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Identification
Name Irinotecan
Accession Number DB00762 (APRD00579)
Type small molecule
Groups approved
Description

Irinotecan is an antineoplastic enzyme inhibitor primarily used in the treatment of colorectal cancer. It is a derivative of camptothecin that inhibits the action of topoisomerase I. Irinotecan prevents religation of the DNA strand by binding to topoisomerase I-DNA complex, and causes double-strand DNA breakage and cell death.
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
Irinotecan Hcl
Irinotecan Hydrochloride
Irinotecan Hydrochloride Trihydrate
Irinotecanum [INN-Latin]
Salts Not Available
Brand names
Name Company
Camptosar
CP0
IRINOTECAN, CPT-11
Brand mixtures Not Available
Categories
  • Antineoplastic Agents
  • Radiation-Sensitizing Agents
  • Parasympathomimetics
  • Enzyme Inhibitors
  • Prodrugs
  • Antineoplastic Agents, Phytogenic
CAS number 100286-90-6
Weight Average: 586.678
Monoisotopic: 586.279134968
Chemical Formula C33H38N4O6
InChI Key InChIKey=UWKQSNNFCGGAFS-XIFFEERXSA-N
InChI
InChI=1S/C33H38N4O6/c1-3-22-23-16-21(43-32(40)36-14-10-20(11-15-36)35-12-6-5-7-13-35)8-9-27(23)34-29-24(22)18-37-28(29)17-26-25(30(37)38)19-42-31(39)33(26,41)4-2/h8-9,16-17,20,41H,3-7,10-15,18-19H2,1-2H3/t33-/m0/s1
Plain Text
IUPAC Name
(19S)-10,19-diethyl-19-hydroxy-14,18-dioxo-17-oxa-3,13-diazapentacyclo[11.8.0.0^{2,11}.0^{4,9}.0^{15,20}]henicosa-1(21),2(11),3,5,7,9,15(20)-heptaen-7-yl 4-(piperidin-1-yl)piperidine-1-carboxylate
SMILES
CCC1=C2CN3C(=CC4=C(COC(=O)[C@]4(O)CC)C3=O)C2=NC2=C1C=C(OC(=O)N1CCC(CC1)N1CCCCC1)C=C2
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Camptothecins
Substructures
  • Carboxylic Acids and Derivatives
  • Hydroxy Compounds
  • Pyrans
  • Acetates
  • Carbamates and Derivatives
  • Phenols and Derivatives
  • Lactones
  • Pyridines and Derivatives
  • Ethers
  • Benzene and Derivatives
  • Bipyridines
  • Hydroxyquinolines
  • Camptothecins
  • Aliphatic and Aryl Amines
  • Alcohols and Polyols
  • Pyridines
  • Heterocyclic compounds
  • Aromatic compounds
  • Anisoles
  • (Iso)quinolines and Derivatives
  • Imines
  • Phenyl Esters
  • Piperidines
Pharmacology
Indication For the treatment of metastatic colorectal cancer (first-line therapy when administered with 5-fluorouracil and leucovorin). Also used in combination with cisplatin for the treatment of extensive small cell lung cancer. Irinotecan is currently under investigation for the treatment of metastatic or recurrent cervical cancer.
Pharmacodynamics Irinotecan is an antineoplastic enzyme inhibitor primarily used in the treatment of colorectal cancer. Irinotecan is a semisynthetic derivative of camptothecin. Camptothecins interact specifically with topoisomerase I, an enzyme in the cell nucleus that regulates DNA topology and facilitates nuclear processes such as DNA replication, recombination, and repair. During these processes, topoisomerase I relieves torsional strain in DNA by inducing reversible single-strand breaks, allowing single DNA strands to pass through the break. The 3'-DNA terminus of the broken DNA strands bind covalently with the topoisomerase enzyme to form a catalytic intermediate called a cleavable complex. After the DNA is sufficiently relaxed and the strand passage reaction is complete, DNA topoisomerase reattaches the broken DNA strands to form the chemically unaltered topoisomers that allow transcription to proceed. Irinotecan and its active metabolite SN-38 bind to the topoisomerase I-DNA complex and prevent religation of these single-strand breaks. Current research suggests that the cytotoxicity of irinotecan is due to double-strand DNA damage produced during DNA synthesis when replication enzymes interact with the ternary complex formed by topoisomerase I, DNA, and either Irinotecan or SN-38. Mammalian cells cannot efficiently repair these double-strand breaks. The precise contribution of SN-38 to the activity of irinotecan in humans is not known. Irinotecan is cell cycle phase-specific (S-phase).
Mechanism of action Irinotecan inhibits the action of topoisomerase I. Irinotecan prevents religation of the DNA strand by binding to topoisomerase I-DNA complex. The formation of this ternary complex interferes with the moving replication fork, which induces replication arrest and lethal double-stranded breaks in DNA. As a result, DNA damage is not efficiently repaired and apoptosis (programmed cell death) occurs.
Absorption 100%
Volume of distribution Not Available
Protein binding 30%-68%
Metabolism
Hepatic
Route of elimination The cumulative biliary and urinary excretion of irinotecan and its metabolites (SN-38 and SN-38 glucuronide) over a period of 48 hours following administration of irinotecan in two patients ranged from approximately 25% (100 mg/m2) to 50% (300 mg/m2).
Half life 6-12 hours
Clearance Not Available
Toxicity Gastrointestinal complications, such as nausea, vomiting, abdominal cramping, diarrhea, and infection.
Affected organisms
  • Humans and other mammals
Pathways
Pathway Name SMPDB ID
Smp00433 Irinotecan Pathway SMP00433
Pharmacoeconomics
Manufacturers
  • Pfizer inc
  • Accord healthcare inc
  • Actavis totowa llc
  • Akorn inc
  • App pharmaceuticals
  • Bedford laboratories
  • Dr reddys laboratories ltd
  • Ebewe pharma ges mbh nfg kg
  • Fresenius kabi oncology plc
  • Hospira inc
  • Pharmaforce inc
  • Pliva lachema as
  • Sandoz inc
  • Sun pharma global inc
  • Teva parenteral medicines inc
  • Watson laboratories inc
Packagers
Dosage forms
Form Route Strength
Solution Intravenous
Prices
Unit description Cost Unit
Irinotecan hcl 40 mg/2 ml inj 138.07 USD ml
Camptosar 20 mg/ml vial 36.0 USD ml
Irinotecan hcl 40 mg/2 ml vial 22.2 USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Country Patent Number Approved Expires (estimated)
United States 6794370 2000-11-01 2020-11-01
United States 6403569 2000-04-28 2020-04-28
Canada 2202531 2005-05-03 2015-10-11
Canada 2294031 2005-01-18 2018-07-27
Properties
State solid
Experimental Properties
Property Value Source
melting point 222-223 °C Not Available
water solubility Soluble Not Available
logP 3.2 Not Available
Predicted Properties
Property Value Source
water solubility 1.07e-01 g/l ALOGPS
logP 3.94 ALOGPS
logP 2.78 ChemAxon
logS -3.7 ALOGPS
pKa (strongest acidic) 11.71 ChemAxon
pKa (strongest basic) 9.47 ChemAxon
physiological charge 1 ChemAxon
hydrogen acceptor count 6 ChemAxon
hydrogen donor count 1 ChemAxon
polar surface area 112.51 ChemAxon
rotatable bond count 5 ChemAxon
refractivity 161.33 ChemAxon
polarizability 65.27 ChemAxon
References
Synthesis Reference Not Available
General Reference
  1. Innocenti F, Undevia SD, Iyer L, Chen PX, Das S, Kocherginsky M, Karrison T, Janisch L, Ramirez J, Rudin CM, Vokes EE, Ratain MJ: Genetic variants in the UDP-glucuronosyltransferase 1A1 gene predict the risk of severe neutropenia of irinotecan. J Clin Oncol. 2004 Apr 15;22(8):1382-8. Epub 2004 Mar 8. Pubmed
  2. O’Dwyer PJ, Catalano RB: Uridine diphosphate glucuronosyltransferase (UGT) 1A1 and irinotecan: practical pharmacogenomics arrives in cancer therapy. J Clin Oncol. 2006 Oct 1;24(28):4534-8. Pubmed
  3. Ramesh M, Ahlawat P, Srinivas NR: Irinotecan and its active metabolite, SN-38: review of bioanalytical methods and recent update from clinical pharmacology perspectives. Biomed Chromatogr. 2010 Jan;24(1):104-23. Pubmed
  4. Chabot GG: Clinical pharmacokinetics of irinotecan. Clin Pharmacokinet. 1997 Oct;33(4):245-59. Pubmed
External Links
Resource Link
KEGG Drug D08086 Link_out
PubChem Compound 60838 Link_out
PubChem Substance 46505871 Link_out
ChemSpider 54825 Link_out
Therapeutic Targets Database DAP001339 Link_out
PharmGKB PA450085 Link_out
Drug Product Database 2231622 Link_out
RxList http://www.rxlist.com/cgi/generic2/irinot.htm Link_out
Drugs.com http://www.drugs.com/cdi/irinotecan.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Irinotecan Link_out
ATC Codes
  • L01XX19
AHFS Codes
  • 10:00.00
PDB Entries Not Available
FDA label show (132 KB)
MSDS show (36.3 KB)
Interactions
Drug Interactions
Drug Interaction
Aprepitant Aprepitant may change levels of the chemotherapy agent, irinotecan.
Atazanavir Increases levels/effect of irinotecan
Fosphenytoin The hydantoin decreases the effect of irinotecan
Ketoconazole Ketoconazole increases the effect and toxicity of irinotecan
Pazopanib Irinotecan is an uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) substrate and serum concentrations may increase if administered concurrently with pazopanib, an UGT1A1 inhibitor.
Phenytoin The hydantoin decreases the effect of irinotecan
Regorafenib Regorafenib may increase levels of irinotecan, a UGT1A1 substrate.
Telithromycin Telithromycin may reduce clearance of Irinotecan. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Irinotecan if Telithromycin is initiated, discontinued or dose changed.
Thiotepa Thiotepa, a strong CYP2B6 inhibitor, may decrease the metabolism and clearance of Irinotecan, a CYP2B6 substrate. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of Irinotecan if Thiotepa 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 irinotecan by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of irinotecan if voriconazole is initiated, discontinued or dose changed.
Food Interactions Not Available
Targets

1. DNA topoisomerase 1

Pharmacological action: yes
Actions: inhibitor

The reaction catalyzed by topoisomerases leads to the conversion of one topological isomer of DNA to another

Organism class: human
UniProt ID: P11387 Link_out
Gene: TOP1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Yoshikawa M, Ikegami Y, Hayasaka S, Ishii K, Ito A, Sano K, Suzuki T, Togawa T, Yoshida H, Soda H, Oka M, Kohno S, Sawada S, Ishikawa T, Tanabe S: Novel camptothecin analogues that circumvent ABCG2-associated drug resistance in human tumor cells. Int J Cancer. 2004 Jul 20;110(6):921-7. Pubmed
  2. Yoshikawa M, Ikegami Y, Sano K, Yoshida H, Mitomo H, Sawada S, Ishikawa T: Transport of SN-38 by the wild type of human ABC transporter ABCG2 and its inhibition by quercetin, a natural flavonoid. J Exp Ther Oncol. 2004 Apr;4(1):25-35. Pubmed
  3. Yang X, Hu Z, Chan SY, Chan E, Goh BC, Duan W, Zhou S: Novel agents that potentially inhibit irinotecan-induced diarrhea. Curr Med Chem. 2005;12(11):1343-58. Pubmed
  4. Nakagawa H, Saito H, Ikegami Y, Aida-Hyugaji S, Sawada S, Ishikawa T: Molecular modeling of new camptothecin analogues to circumvent ABCG2-mediated drug resistance in cancer. Cancer Lett. 2006 Mar 8;234(1):81-9. Epub 2005 Nov 23. Pubmed
  5. Ishikawa T, Ikegami Y, Sano K, Nakagawa H, Sawada S: Transport mechanism-based drug molecular design: novel camptothecin analogues to circumvent ABCG2-associated drug resistance of human tumor cells. Curr Pharm Des. 2006;12(3):313-25. Pubmed
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
  7. Ramesh M, Ahlawat P, Srinivas NR: Irinotecan and its active metabolite, SN-38: review of bioanalytical methods and recent update from clinical pharmacology perspectives. Biomed Chromatogr. 2010 Jan;24(1):104-23. Pubmed
  8. Chabot GG: Clinical pharmacokinetics of irinotecan. Clin Pharmacokinet. 1997 Oct;33(4):245-59. Pubmed

2. DNA topoisomerase I, mitochondrial

Pharmacological action: yes
Actions: inhibitor

Relieves DNA strain that arise during duplication of mitochondrial DNA

Organism class: human
UniProt ID: Q969P6 Link_out
Gene: TOP1MT 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. Yoshikawa M, Ikegami Y, Hayasaka S, Ishii K, Ito A, Sano K, Suzuki T, Togawa T, Yoshida H, Soda H, Oka M, Kohno S, Sawada S, Ishikawa T, Tanabe S: Novel camptothecin analogues that circumvent ABCG2-associated drug resistance in human tumor cells. Int J Cancer. 2004 Jul 20;110(6):921-7. Pubmed
  4. Yoshikawa M, Ikegami Y, Sano K, Yoshida H, Mitomo H, Sawada S, Ishikawa T: Transport of SN-38 by the wild type of human ABC transporter ABCG2 and its inhibition by quercetin, a natural flavonoid. J Exp Ther Oncol. 2004 Apr;4(1):25-35. Pubmed
  5. Yang X, Hu Z, Chan SY, Chan E, Goh BC, Duan W, Zhou S: Novel agents that potentially inhibit irinotecan-induced diarrhea. Curr Med Chem. 2005;12(11):1343-58. Pubmed
  6. Nakagawa H, Saito H, Ikegami Y, Aida-Hyugaji S, Sawada S, Ishikawa T: Molecular modeling of new camptothecin analogues to circumvent ABCG2-mediated drug resistance in cancer. Cancer Lett. 2006 Mar 8;234(1):81-9. Epub 2005 Nov 23. Pubmed
  7. Ishikawa T, Ikegami Y, Sano K, Nakagawa H, Sawada S: Transport mechanism-based drug molecular design: novel camptothecin analogues to circumvent ABCG2-associated drug resistance of human tumor cells. Curr Pharm Des. 2006;12(3):313-25. Pubmed
  8. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
  9. Ramesh M, Ahlawat P, Srinivas NR: Irinotecan and its active metabolite, SN-38: review of bioanalytical methods and recent update from clinical pharmacology perspectives. Biomed Chromatogr. 2010 Jan;24(1):104-23. Pubmed
  10. Chabot GG: Clinical pharmacokinetics of irinotecan. Clin Pharmacokinet. 1997 Oct;33(4):245-59. Pubmed
Enzymes

1. 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. Ramesh M, Ahlawat P, Srinivas NR: Irinotecan and its active metabolite, SN-38: review of bioanalytical methods and recent update from clinical pharmacology perspectives. Biomed Chromatogr. 2010 Jan;24(1):104-23. Pubmed
  2. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  3. 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
  4. Kuhn JG: Pharmacology of irinotecan. Oncology (Williston Park). 1998 Aug;12(8 Suppl 6):39-42. Pubmed

2. 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

3. Liver carboxylesterase 1

Actions: substrate

Involved in the detoxification of xenobiotics and in the activation of ester and amide prodrugs. Hydrolyzes aromatic and aliphatic esters, but has no catalytic activity toward amides or a fatty acyl CoA ester

UniProt ID: P23141 Link_out
Gene: CES1
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Chabot GG: Clinical pharmacokinetics of irinotecan. Clin Pharmacokinet. 1997 Oct;33(4):245-59. Pubmed
  2. Ramesh M, Ahlawat P, Srinivas NR: Irinotecan and its active metabolite, SN-38: review of bioanalytical methods and recent update from clinical pharmacology perspectives. Biomed Chromatogr. 2010 Jan;24(1):104-23. Pubmed
  3. Kuhn JG: Pharmacology of irinotecan. Oncology (Williston Park). 1998 Aug;12(8 Suppl 6):39-42. Pubmed

4. 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.

5. Cytochrome P450 2B6

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: P20813 Link_out
Gene: CYP2B6 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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. Pubmed

6. UDP-glucuronosyltransferase 1-1

Actions: substrate

UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform glucuronidates bilirubin IX- alpha to form both the IX-alpha-C8 and IX-alpha-C12 monoconjugates and diconjugate

UniProt ID: P22309 Link_out
Gene: UGT1A1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Kuhn JG: Pharmacology of irinotecan. Oncology (Williston Park). 1998 Aug;12(8 Suppl 6):39-42. Pubmed

7. UDP-glucuronosyltransferase 1-9

Actions: substrate

UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform has specificity for phenols

UniProt ID: O60656 Link_out
Gene: UGT1A9 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Chabot GG: Clinical pharmacokinetics of irinotecan. Clin Pharmacokinet. 1997 Oct;33(4):245-59. Pubmed
Transporters

1. 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

2. Solute carrier organic anion transporter family member 1B1

Actions: inhibitor

Mediates the Na(+)-independent transport of organic anions such as pravastatin, taurocholate, methotrexate, dehydroepiandrosterone sulfate, 17-beta-glucuronosyl estradiol, estrone sulfate, prostaglandin E2, thromboxane B2, leukotriene C3, leukotriene E4, thyroxine and triiodothyronine. May play an important role in the clearance of bile acids and organic anions from the liver

UniProt ID: Q9Y6L6 Link_out
Gene: SLCO1B1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Nozawa T, Minami H, Sugiura S, Tsuji A, Tamai I: Role of organic anion transporter OATP1B1 (OATP-C) in hepatic uptake of irinotecan and its active metabolite, 7-ethyl-10-hydroxycamptothecin: in vitro evidence and effect of single nucleotide polymorphisms. Drug Metab Dispos. 2005 Mar;33(3):434-9. Epub 2004 Dec 17. Pubmed

3. Multidrug resistance-associated protein 1

Actions: substrate

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. Chen ZS, Furukawa T, Sumizawa T, Ono K, Ueda K, Seto K, Akiyama SI: ATP-Dependent efflux of CPT-11 and SN-38 by the multidrug resistance protein (MRP) and its inhibition by PAK-104P. Mol Pharmacol. 1999 May;55(5):921-8. Pubmed

4. 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. Wang X, Furukawa T, Nitanda T, Okamoto M, Sugimoto Y, Akiyama S, Baba M: Breast cancer resistance protein (BCRP/ABCG2) induces cellular resistance to HIV-1 nucleoside reverse transcriptase inhibitors. Mol Pharmacol. 2003 Jan;63(1):65-72. Pubmed
  2. Maliepaard M, van Gastelen MA, Tohgo A, Hausheer FH, van Waardenburg RC, de Jong LA, Pluim D, Beijnen JH, Schellens JH: Circumvention of breast cancer resistance protein (BCRP)-mediated resistance to camptothecins in vitro using non-substrate drugs or the BCRP inhibitor GF120918. Clin Cancer Res. 2001 Apr;7(4):935-41. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on February 08, 2013 16:19