Irinotecan Pathway (Mus musculus)

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1, 2Model human liver cell showing blood, bile and intestinal compartments, indicating tissueinvolvment of genes in the irinotecan pathway.IntestineDiarrheaLiver CellNeutropeniaGm5744Gm5744BcheCes3ApcCes3CYP3A5Abcc1NPC1IrinotecanCes3SN-38Ugt1a6SN-38CYP3A4SN-38Abcc2Ces3CYP3A4SN-38GAbcc2Ugt1a10Ugt1a9Abcc1IrinotecanCYP3A4Gm5744CYP3A5Abcg2Abcc2Ugt1a1Ugt1a1Gm5744IrinotecanSN-38GUgt1a6Abcc1M4


Description

This pathway shows the biotransformation of the chemotherapy prodrug irinotecan to form the active metabolite SN-38, an inhibitor of DNA topoisomerase I. SN-38 is primarily metabolized to the inactive SN-38 glucuronide by UGT1A1, the isoform catalyzing bilirubin glucuronidation. Irinotecan is used in the treatment of metastatic colorectal cancer, small cell lung cancer and several other solid tumors. There is large interpatient variability in response to irinotecan, as well as severe side effects such as diarrhea and neutropenia, which might be explained in part by genetic variation in the metabolic enzymes and transporters depicted here. Well-known variants to effect this pathway are the promoter polymorphic repeat in UGT1A1 (UGT1A1*28) and the 1236C>T polymorphism in ABCB1. While UGT1A1*28 genotype has been associated with toxicity, further evidence is needed to describe the roles of ABCB1 variants in toxicity. Source: PharmGkb

Comments

HomologyConvert 
This pathway was inferred from Homo sapiens pathway WP229(r26589) with a 51% conversion rate.

Quality Tags

Ontology Terms

 

Bibliography

  1. Desai AA, Innocenti F, Ratain MJ; ''UGT pharmacogenomics: implications for cancer risk and cancer therapeutics.''; Pharmacogenetics, 2003 PubMed Europe PMC
  2. Mathijssen RH, Marsh S, Karlsson MO, Xie R, Baker SD, Verweij J, Sparreboom A, McLeod HL; ''Irinotecan pathway genotype analysis to predict pharmacokinetics.''; Clin Cancer Res, 2003 PubMed Europe PMC

History

View all...
CompareRevisionActionTimeUserComment
93210view18:51, 3 August 2017AlexanderPicoAdded ChEBI ID for APC metabolite
93198view15:52, 2 August 2017DeSlChanged several gene nodes to metabolite nodes, added IDs for them.
69144view18:17, 8 July 2013MaintBotUpdated to 2013 gpml schema
67411view10:58, 26 June 2013DdiglesOntology Term : 'irinotecan drug pathway' added !
48258view21:54, 17 May 2012KhanspersUpdating PubChem xrefs
41333view00:25, 2 March 2011MaintBotRemoved redundant pathway information and comments
35498view13:09, 12 February 2010ThomasModified description
35495view13:09, 12 February 2010Thomasadded literature, removed genmapp comment
32970view23:35, 28 September 2009MaintBotadded xrefs
32443view17:18, 15 August 2009MaintBotFixed text labels
32116view13:50, 14 August 2009MaintBotFixed group labels
31460view21:15, 13 August 2009MaintBotFixed text labels
30911view00:27, 30 July 2009MaintBotConverted from Homo sapiens
21680view11:32, 14 November 2008MaintBot[[Pathway:Mus musculus:Irinotecan pathway PharmGKB]] moved to [[Pathway:WP475]]: Moved to stable identifier
8226view13:46, 7 January 2008MaintBot[[Pathway:Mouse:Irinotecan pathway PharmGKB]] moved to [[Pathway:Mus musculus:Irinotecan pathway PharmGKB]]: Renaming species
7733view16:14, 18 December 2007MaintBotfixed category names
7480view12:42, 4 November 2007MaintBotAdded categories to GPML
6470view22:19, 22 May 2007169.230.77.174gpml file for [[Mouse:Irinotecan_pathway_PharmGKB]]

External references

DataNodes

View all...
NameTypeDatabase referenceComment
Abcc1GeneProduct17250 (Entrez Gene)
Abcc2GeneProduct12780 (Entrez Gene)
Abcg2GeneProduct26357 (Entrez Gene)
ApcMetaboliteCHEBI:80551 (ChEBI)
BcheGeneProduct12038 (Entrez Gene)
CYP3A4GeneProduct1576 (Entrez Gene)
CYP3A5GeneProduct1577 (Entrez Gene)
Ces3GeneProduct104158 (Entrez Gene)
Gm5744GeneProduct436059 (Entrez Gene)
IrinotecanMetabolite60838 (PubChem-compound)
M4Metabolitemolecular weight, 558
NPC1GeneProduct4864 (Entrez Gene)
SN-38MetaboliteCHEBI:8988 (ChEBI)
SN-38GMetaboliteCHEBI:8990 (ChEBI)
Ugt1a10GeneProduct394430 (Entrez Gene)
Ugt1a1GeneProduct394436 (Entrez Gene)
Ugt1a6GeneProduct94284 (Entrez Gene)
Ugt1a9GeneProduct394434 (Entrez Gene)

Annotated Interactions

No annotated interactions
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