Irinotecan Pathway (Pan troglodytes)

From WikiPathways

Jump to: navigation, search
1, 2DiarrheaModel human liver cell showing blood, bile and intestinal compartments, indicating tissueinvolvment of genes in the irinotecan pathway.IntestineLiver CellNeutropeniaABCC1CES1UGT1A10CES1CYP3A4SN-38SN-38GCYP3A5ABCC2UGT1A6SN-38CYP3A4M4UGT1A6BCHEUGT1A1ABCC2UGT1A9APCABCC1ABCC1SN-38IrinotecanCES1ABCG2CES1CES2CES2IrinotecanCES2CES2CYP3A5NPC1CYP3A4SN-38GIrinotecanUGT1A1ABCC2


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 65% conversion rate.

Quality Tags

Ontology Terms

 

Bibliography

  1. 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
  2. Desai AA, Innocenti F, Ratain MJ; ''UGT pharmacogenomics: implications for cancer risk and cancer therapeutics.''; Pharmacogenetics, 2003 PubMed Europe PMC

History

View all...
CompareRevisionActionTimeUserComment
93193view15:16, 2 August 2017DeSlChanged several gene nodes to metabolite nodes, added IDs for them
69250view18:36, 8 July 2013MaintBotUpdated to 2013 gpml schema
67412view10:58, 26 June 2013DdiglesOntology Term : 'irinotecan drug pathway' added !
57481view21:56, 28 January 2013KhanspersChanged identifier for irinotecan
57180view16:24, 23 January 2013EgonwUsed "PubChem-compound"
41557view01:59, 2 March 2011MaintBotRemoved redundant pathway information and comments
35501view13:12, 12 February 2010ThomasModified description
35500view13:11, 12 February 2010Thomasadded literature, removed genmapp comment
34288view22:00, 9 December 2009MaintBotAutomatic update of empty xrefs
33610view09:59, 1 December 2009MaintBotRemoved group label
31624view22:20, 13 August 2009MaintBotFixed text labels
30530view21:53, 29 July 2009MaintBotNew pathway

External references

DataNodes

View all...
NameTypeDatabase referenceComment
ABCC1GeneProduct453952 (Entrez Gene)
ABCC2GeneProduct450670 (Entrez Gene)
ABCG2GeneProduct471251 (Entrez Gene)
APCGeneProduct461999 (Entrez Gene)
BCHEGeneProduct460830 (Entrez Gene)
CES1GeneProduct747009 (Entrez Gene)
CES2GeneProduct740768 (Entrez Gene)
CYP3A4GeneProduct463582 (Entrez Gene)
CYP3A5GeneProduct737374 (Entrez Gene)
IrinotecanMetabolite60838 (PubChem-compound)
M4Metabolitemolecular weight, 558
NPC1GeneProduct4864 (Entrez Gene)
SN-38MetaboliteCHEBI:8988 (ChEBI)
SN-38GMetaboliteCHEBI:8990 (ChEBI)
UGT1A10GeneProduct54575 (Entrez Gene)
UGT1A1GeneProduct449596 (Entrez Gene)
UGT1A6GeneProduct739942 (Entrez Gene)
UGT1A9GeneProduct741990 (Entrez Gene)

Annotated Interactions

No annotated interactions
Personal tools