Loading Pathway...
Error: Pathway image not found.
Hide
Pathway Description
Irinotecan Action Pathway
Homo sapiens
Drug Action Pathway
Created: 2013-08-22
Last Updated: 2019-10-29
Irinotecan is a medication commonly sold as Camptosar, used to stop the growth of cancer cells, and to stop the spread of cancer cells in the human body. Specifically cancers of the rectum and of the colon. Commonly used in combination with chemotherapy. Irinotecan works through its active metabolite, SN-38, which inhibits the action of topoisomerase I. This enzyme is responsible for creating single-strand breaks in DNA during replication. These single-strands are reversible. SN-38 and Irinotecan binding to topoisomerase I-DNA complex results in the prevention of religation the DNA strand mentioned above, which creates double-strand DNA breakage. This breakage leads to cell death. Irinotecan is taken orally, but can also be injected.
References
Irinotecan Pathway References
Mathijssen RH, Loos WJ, Verweij J, Sparreboom A: Pharmacology of topoisomerase I inhibitors irinotecan (CPT-11) and topotecan. Curr Cancer Drug Targets. 2002 Jun;2(2):103-23.
Pubmed: 12188913
Rothenberg ML: Topoisomerase I inhibitors: review and update. Ann Oncol. 1997 Sep;8(9):837-55.
Pubmed: 9358934
Itoda M, Saito Y, Komamura K, Ueno K, Kamakura S, Ozawa S, Sawada J: Twelve novel single nucleotide polymorphisms in ABCB1/MDR1 among Japanese patients with ventricular tachycardia who were administered amiodarone. Drug Metab Pharmacokinet. 2002;17(6):566-71.
Pubmed: 15618713
Chen CJ, Chin JE, Ueda K, Clark DP, Pastan I, Gottesman MM, Roninson IB: Internal duplication and homology with bacterial transport proteins in the mdr1 (P-glycoprotein) gene from multidrug-resistant human cells. Cell. 1986 Nov 7;47(3):381-9. doi: 10.1016/0092-8674(86)90595-7.
Pubmed: 2876781
Chen CJ, Clark D, Ueda K, Pastan I, Gottesman MM, Roninson IB: Genomic organization of the human multidrug resistance (MDR1) gene and origin of P-glycoproteins. J Biol Chem. 1990 Jan 5;265(1):506-14.
Pubmed: 1967175
Abe T, Kakyo M, Tokui T, Nakagomi R, Nishio T, Nakai D, Nomura H, Unno M, Suzuki M, Naitoh T, Matsuno S, Yawo H: Identification of a novel gene family encoding human liver-specific organic anion transporter LST-1. J Biol Chem. 1999 Jun 11;274(24):17159-63. doi: 10.1074/jbc.274.24.17159.
Pubmed: 10358072
Hsiang B, Zhu Y, Wang Z, Wu Y, Sasseville V, Yang WP, Kirchgessner TG: A novel human hepatic organic anion transporting polypeptide (OATP2). Identification of a liver-specific human organic anion transporting polypeptide and identification of rat and human hydroxymethylglutaryl-CoA reductase inhibitor transporters. J Biol Chem. 1999 Dec 24;274(52):37161-8. doi: 10.1074/jbc.274.52.37161.
Pubmed: 10601278
Konig J, Cui Y, Nies AT, Keppler D: A novel human organic anion transporting polypeptide localized to the basolateral hepatocyte membrane. Am J Physiol Gastrointest Liver Physiol. 2000 Jan;278(1):G156-64. doi: 10.1152/ajpgi.2000.278.1.G156.
Pubmed: 10644574
Ito K, Olsen SL, Qiu W, Deeley RG, Cole SP: Mutation of a single conserved tryptophan in multidrug resistance protein 1 (MRP1/ABCC1) results in loss of drug resistance and selective loss of organic anion transport. J Biol Chem. 2001 May 11;276(19):15616-24. doi: 10.1074/jbc.M011246200. Epub 2001 Feb 21.
Pubmed: 11278867
Situ D, Haimeur A, Conseil G, Sparks KE, Zhang D, Deeley RG, Cole SP: Mutational analysis of ionizable residues proximal to the cytoplasmic interface of membrane spanning domain 3 of the multidrug resistance protein, MRP1 (ABCC1): glutamate 1204 is important for both the expression and catalytic activity of the transporter. J Biol Chem. 2004 Sep 10;279(37):38871-80. doi: 10.1074/jbc.M403832200. Epub 2004 Jun 18.
Pubmed: 15208328
Mitra P, Oskeritzian CA, Payne SG, Beaven MA, Milstien S, Spiegel S: Role of ABCC1 in export of sphingosine-1-phosphate from mast cells. Proc Natl Acad Sci U S A. 2006 Oct 31;103(44):16394-9. doi: 10.1073/pnas.0603734103. Epub 2006 Oct 18.
Pubmed: 17050692
Hsieh KP, Lin YY, Cheng CL, Lai ML, Lin MS, Siest JP, Huang JD: Novel mutations of CYP3A4 in Chinese. Drug Metab Dispos. 2001 Mar;29(3):268-73.
Pubmed: 11181494
Molowa DT, Schuetz EG, Wrighton SA, Watkins PB, Kremers P, Mendez-Picon G, Parker GA, Guzelian PS: Complete cDNA sequence of a cytochrome P-450 inducible by glucocorticoids in human liver. Proc Natl Acad Sci U S A. 1986 Jul;83(14):5311-5. doi: 10.1073/pnas.83.14.5311.
Pubmed: 3460094
Gonzalez FJ, Schmid BJ, Umeno M, Mcbride OW, Hardwick JP, Meyer UA, Gelboin HV, Idle JR: Human P450PCN1: sequence, chromosome localization, and direct evidence through cDNA expression that P450PCN1 is nifedipine oxidase. DNA. 1988 Mar;7(2):79-86. doi: 10.1089/dna.1988.7.79.
Pubmed: 3267210
Schuetz JD, Schuetz EG, Thottassery JV, Guzelian PS, Strom S, Sun D: Identification of a novel dexamethasone responsive enhancer in the human CYP3A5 gene and its activation in human and rat liver cells. Mol Pharmacol. 1996 Jan;49(1):63-72.
Pubmed: 8569713
Jounaidi Y, Guzelian PS, Maurel P, Vilarem MJ: Sequence of the 5'-flanking region of CYP3A5: comparative analysis with CYP3A4 and CYP3A7. Biochem Biophys Res Commun. 1994 Dec 30;205(3):1741-7. doi: 10.1006/bbrc.1994.2870.
Pubmed: 7811260
Aoyama T, Yamano S, Waxman DJ, Lapenson DP, Meyer UA, Fischer V, Tyndale R, Inaba T, Kalow W, Gelboin HV, et al.: Cytochrome P-450 hPCN3, a novel cytochrome P-450 IIIA gene product that is differentially expressed in adult human liver. cDNA and deduced amino acid sequence and distinct specificities of cDNA-expressed hPCN1 and hPCN3 for the metabolism of steroid hormones and cyclosporine. J Biol Chem. 1989 Jun 25;264(18):10388-95.
Pubmed: 2732228
Arlanov R, Porter A, Strand D, Brough R, Karpova D, Kerb R, Wojnowski L, Schwab M, Lang T: Functional characterization of protein variants of the human multidrug transporter ABCC2 by a novel targeted expression system in fibrosarcoma cells. Hum Mutat. 2012 Apr;33(4):750-62. doi: 10.1002/humu.22041. Epub 2012 Feb 28.
Pubmed: 22290738
Taniguchi K, Wada M, Kohno K, Nakamura T, Kawabe T, Kawakami M, Kagotani K, Okumura K, Akiyama S, Kuwano M: A human canalicular multispecific organic anion transporter (cMOAT) gene is overexpressed in cisplatin-resistant human cancer cell lines with decreased drug accumulation. Cancer Res. 1996 Sep 15;56(18):4124-9.
Pubmed: 8797578
Buchler M, Konig J, Brom M, Kartenbeck J, Spring H, Horie T, Keppler D: cDNA cloning of the hepatocyte canalicular isoform of the multidrug resistance protein, cMrp, reveals a novel conjugate export pump deficient in hyperbilirubinemic mutant rats. J Biol Chem. 1996 Jun 21;271(25):15091-8. doi: 10.1074/jbc.271.25.15091.
Pubmed: 8662992
Highlighted elements will appear in red.
Highlight Compounds
Highlight Proteins
Enter relative concentration values (without units). Elements will be highlighted in a color gradient where red = lowest concentration and green = highest concentration. For the best results, view the pathway in Black and White.
Visualize Compound Data
Visualize Protein Data
Settings