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GENE - CHEMICAL INTERACTIONS REPORT

RGD ID: 11476
Species: Mus musculus
RGD Object: Gene
Symbol: Ugt1a1
Name: UDP glucuronosyltransferase 1 family, polypeptide A1
Acc ID: CHEBI:80630
Term: irinotecan
Definition: A member of the class of pyranoindolizinoquinolines that is the carbamate ester obtained by formal condensation of the carboxy group of [1,4'-bipiperidine]-1'-carboxylic acid with the phenolic hydroxy group of (4S)-4,11-diethyl-4,9-dihydroxy-1H-pyrano[3',4':6,7]indolizino[1,2- hydrochloride]quinoline-3,14-dione. Used (in the form of its hydrochloride salt trihydrate) in combination with fluorouracil and leucovorin, for the treatment of patients with metastatic adenocarcinoma of the pancreas after disease progression following gemcitabine-based therapy. It is converted via hydrolysis of the carbamate linkage to its active metabolite, SN-38, which is ~1000 times more active.
Chemical ID: MESH:D000077146
Note: Use of the qualifier "multiple interactions" designates that the annotated interaction is comprised of a complex set of reactions and/or regulatory events, possibly involving additional chemicals and/or gene products.
Object SymbolQualifierEvidenceWithReferenceSourceNotesOriginal Reference(s)
Ugt1a1decreases activityEXP 6480464CTDIrinotecan results in decreased activity of UGT1A1 proteinPMID:35728726
Ugt1a1decreases expressionEXP 6480464CTDIrinotecan results in decreased expression of UGT1A1 mRNAPMID:35728726
Ugt1a1multiple interactionsEXP 6480464CTDMYD88 protein affects the reaction [Irinotecan results in decreased expression of UGT1A1 mRNA]; TLR2 protein affects the reaction [Irinotecan results in decreased expression of UGT1A1 mRNA]; TLR4 protein affects the reaction [Irinotecan results in decreased expression of UGT1A1 mRNA]PMID:35728726
Ugt1a1affects glucuronidationISOUGT1A1 (Homo sapiens)6480464CTDUGT1A1 protein mutant form affects the glucuronidation of IrinotecanPMID:35930428
Ugt1a1affects metabolic processingISOUGT1A1 (Homo sapiens)6480464CTDUGT1A1 protein affects the metabolism of IrinotecanPMID:15523087
Ugt1a1affects response to substanceISOUGT1A1 (Homo sapiens)6480464CTDUGT1A1 gene polymorphism affects the susceptibility to Irinotecan; UGT1A1 promoter polymorphism affects the susceptibility to Irinotecan; UGT1A1 protein affects the susceptibility to IrinotecanPMID:15517893 PMID:15858133 PMID:18300238 PMID:18478930
Ugt1a1decreases glucuronidationISOUGT1A1 (Homo sapiens)6480464CTDUGT1A1 gene mutant form results in decreased glucuronidation of Irinotecan; UGT1A1 protein polymorphism results in decreased glucuronidation of IrinotecanPMID:12960109 PMID:17898154
Ugt1a1increases glucuronidationISOUGT1A1 (Homo sapiens)6480464CTDUGT1A1 protein results in increased glucuronidation of IrinotecanPMID:15655543 PMID:15716465 PMID:15833930 PMID:17898154 PMID:35930428
Ugt1a1increases glucuronidationISOUgt1a1 (Rattus norvegicus)6480464CTDUGT1A1 protein results in increased glucuronidation of IrinotecanPMID:15833930
Ugt1a1increases metabolic processingISOUGT1A1 (Homo sapiens)6480464CTDUGT1A1 protein results in increased metabolism of IrinotecanPMID:23401472
Ugt1a1multiple interactionsISOUGT1A1 (Homo sapiens)6480464CTD[Ketoconazole results in decreased activity of UGT1A1 protein] which results in decreased metabolism of Irinotecan; [UGT1A1 protein mutant form affects the glucuronidation of Irinotecan] which results in decreased abundance of 7-ethyl-10-hydroxycamptothecin beta-glucuronide; [UGT1A1 protein results in increased glucuronidation of Irinotecan] which results in increased abundance of 7-ethyl-10-hydroxycamptothecin beta-glucuronide; UGT1A1 gene polymorphism affects the susceptibility to [Fluorouracil co-treated with Irinotecan]; UGT1A1 protein results in increased glucuronidation of and results in decreased activity of IrinotecanPMID:15517893 PMID:18797458 PMID:22447115 PMID:35930428
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