-(acetyloxy)-12-ethyl-4-[(13S,15S,17S)-17-ethyl-17-hydroxy-13-(methoxycarbonyl)-1,11-diazatetracyclo[13.3.1.0⁴,¹².0⁵,¹⁰]nonadeca-4(12),5,7,9-tetraen-13-yl]-10-hydroxy-5-methoxy-8-methyl-8,16-diazapentacyclo[10.6.1.0¹,⁹.0²,⁷.0¹⁶,¹⁹]nonadeca-2(7),3,5,13-tetraene-10-carboxylate
Traditional Namevinblastine
CAS Registry Number865-21-4
SMILES
[H][C@@]12N(C)C3=C(C=C(C(OC)=C3)[C@]3(C[C@@H]4CN(C[C@](O)(CC)C4)CCC4=C3NC3=CC=CC=C43)C(=O)OC)[C@@]11CCN3CC=C[C@@](CC)([C@@H](OC(C)=O)[C@]2(O)C(=O)OC)[C@@]13[H]
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 KeyInChIKey=JXLYSJRDGCGARV-XQKSVPLYSA-N
Chemical Taxonomy
DescriptionThis 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.
KingdomOrganic compounds
Super ClassAlkaloids and derivatives
ClassVinca alkaloids
Sub ClassNot Available
Direct ParentVinca alkaloids
Alternative Parents
Substituents
  • Vinca alkaloid skeleton
  • Carbazole
  • Indole or derivatives
  • Indole
  • Dialkylarylamine
  • Anisole
  • Aralkylamine
  • Tetrahydropyridine
  • Alkyl aryl ether
  • Benzenoid
  • N-alkylpyrrolidine
  • Piperidine
  • Dicarboxylic acid or derivatives
  • Heteroaromatic compound
  • Acetate salt
  • Methyl ester
  • Tertiary alcohol
  • Pyrrolidine
  • Pyrrole
  • Cyclic alcohol
  • Tertiary aliphatic amine
  • Tertiary amine
  • Carboxylic acid ester
  • 1,2-aminoalcohol
  • Azacycle
  • Organoheterocyclic compound
  • Ether
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Amine
  • Alcohol
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Ontology
StatusExpected but not Quantified
Origin
  • Drug
Biofunction
  • Antineoplastic Agents, Phytogenic
  • Tubulin Modulators
Application
  • Pharmaceutical
Cellular locations
  • Cytoplasm
  • Membrane
Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting Point267 °CNot Available
Boiling PointNot AvailableNot Available
Water Solubility1.69e-02 g/LNot Available
LogP3.9Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.017 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
Polarizability87.3 Å3ChemAxon
Number of Rings9ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
SpectraNot Available
Biological Properties
Cellular Locations
  • Cytoplasm
  • Membrane
Biofluid Locations
  • Blood
  • Urine
Tissue LocationNot Available
Pathways
NameSMPDB LinkKEGG Link
Vinblastine PathwaySMP00436Not Available
Normal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodExpected but not QuantifiedNot ApplicableNot AvailableNot AvailableTaking drug identified by DrugBank entry DB00570
  • Not Applicable
details
UrineExpected but not QuantifiedNot ApplicableNot AvailableNot AvailableTaking drug identified by DrugBank entry DB00570
  • Not Applicable
details
Abnormal Concentrations
Not Available
Predicted Concentrations
BiofluidValueOriginal ageOriginal sexOriginal conditionComments
Blood0-1 uMAdult (>18 years old)BothNormalPredicted based on drug qualities
Blood0-1 umol/mmol creatinineAdult (>18 years old)BothNormalPredicted based on drug qualities
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDDB00570
DrugBank Metabolite IDNot Available
Phenol Explorer Compound IDNot Available
Phenol Explorer Metabolite IDNot Available
FoodDB IDNot Available
KNApSAcK IDNot Available
Chemspider ID211446
KEGG Compound IDC07201
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkVinblastine
NuGOwiki LinkHMDB14710
Metagene LinkHMDB14710
METLIN IDNot Available
PubChem Compound241903
PDB IDNot Available
ChEBI ID27375
References
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Not Available
General References
  1. Starling D: Two ultrastructurally distinct tubulin paracrystals induced in sea-urchin eggs by vinblastine sulphate. J Cell Sci. 1976 Jan;20(1):79-89. [942954 ]

Enzymes

General function:
Involved in monooxygenase 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 reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Acts as a 1,8-cineole 2-exo-monooxygenase. The enzyme also hydroxylates etoposide.
Gene Name:
CYP3A4
Uniprot ID:
P08684
Molecular weight:
57255.585
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. Epub 2009 Nov 24. [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. [10490933 ]
General function:
Involved in monooxygenase 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 antidepressants.
Gene Name:
CYP2D6
Uniprot ID:
P10635
Molecular weight:
55768.94
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. Epub 2009 Nov 24. [19934256 ]
General function:
Involved in sequence-specific DNA binding transcription factor activity
Specific function:
Transcription factor that recognizes and binds to the enhancer heptamer motif 5'-TGA[CG]TCA-3'
Gene Name:
JUN
Uniprot ID:
P05412
Molecular weight:
35675.3
References
  1. Brantley-Finley C, Lyle CS, Du L, Goodwin ME, Hall T, Szwedo D, Kaushal GP, Chambers TC: The JNK, ERK and p53 pathways play distinct roles in apoptosis mediated by the antitumor agents vinblastine, doxorubicin, and etoposide. Biochem Pharmacol. 2003 Aug 1;66(3):459-69. [12907245 ]
  2. Bene A, Kurten RC, Chambers TC: Subcellular localization as a limiting factor for utilization of decoy oligonucleotides. Nucleic Acids Res. 2004 Oct 21;32(19):e142. [15498923 ]
  3. Obey TB, Lyle CS, Chambers TC: Role of c-Jun in cellular sensitivity to the microtubule inhibitor vinblastine. Biochem Biophys Res Commun. 2005 Oct 7;335(4):1179-84. [16111654 ]
  4. Martinez-Campa C, Casado P, Rodriguez R, Zuazua P, Garcia-Pedrero JM, Lazo PS, Ramos S: Effect of vinca alkaloids on ERalpha levels and estradiol-induced responses in MCF-7 cells. Breast Cancer Res Treat. 2006 Jul;98(1):81-9. Epub 2006 Mar 23. [16555127 ]
  5. Duan L, Sterba K, Kolomeichuk S, Kim H, Brown PH, Chambers TC: Inducible overexpression of c-Jun in MCF7 cells causes resistance to vinblastine via inhibition of drug-induced apoptosis and senescence at a step subsequent to mitotic arrest. Biochem Pharmacol. 2007 Feb 15;73(4):481-90. Epub 2006 Oct 29. [17126817 ]
General function:
Involved in structural molecule activity
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:
49670.5
References
  1. Jordan MA, Kamath K: How do microtubule-targeted drugs work? An overview. Curr Cancer Drug Targets. 2007 Dec;7(8):730-42. [18220533 ]
  2. Correia JJ: Effects of antimitotic agents on tubulin-nucleotide interactions. Pharmacol Ther. 1991 Nov;52(2):127-47. [1818332 ]
  3. Jordan A, Hadfield JA, Lawrence NJ, McGown AT: Tubulin as a target for anticancer drugs: agents which interact with the mitotic spindle. Med Res Rev. 1998 Jul;18(4):259-96. [9664292 ]
  4. Islam MN, Iskander MN: Microtubulin binding sites as target for developing anticancer agents. Mini Rev Med Chem. 2004 Dec;4(10):1077-104. [15579115 ]
  5. Gupta S, Bhattacharyya B: Antimicrotubular drugs binding to vinca domain of tubulin. Mol Cell Biochem. 2003 Nov;253(1-2):41-7. [14619954 ]
General function:
Involved in structural molecule activity
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:
TUBA1A
Uniprot ID:
Q71U36
Molecular weight:
50135.2
References
  1. Jordan MA, Kamath K: How do microtubule-targeted drugs work? An overview. Curr Cancer Drug Targets. 2007 Dec;7(8):730-42. [18220533 ]
  2. Correia JJ: Effects of antimitotic agents on tubulin-nucleotide interactions. Pharmacol Ther. 1991 Nov;52(2):127-47. [1818332 ]
  3. Jordan A, Hadfield JA, Lawrence NJ, McGown AT: Tubulin as a target for anticancer drugs: agents which interact with the mitotic spindle. Med Res Rev. 1998 Jul;18(4):259-96. [9664292 ]
  4. Islam MN, Iskander MN: Microtubulin binding sites as target for developing anticancer agents. Mini Rev Med Chem. 2004 Dec;4(10):1077-104. [15579115 ]
  5. Gupta S, Bhattacharyya B: Antimicrotubular drugs binding to vinca domain of tubulin. Mol Cell Biochem. 2003 Nov;253(1-2):41-7. [14619954 ]

Transporters

General function:
Involved in ATP binding
Specific function:
Mediates hepatobiliary excretion of numerous organic anions. May function as a cellular cisplatin transporter
Gene Name:
ABCC2
Uniprot ID:
Q92887
Molecular weight:
174205.6
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. [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. [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. [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. [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. [17045309 ]
General function:
Involved in ATP binding
Specific function:
Mediates export of organic anions and drugs from the cytoplasm. Mediates ATP-dependent transport of glutathione and glutathione conjugates, leukotriene C4, estradiol-17-beta-o- glucuronide, methotrexate, antiviral drugs and other xenobiotics. Confers resistance to anticancer drugs. Hydrolyzes ATP with low efficiency
Gene Name:
ABCC1
Uniprot ID:
P33527
Molecular weight:
171589.5
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. [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. [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. [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. [16458542 ]
General function:
Involved in ATP binding
Specific function:
May participate directly in the active transport of drugs into subcellular organelles or influence drug distribution indirectly. Transports glutathione conjugates as leukotriene-c4 (LTC4) and N-ethylmaleimide S-glutathione (NEM-GS)
Gene Name:
ABCC6
Uniprot ID:
O95255
Molecular weight:
164904.8
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. [12069597 ]
General function:
Involved in ATP binding
Specific function:
Involved in the ATP-dependent secretion of bile salts into the canaliculus of hepatocytes
Gene Name:
ABCB11
Uniprot ID:
O95342
Molecular weight:
146405.8
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. [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. [10617675 ]
General function:
Involved in ATP binding
Specific function:
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells
Gene Name:
ABCB1
Uniprot ID:
P08183
Molecular weight:
141477.3
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. [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. [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. [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. [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. [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. [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. [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. [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. [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. [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. [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. [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. [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. [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. [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. [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. [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. [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. [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. [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. [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. [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. [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. [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. [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. [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. [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. [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. Epub 2009 Jul 21. [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. [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. Epub 2009 Jan 4. [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. [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. [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. [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. [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. [12235267 ]
General function:
Involved in ion transmembrane transporter activity
Specific function:
Mediates tubular uptake of organic compounds from circulation. Mediates the influx of agmatine, dopamine, noradrenaline (norepinephrine), serotonin, choline, famotidine, ranitidine, histamin, creatinine, amantadine, memantine, acriflavine, 4-[4-(dimethylamino)-styryl]-N-methylpyridinium ASP, amiloride, metformin, N-1-methylnicotinamide (NMN), tetraethylammonium (TEA), 1-methyl-4-phenylpyridinium (MPP), cimetidine, cisplatin and oxaliplatin. Cisplatin may develop a nephrotoxic action. Transport of creatinine is inhibited by fluoroquinolones such as DX-619 and LVFX. This transporter is a major determinant of the anticancer activity of oxaliplatin and may contribute to antitumor specificity
Gene Name:
SLC22A2
Uniprot ID:
O15244
Molecular weight:
62564.0
References
  1. Pan BF, Sweet DH, Pritchard JB, Chen R, Nelson JA: A transfected cell model for the renal toxin transporter, rOCT2. Toxicol Sci. 1999 Feb;47(2):181-6. [10220855 ]