ArticleCancer chemotherapy and pharmacology2019
Lack of UGT polymorphism association with idasanutlin pharmacokinetics in solid tumor patients.
Article in Cancer chemotherapy and pharmacology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
2 citing papers in PubMed, 2 citations in OpenAlex.
- Insight into the structure, oligomerization, and the role in drug resistance of human UDP-glucuronosyltransferases.Archives of toxicology · 2025Review
- The role of E3 ubiquitin ligase HECTD3 in cancer and beyond.Cellular and molecular life sciences : CMLS · 2020Review
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeIdasanutlin is a selective small-molecule MDM2 antagonist. It activates the tumor suppressor TP53 and is in phase 3 clinical trial for acute myeloid leukemia. Nonclinical studies have shown that glucuronidation is the major metabolizing mechanism for idasanutlin and UGT1A3 is the major metabolizing enzyme. There are reported examples of UGT polymorphisms associated with drug metabolism or response. Thus, the aim of this analysis is to investigate if UGT polymorphism is associated with idasanutlin pharmacokinetics.
methodIdasanutlin clearance was derived and normalized from two phase I studies. Its clearance level was compared between patients with different genotypes at 44 non-monomorphic UGT SNPs. Several single-locus and multi-locus association analysis, including haplotype association analysis and pairwise SNP interaction (epistasis) analyses were performed to investigate if there is any association between UGT genotypes and idasanutlin clearance. RESULTS AND
conclusionA total of 69 patients who have both idasanutlin pharmacokinetic data and UGT genotyping data were analyzed for association. The major clearance enzyme for idasanutlin, UGT1A3, has no association with idasanutlin clearance. Further single-locus and multi-locus association analyses also suggest that no significant UGT polymorphism association with idasanutlin clearance can be detected with the current datasets. However, the possibility of association with rare allele(s) of UGT family genes cannot be excluded due to the limited sample size of the current phase I studies.
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