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Identification
Name Vincristine
Accession Number DB00541 (APRD00495)
Type small molecule
Groups approved
Description

Antitumor alkaloid isolated from Vinca Rosea. (Merck, 11th ed.)
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
22-Oxovincaleukoblastine
Indole alkaloid
LCR
Leurocristine
VCR
VIN
Vincristina [DCIT]
Vincristine Sulfate
Vincristinum [INN-Latin]
Vincrstine
Vincrystine
Z-D-Val-Lys(Z)-OH
First Prev Next Last
Salts Not Available
Brand names
Name Company
Marqibo
Onco TCS
Oncovin
Vincasar
Vincasar PFS
Vincrex
Vincristine Sulfate PFS
Vinkristin
Brand mixtures Not Available
Categories
  • Antineoplastic Agents
  • Antineoplastic Agents, Phytogenic
  • Tubulin Modulators
CAS number 57-22-7
Weight Average: 824.9576
Monoisotopic: 824.399644032
Chemical Formula C46H56N4O10
InChI Key InChIKey=OGWKCGZFUXNPDA-XQKSVPLYSA-N
InChI
InChI=1S/C46H56N4O10/c1-7-42(55)22-28-23-45(40(53)58-5,36-30(14-18-48(24-28)25-42)29-12-9-10-13-33(29)47-36)32-20-31-34(21-35(32)57-4)50(26-51)38-44(31)16-19-49-17-11-15-43(8-2,37(44)49)39(60-27(3)52)46(38,56)41(54)59-6/h9-13,15,20-21,26,28,37-39,47,55-56H,7-8,14,16-19,22-25H2,1-6H3/t28-,37+,38-,39-,42+,43-,44-,45+,46+/m1/s1
Plain Text
IUPAC Name
methyl (1R,9R,10S,11R,12R,19R)-11-(acetyloxy)-12-ethyl-4-[(13S,15S,17S)-17-ethyl-17-hydroxy-13-(methoxycarbonyl)-1,11-diazatetracyclo[13.3.1.0^{4,12}.0^{5,10}]nonadeca-4(12),5,7,9-tetraen-13-yl]-8-formyl-10-hydroxy-5-methoxy-8,16-diazapentacyclo[10.6.1.0^{1,9}.0^{2,7}.0^{16,19}]nonadeca-2(7),3,5,13-tetraene-10-carboxylate
SMILES
[H][C@@]12N3CC[C@@]11C4=CC(=C(OC)C=C4N(C=O)[C@@]1([H])[C@](O)([C@H](OC(C)=O)[C@]2(CC)C=CC3)C(=O)OC)[C@]1(C[C@]2([H])CN(C[C@](O)(CC)C2)CCC2=C1NC1=CC=CC=C21)C(=O)OC
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Tryptamines and Derivatives
Substructures
  • Carbonyl Compounds
  • Carboxylic Acids and Derivatives
  • Glycerol and Derivatives
  • Hydroxy Compounds
  • Alkanes and Alkenes
  • Acetates
  • Indoles and Indole Derivatives
  • Phenols and Derivatives
  • Pyrroles
  • Phenylacetates
  • Short-chain Hydroxy Acids
  • Pyrrolidines
  • Ethers
  • Benzene and Derivatives
  • Aliphatic and Aryl Amines
  • Alcohols and Polyols
  • Phenethylamines
  • Heterocyclic compounds
  • Aromatic compounds
  • Anisoles
  • Phenylpropylamines
  • Tryptamines and Derivatives
  • Imines
  • Phenyl Esters
  • Anilines
  • Amphetamines
  • Piperidines
  • Pyrrolines
Pharmacology
Indication For treatment of acute leukaemia, malignant lymphoma, Hodgkin's disease, acute erythraemia, acute panmyelosis
Pharmacodynamics Vincristine is a vinca alkaloid antineoplastic agent used as a treatment for various cancers including breast cancer, Hodgkin's disease, Kaposi's sarcoma, and testicular cancer. 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. Vincristine binds to the microtubular proteins of the mitotic spindle, leading to crystallization of the microtubule and mitotic arrest or cell death. Vincristine has some immunosuppressant effect. The vinca alkaloids are considered to be cell cycle phase-specific.
Mechanism of action The antitumor activity of Vincristine is thought to be due primarily to inhibition of mitosis at metaphase through its interaction with tubulin. Like other vinca alkaloids, Vincristine may also interfere with: 1) amino acid, cyclic AMP, and glutathione metabolism, 2) calmodulin-dependent Ca2+-transport ATPase activity, 3) cellular respiration, and 4) nucleic acid and lipid biosynthesis.
Absorption Not Available
Volume of distribution Not Available
Protein binding ~75%
Metabolism Hepatic
Route of elimination Not Available
Half life 19-155 hours
Clearance Not Available
Toxicity IVN-RAT LD50 1300 mg/kg; IPR-MUS LD50 5.2 mg/kg
Affected organisms
  • Humans and other mammals
Pathways
Pathway Name SMPDB ID
Smp00437 Vincristine Pathway SMP00437
Pharmacoeconomics
Manufacturers
  • Eli lilly and co
  • Teva parenteral medicines inc
  • Bristol myers squibb
  • Abic ltd
  • Abraxis pharmaceutical products
  • App pharmaceuticals llc
  • Hospira inc
Packagers
Dosage forms
Form Route Strength
Liquid Intravenous
Solution Intravenous
Prices
Unit description Cost Unit
Vincristine 2 mg/2 ml vial 18.06 USD ml
Oncovite tablet 0.19 USD tablet
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 220 °C PhysProp
logP 2.82 HANSCH,C ET AL. (1995)
pKa 5 MERCK INDEX (1996)
Predicted Properties
Property Value Source
water solubility 3.00e-02 g/l ALOGPS
logP 3.36 ALOGPS
logP 3.13 ChemAxon
logS -4.4 ALOGPS
pKa (strongest acidic) 10.85 ChemAxon
pKa (strongest basic) 8.66 ChemAxon
physiological charge 2 ChemAxon
hydrogen acceptor count 9 ChemAxon
hydrogen donor count 3 ChemAxon
polar surface area 171.17 ChemAxon
rotatable bond count 10 ChemAxon
refractivity 221.48 ChemAxon
polarizability 88.59 ChemAxon
References
Synthesis Reference Not Available
General Reference
  1. Graf WD, Chance PF, Lensch MW, Eng LJ, Lipe HP, Bird TD: Severe vincristine neuropathy in Charcot-Marie-Tooth disease type 1A. Cancer. 1996 Apr 1;77(7):1356-62. Pubmed
  2. Qweider M, Gilsbach JM, Rohde V: Inadvertent intrathecal vincristine administration: a neurosurgical emergency. Case report. J Neurosurg Spine. 2007 Mar;6(3):280-3. Pubmed
  3. JOHNSON IS, ARMSTRONG JG, GORMAN M, BURNETT JP Jr: THE VINCA ALKALOIDS: A NEW CLASS OF ONCOLYTIC AGENTS. Cancer Res. 1963 Sep;23:1390-427. Pubmed
External Links
Resource Link
KEGG Compound C07204 Link_out
PubChem Compound 5978 Link_out
PubChem Substance 46507033 Link_out
ChemSpider 5758 Link_out
ChEBI 28445 Link_out
ChEMBL 28445 Link_out
Therapeutic Targets Database DAP000114 Link_out
PharmGKB PA451879 Link_out
Drug Product Database 2143305 Link_out
RxList http://www.rxlist.com/cgi/generic3/vincristine.htm Link_out
Drugs.com http://www.drugs.com/cdi/vincristine.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Vincristine Link_out
ATC Codes
  • L01CA02
AHFS Codes
  • 10:00.00
PDB Entries
FDA label Not Available
MSDS show (73.5 KB)
Interactions
Drug Interactions
Drug Interaction
Amprenavir Amprenavir, a strong CYP3A4 inhibitor, may increase the serum concentration of Vincristine by decreasing its metabolism. Consider alternate therapy to avoid Vincristine toxicity. Monitor for changes in the therapeutic and adverse effects of Vincristine if Amprenavir is initiated, discontinued or dose changed.
Aprepitant Aprepitant may change levels of the chemotherapy agent, vincristine.
Atazanavir Atazanavir, a strong CYP3A4 inhibitor, may increase the serum concentration of Vincristine by decreasing its metabolism. Consider alternate therapy to avoid Vincristine toxicity. Monitor for changes in the therapeutic and adverse effects of Vincristine if Atazanavir is initiated, discontinued or dose changed.
Clarithromycin Clarithromycin, a CYP3A4 and p-glycoprotein inhibitor, may increase the Vincristine serum concentration and distribution in certain cells. Consider alternate therapy to avoid Vincristine toxicity. Monitor for changes in the therapeutic and adverse effects of Vincristine if Clarithromycin is initiated, discontinued or dose changed.
Conivaptan Conivaptan, a strong CYP3A4 inhibitor, may increase the serum concentration of Vincristine by decreasing its metabolism. Consider alternate therapy to avoid Vincristine toxicity. Monitor for changes in the therapeutic and adverse effects of Vincristine if Conivaptan is initiated, discontinued or dose changed.
Darunavir Darunavir, a strong CYP3A4 inhibitor, may increase the serum concentration of Vincristine by decreasing its metabolism. Consider alternate therapy to avoid Vincristine toxicity. Monitor for changes in the therapeutic and adverse effects of Vincristine if Darunavir is initiated, discontinued or dose changed.
Delavirdine Delavirdine, a strong CYP3A4 inhibitor, may increase the serum concentration of Vincristine by decreasing its metabolism. Consider alternate therapy to avoid Vincristine toxicity. Monitor for changes in the therapeutic and adverse effects of Vincristine if Delavirdine is initiated, discontinued or dose changed.
Digoxin The antineoplasic agent decreases the effect of digoxin
Dirithromycin Dirithromycin, a CYP3A4 and p-glycoprotein inhibitor, may increase the Vincristine serum concentration and distribution in certain cells. Consider alternate therapy to avoid Vincristine toxicity. Monitor for changes in the therapeutic and adverse effects of Vincristine if Dirithromycin is initiated, discontinued or dose changed.
Erythromycin Erythromycin, a CYP3A4 and p-glycoprotein inhibitor, may increase the Vincristine serum concentration and distribution in certain cells. Consider alternate therapy to avoid Vincristine toxicity. Monitor for changes in the therapeutic and adverse effects of Vincristine if Erythromycin is initiated, discontinued or dose changed.
Fluconazole Increases the effect and toxicity of anticancer agent
Fosamprenavir Fosamprenavir, a strong CYP3A4 inhibitor, may increase the serum concentration of Vincristine by decreasing its metabolism. Consider alternate therapy to avoid Vincristine toxicity. Monitor for changes in the therapeutic and adverse effects of Vincristine if Fosamprenavir is initiated, discontinued or dose changed.
Imatinib Imatinib, a strong CYP3A4 inhibitor, may increase the serum concentration of Vincristine by decreasing its metabolism. Consider alternate therapy to avoid Vincristine toxicity. Monitor for changes in the therapeutic and adverse effects of Vincristine if Imatinib is initiated, discontinued or dose changed.
Indinavir Indinavir, a strong CYP3A4 inhibitor, may increase the serum concentration of Vincristine by decreasing its metabolism. Consider alternate therapy to avoid Vincristine toxicity. Monitor for changes in the therapeutic and adverse effects of Vincristine if Indinavir is initiated, discontinued or dose changed.
Isoniazid Isoniazid, a strong CYP3A4 inhibitor, may increase the serum concentration of Vincristine by decreasing its metabolism. Consider alternate therapy to avoid Vincristine toxicity. Monitor for changes in the therapeutic and adverse effects of Vincristine if Isoniazid is initiated, discontinued or dose changed.
Itraconazole Itraconazole, a strong CYP3A4 and p-glycoprotein inhibitor, may increase the serum concentration of Vincristine by decreasing its metabolism and/or increasing efflux. Consider alternate therapy to avoid Vincristine toxicity. Monitor for changes in the therapeutic and adverse effects of Vincristine if Itraconazole is initiated, discontinued or dose changed.
Ketoconazole Ketoconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of Vincristine by decreasing its metabolism. Consider alternate therapy to avoid Vincristine toxicity. Monitor for changes in the therapeutic and adverse effects of Vincristine if Ketoconazole is initiated, discontinued or dose changed.
Leflunomide Vincristine may increase the adverse/toxic effects of Leflunomide. This may increase the risk of hematologic toxicities such as pancytopenia, agranulocytosis and thrombocytopenia. In patients receiving Vincristine, consider eliminating the loading dose of Leflunomide. Monitor for bone marrow suppression at least monthly during concomitant therapy.
Lopinavir Lopinavir, a strong CYP3A4 and p-glycoprotein inhibitor, may increase the serum concentration of Vincristine by decreasing its metabolism and/or increasing its efflux. Consider alternate therapy to avoid Vincristine toxicity. Monitor for changes in the therapeutic and adverse effects of Vincristine if Lopinavir is initiated, discontinued or dose changed.
Miconazole Miconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of Vincristine by decreasing its metabolism. Consider alternate therapy to avoid Vincristine toxicity. Monitor for changes in the therapeutic and adverse effects of Vincristine if Miconazole is initiated, discontinued or dose changed.
Mitomycin Potentially severe lung toxicity
Natalizumab Concomitant Vincristine and Natalizumab therapy may increase the risk of infection. Concurrent therapy should be avoided.
Nefazodone Nefazodone, a strong CYP3A4 inhibitor, may increase the serum concentration of Vincristine by decreasing its metabolism. Consider alternate therapy to avoid Vincristine toxicity. Monitor for changes in the therapeutic and adverse effects of Vincristine if Nefazodone is initiated, discontinued or dose changed.
Nelfinavir Nelfinavir, a strong CYP3A4 inhibitor, may increase the serum concentration of Vincristine by decreasing its metabolism. Consider alternate therapy to avoid Vincristine toxicity. Monitor for changes in the therapeutic and adverse effects of Vincristine if Nelfinavir is initiated, discontinued or dose changed.
Nicardipine Nicardipine, a strong CYP3A4 inhibitor, may increase the serum concentration of Vincristine by decreasing its metabolism. Consider alternate therapy to avoid Vincristine toxicity. Monitor for changes in the therapeutic and adverse effects of Vincristine if Nicardipine is initiated, discontinued or dose changed.
Posaconazole Posaconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of Vincristine by decreasing its metabolism. Consider alternate therapy to avoid Vincristine toxicity. Monitor for changes in the therapeutic and adverse effects of Vincristine if Posaconazole is initiated, discontinued or dose changed.
Quinidine Quinidine, a strong CYP3A4 inhibitor, may increase the serum concentration of Vincristine by decreasing its metabolism. Consider alternate therapy to avoid Vincristine toxicity. Monitor for changes in the therapeutic and adverse effects of Vincristine if Quinidine is initiated, discontinued or dose changed.
Quinupristin This combination presents an increased risk of toxicity
Ritonavir Ritonavir, a strong CYP3A4 and p-glycoprotein inhibitor, may increase the serum concentration of Vincristine by decreasing its metabolism and/or increasing efflux. Consider alternate therapy to avoid Vincristine toxicity. Monitor for changes in the therapeutic and adverse effects of Vincristine if Ritonavir is initiated, discontinued or dose changed.
Saquinavir Saquinavir, a strong CYP3A4 inhibitor, may increase the serum concentration of Vincristine by decreasing its metabolism. Consider alternate therapy to avoid Vincristine toxicity. Monitor for changes in the therapeutic and adverse effects of Vincristine if Saquinavir is initiated, discontinued or dose changed.
Spiramycin Spiramycin, a CYP3A4 and p-glycoprotein inhibitor, may increase the Vincristine serum concentration and distribution in certain cells. Consider alternate therapy to avoid Vincristine toxicity. Monitor for changes in the therapeutic and adverse effects of Vincristine if Spiramycin is initiated, discontinued or dose changed.
Telithromycin Telithromycin, a CYP3A4 and p-glycoprotein inhibitor, may increase the Vincristine serum concentration and distribution in certain cells. Consider alternate therapy to avoid Vincristine toxicity. Monitor for changes in the therapeutic and adverse effects of Vincristine if Telithromycin is initiated, discontinued or dose changed.
Trastuzumab Trastuzumab may increase the risk of neutropenia and anemia. Monitor closely for signs and symptoms of adverse events.
Voriconazole Voriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of Vincristine by decreasing its metabolism. Consider alternate therapy to avoid Vincristine toxicity. Monitor for changes in the therapeutic and adverse effects of Vincristine if Voriconazole is initiated, discontinued or dose changed.
Food Interactions Not Available
Targets

1. Tubulin beta chain

Pharmacological action: yes
Actions: inhibitor

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

Organism class: human
UniProt ID: P07437 Link_out
Gene: TUBB Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
  3. Kurtzberg LS, Roth SD, Bagley RG, Rouleau C, Yao M, Crawford JL, Krumbholz RD, Schmid SM, Teicher BA: Bone marrow CFU-GM and human tumor xenograft efficacy of three tubulin binding agents. Cancer Chemother Pharmacol. 2009 Oct;64(5):1029-38. Epub 2009 Mar 10. Pubmed
  4. Gan PP, McCarroll JA, Po’uha ST, Kamath K, Jordan MA, Kavallaris M: Microtubule dynamics, mitotic arrest, and apoptosis: drug-induced differential effects of betaIII-tubulin. Mol Cancer Ther. 2010 May;9(5):1339-48. Epub 2010 May 4. Pubmed

2. Tubulin alpha-1 chain

Pharmacological action: unknown
Actions: inhibitor

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

Organism class: human
UniProt ID: P68366 Link_out
Gene: TUBA4A Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Yasui M, Koyama N, Koizumi T, Senda-Murata K, Takashima Y, Hayashi M, Sugimoto K, Honma M: Live cell imaging of micronucleus formation and development. Mutat Res. 2010 Oct 13;692(1-2):12-8. Epub 2010 Aug 5. Pubmed
  2. Gan PP, McCarroll JA, Po’uha ST, Kamath K, Jordan MA, Kavallaris M: Microtubule dynamics, mitotic arrest, and apoptosis: drug-induced differential effects of betaIII-tubulin. Mol Cancer Ther. 2010 May;9(5):1339-48. Epub 2010 May 4. Pubmed
  3. Vilpo JA, Koski T, Vilpo LM: Selective toxicity of vincristine against chronic lymphocytic leukemia cells in vitro. Eur J Haematol. 2000 Dec;65(6):370-8. Pubmed
Enzymes

1. Cytochrome P450 3A5

Actions: substrate

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics

UniProt ID: P20815 Link_out
Gene: CYP3A5 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  2. 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. Pubmed

2. Cytochrome P450 3A7

Actions: substrate

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics

UniProt ID: P24462 Link_out
Gene: CYP3A7 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.

3. Cytochrome P450 3A4

Actions: substrate, inhibitor

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. The enzyme also hydroxylates etoposide

UniProt ID: P08684 Link_out
Gene: CYP3A4
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  2. 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. Pubmed
Transporters

1. Multidrug resistance protein 1

Actions: substrate, inhibitor, inducer

Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells

UniProt ID: P08183 Link_out
Gene: ABCB1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
  2. Polli JW, Wring SA, Humphreys JE, Huang L, Morgan JB, Webster LO, Serabjit-Singh CS: Rational use of in vitro P-glycoprotein assays in drug discovery. J Pharmacol Exp Ther. 2001 Nov;299(2):620-8. Pubmed
  3. 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
  4. Doppenschmitt S, Langguth P, Regardh CG, Andersson TB, Hilgendorf C, Spahn-Langguth H: Characterization of binding properties to human P-glycoprotein: development of a [3H]verapamil radioligand-binding assay. J Pharmacol Exp Ther. 1999 Jan;288(1):348-57. Pubmed
  5. 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
  6. Li D, Jang SH, Kim J, Wientjes MG, Au JL: Enhanced drug-induced apoptosis associated with P-glycoprotein overexpression is specific to antimicrotubule agents. Pharm Res. 2003 Jan;20(1):45-50. Pubmed
  7. 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
  8. Kuo CC, Hsieh HP, Pan WY, Chen CP, Liou JP, Lee SJ, Chang YL, Chen LT, Chen CT, Chang JY: BPR0L075, a novel synthetic indole compound with antimitotic activity in human cancer cells, exerts effective antitumoral activity in vivo. Cancer Res. 2004 Jul 1;64(13):4621-8. Pubmed
  9. 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. Pubmed
  10. Tiwari AK, Sodani K, Wang SR, Kuang YH, Ashby CR Jr, Chen X, Chen ZS: Nilotinib (AMN107, Tasigna) reverses multidrug resistance by inhibiting the activity of the ABCB1/Pgp and ABCG2/BCRP/MXR transporters. Biochem Pharmacol. 2009 Jul 15;78(2):153-61. Epub 2009 Apr 11. Pubmed
  11. Noguchi K, Kawahara H, Kaji A, Katayama K, Mitsuhashi J, Sugimoto Y: Substrate-dependent bidirectional modulation of P-glycoprotein-mediated drug resistance by erlotinib. Cancer Sci. 2009 Sep;100(9):1701-7. Epub 2009 May 12. Pubmed

2. Canalicular multispecific organic anion transporter 2

Actions: inhibitor

May act as an inducible transporter in the biliary and intestinal excretion of organic anions

UniProt ID: O15438 Link_out
Gene: ABCC3 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Zeng H, Chen ZS, Belinsky MG, Rea PA, Kruh GD: Transport of methotrexate (MTX) and folates by multidrug resistance protein (MRP) 3 and MRP1: effect of polyglutamylation on MTX transport. Cancer Res. 2001 Oct 1;61(19):7225-32. Pubmed

3. Solute carrier family 22 member 3

Actions: inhibitor

Mediates potential-dependent transport of a variety of organic cations. May play a significant role in the disposition of cationic neurotoxins and neurotransmitters in the brain

UniProt ID: O75751 Link_out
Gene: SLC22A3 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Shnitsar V, Eckardt R, Gupta S, Grottker J, Muller GA, Koepsell H, Burckhardt G, Hagos Y: Expression of human organic cation transporter 3 in kidney carcinoma cell lines increases chemosensitivity to melphalan, irinotecan, and vincristine. Cancer Res. 2009 Feb 15;69(4):1494-501. Epub 2009 Feb 3. Pubmed

4. Multidrug resistance-associated protein 1

Actions: substrate, inhibitor

May participate directly in the active transport of drugs into subcellular organelles or influence drug distribution indirectly. Confers resistance to anticancer drugs. Transports LTC4. May protect milk against xenobiotics

UniProt ID: P33527 Link_out
Gene: ABCC1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. 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
  2. Godinot N, Iversen PW, Tabas L, Xia X, Williams DC, Dantzig AH, Perry WL 3rd: Cloning and functional characterization of the multidrug resistance-associated protein (MRP1/ABCC1) from the cynomolgus monkey. Mol Cancer Ther. 2003 Mar;2(3):307-16. Pubmed
  3. Nunoya K, Grant CE, Zhang D, Cole SP, Deeley RG: Molecular cloning and pharmacological characterization of rat multidrug resistance protein 1 (mrp1). Drug Metab Dispos. 2003 Aug;31(8):1016-26. Pubmed
  4. Sumizawa T, Chen ZS, Chuman Y, Seto K, Furukawa T, Haraguchi M, Tani A, Shudo N, Akiyama SI: Reversal of multidrug resistance-associated protein-mediated drug resistance by the pyridine analog PAK-104P. Mol Pharmacol. 1997 Mar;51(3):399-405. Pubmed
  5. Renes J, de Vries EG, Nienhuis EF, Jansen PL, Muller M: ATP- and glutathione-dependent transport of chemotherapeutic drugs by the multidrug resistance protein MRP1. Br J Pharmacol. 1999 Feb;126(3):681-8. Pubmed
  6. Stride BD, Grant CE, Loe DW, Hipfner DR, Cole SP, Deeley RG: Pharmacological characterization of the murine and human orthologs of multidrug-resistance protein in transfected human embryonic kidney cells. Mol Pharmacol. 1997 Sep;52(3):344-53. Pubmed

5. Multidrug resistance-associated protein 7

Actions: substrate, inhibitor

ATP-dependent transporter probably involved in cellular detoxification through lipophilic anion extrusion

UniProt ID: Q5T3U5 Link_out
Gene: ABCC10 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Chen ZS, Hopper-Borge E, Belinsky MG, Shchaveleva I, Kotova E, Kruh GD: Characterization of the transport properties of human multidrug resistance protein 7 (MRP7, ABCC10). Mol Pharmacol. 2003 Feb;63(2):351-8. Pubmed
  2. Hopper-Borge E, Xu X, Shen T, Shi Z, Chen ZS, Kruh GD: Human multidrug resistance protein 7 (ABCC10) is a resistance factor for nucleoside analogues and epothilone B. Cancer Res. 2009 Jan 1;69(1):178-84. Pubmed

6. Canalicular multispecific organic anion transporter 1

Actions: substrate, inhibitor

Mediates hepatobiliary excretion of numerous organic anions. May function as a cellular cisplatin transporter

UniProt ID: Q92887 Link_out
Gene: ABCC2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. 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
  2. Hong J, Lambert JD, Lee SH, Sinko PJ, Yang CS: Involvement of multidrug resistance-associated proteins in regulating cellular levels of (-)-epigallocatechin-3-gallate and its methyl metabolites. Biochem Biophys Res Commun. 2003 Oct 10;310(1):222-7. Pubmed
  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
  4. Chen ZS, Kawabe T, Ono M, Aoki S, Sumizawa T, Furukawa T, Uchiumi T, Wada M, Kuwano M, Akiyama SI: Effect of multidrug resistance-reversing agents on transporting activity of human canalicular multispecific organic anion transporter. Mol Pharmacol. 1999 Dec;56(6):1219-28. Pubmed

7. Bile salt export pump

Actions: substrate

Involved in the ATP-dependent secretion of bile salts into the canaliculus of hepatocytes

UniProt ID: O95342 Link_out
Gene: ABCB11 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. 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

8. ATP-binding cassette sub-family G member 2

Actions: substrate

Xenobiotic transporter that may play an important role in the exclusion of xenobiotics from the brain. May be involved in brain-to-blood efflux. Appears to play a major role in the multidrug resistance phenotype of several cancer cell lines. When overexpressed, the transfected cells become resistant to mitoxantrone, daunorubicin and doxorubicin, display diminished intracellular accumulation of daunorubicin, and manifest an ATP- dependent increase in the efflux of rhodamine 123

UniProt ID: Q9UNQ0 Link_out
Gene: ABCG2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Allen JD, Van Dort SC, Buitelaar M, van Tellingen O, Schinkel AH: Mouse breast cancer resistance protein (Bcrp1/Abcg2) mediates etoposide resistance and transport, but etoposide oral availability is limited primarily by P-glycoprotein. Cancer Res. 2003 Mar 15;63(6):1339-44. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on February 08, 2013 16:19