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UDP glucuronosyltransferase 1 family, polypeptide A9

This gene encodes a UDP-glucuronosyltransferase, an enzyme of the glucuronidation pathway that transforms small lipophilic molecules, such as steroids, bilirubin, hormones, and drugs, into water-soluble, excretable metabolites. This gene is part of a complex locus that encodes several UDP-glucuronosyltransferases. The locus includes thirteen unique alternate first exons followed by four common exons. Four of the alternate first exons are considered pseudogenes. Each of the remaining nine 5' exons may be spliced to the four common exons, resulting in nine proteins with different N-termini and identical C-termini. Each first exon encodes the substrate binding site, and is regulated by its own promoter. The enzyme encoded by this gene is active on phenols. [provided by RefSeq, Jul 2008] (from NCBI)
Top mentioned proteins: UDP-glucuronosyltransferase, UGT, Glucuronosyltransferase, UGT1A1, UGT2B7
Papers on UGT1A9
New insights into the risk of phthalates: Inhibition of UDP-glucuronosyltransferases.
Fang et al., Jinzhou, China. In Chemosphere, Feb 2016
100 µM of DNOP inhibited the activities of UGT1A3, UGT1A9, and UGT2B7 by 41.8% (p < 0.01), 45.6% (p < 0.01), and 48.8% (p < 0.01), respectively.
Effect of dapagliflozin on colon cancer cell [Rapid Communication].
Yamada et al., Japan. In Endocr J, Jan 2016
Dapagliflozin is metabolized by UGT1A9 (UDP Glucuronosyltransferase 1 family, Polypeptidase A9), suppressing its SGLT2 inhibitor activity.
Metabolism and pharmacokinetics of 8-hydroxypiperidinylmethyl-baicalein (BA-j) as a novel selective CDK1 inhibitor in monkey.
Zheng et al., Dalian, China. In Fitoterapia, Dec 2015
The major metabolic pathways of BA-j, by capturing oxygen free radicals ((.)O2(-)) and releasing peroxides (H2O2), are degraded into active intermediate metabolite dihydroflavonol, then into main metabolite M179 by Shiff reaction, second metabolite M264 by sulfation, trace amount of metabolite M559 by glucuronidation UGT1A9, and without metabolism by CYP3A4.
Stereospecific Metabolism of the Tobacco-Specific Nitrosamine, NNAL.
Lazarus et al., Spokane, United States. In Chem Res Toxicol, Dec 2015
Comparison of NNAL glucuronides (NNAL-Glucs) formed in reactions of UGT2B7-, UGT2B17-, UGT1A9-, and UGT2B10-overexpressing cell microsomes with pure NNAL enantiomers showed large differences in kinetics for (S)- versus (R)-NNAL, indicating varying levels of enantiomeric preference for each enzyme.
Curcumin Affects Phase II Disposition of Resveratrol Through Inhibiting Efflux Transporters MRP2 and BCRP.
Hu et al., Houston, United States. In Pharm Res, Nov 2015
Human UGT1A9-overexpressing HeLa cells and human MRP2-overexpressing MDCK II-UGT1A1 cells were used as in vitro tools to further determine the impact of curcumin as a transporter inhibitor on resveratrol metabolites.
Pharmacogenetic biomarkers predictive of the pharmacokinetics and pharmacodynamics of immunosuppressive drugs.
Haufroid et al., Brussels, Belgium. In Ther Drug Monit, Nov 2015
However, despite some evidence of clear associations between polymorphisms in genes encoding metabolizing enzymes (CYP3A4/3A5, UGT1A9) or drug transporters (ABCB1, ABCC2, SLCO1B1) and pharmacokinetics of several immunosuppressive drugs, pre-emptive genotyping and selection of the optimal starting dose based on the genetic background of the patient is still rarely performed in clinical practice.
Drug-Drug Interaction Potentials of Tyrosine Kinase Inhibitors via Inhibition of UDP-Glucuronosyltransferases.
Jeong et al., Chicago, United States. In Sci Rep, 2014
The TKIs also exerted intermediate inhibition against several UGTs (i.e., UGT1A7 by lapatinib; UGT1A1 by imatinib; UGT1A4, 1A7 and 1A9 by axitinib; and UGT1A9 by vandetanib).
Resveratrol as a Bioenhancer to Improve Anti-Inflammatory Activities of Apigenin.
Choi et al., South Korea. In Nutrients, 2014
When the action of resveratrol on the main apigenin metabolizing enzymes, UDP-glucuronosyltransferases (UGTs), was investigated, resveratrol mainly inhibited the formation of apigenin glucuronides by UGT1A9 in a non-competitive manner with a Ki value of 7.782 μM.
Pharmacology and toxicology of mycophenolate in organ transplant recipients: an update.
Tett et al., Brisbane, Australia. In Arch Toxicol, 2014
Genetic variants within genes involved in MPA metabolism (UGT1A9, UGT1A8, UGT2B7), cellular transportation (SLCOB1, SLCO1B3, ABCC2) and targets (IMPDH) have been reported to effect MPA pharmacokinetics and/or response in some studies; however, larger studies across different ethnic groups that take into account genetic linkage and drug interactions that can alter a patient's phenotype are needed before any clinical recommendations based on patient genotype can be formulated.
Renal drug metabolism in humans: the potential for drug-endobiotic interactions involving cytochrome P450 (CYP) and UDP-glucuronosyltransferase (UGT).
Miners et al., Adelaide, Australia. In Br J Clin Pharmacol, 2013
NSAIDs) of the intrarenal activity of UGT1A9 and UGT2B7 has the potential to perturb the metabolism of renal mediators including aldosterone, prostaglandins and 20-hydroxyeicosatetraenoic acid, thus disrupting renal homeostasis.
The impact of genetic factors on response to anaesthetics.
Slomski et al., Poznań, Poland. In Adv Med Sci, 2012
Among genes associated with metabolism of the most commonly applied anaesthetics such as propofol and sevoflurane, the following ones can be mentioned: CYP2E1, CYP2B6, CYP2C9, GSTP1, UGT1A9, SULT1A1 and NQO1.
Functional impact and prevalence of polymorphisms involved in the hepatic glucuronidation of valproic acid.
Markoula et al., Ioánnina, Greece. In Pharmacogenomics, 2012
UGTs metabolizing valproic acid in the liver are UGT1A3, UGT1A4, UGT1A6, UGT1A9 and UGT2B7, with UGT1A6 and UGT2B7 being the most prominent.
Accurate prediction of glucuronidation of structurally diverse phenolics by human UGT1A9 using combined experimental and in silico approaches.
Hu et al., Houston, United States. In Pharm Res, 2012
Report molecular models that can predict phenol substrate selectivity and in vitro clearance of UGT1A9.
Sorafenib is an inhibitor of UGT1A1 but is metabolized by UGT1A9: implications of genetic variants on pharmacokinetics and hyperbilirubinemia.
Figg et al., Bethesda, United States. In Clin Cancer Res, 2012
Study indicates that genotype status of UGT1A1, UGT1A9, and ABCC2 and serum bilirubin concentration increases reflect abnormally high AUC in patients treated with sorafenib.
Metabolism and pharmacokinetics of morinidazole in humans: identification of diastereoisomeric morpholine N+-glucuronides catalyzed by UDP glucuronosyltransferase 1A9.
Chen et al., Shanghai, China. In Drug Metab Dispos, 2012
Investigation of morinidazole glucuronidation using human liver microsomes (HLMs) and 12 recombinant UDP glucuronosyltransferases (UGTs) indicated that this biotransformation was mainly catalyzed by UGT1A9.
Identification of UDP-glucuronosyltransferases responsible for the glucuronidation of darexaban, an oral factor Xa inhibitor, in human liver and intestine.
Usui et al., Ōsaka, Japan. In Drug Metab Dispos, 2012
Data suggest that darexaban glucuronidation in liver microsomes is mainly catalyzed by UGT1A9; studies include kinetics of recombinant UGT proteins, liver microsomes, and jejunal microsomes (and UGT isoform-specific inhibitors/substrates).
Association of UDP-glucuronosyltransferase 1A9 (UGT1A9) gene polymorphism with kidney allograft function.
Malejczyk et al., Warsaw, Poland. In Ann Transplant, 2011
transplanted kidney function may be affected in patients carrying UGT1A9 98C allele and receiving mycophenolate mophetil
Mycophenolate, clinical pharmacokinetics, formulations, and methods for assessing drug exposure.
Cattaneo et al., Brisbane, Australia. In Transplant Rev (orlando), 2011
Assessment of UGT1A9 single nucleotide polymorphisms (-275TNA, -2152CNT, -440CNT, -331TNC) should be considered before transplantation to assist in dosing decisions to achieve optimal MPA exposure immediately after transplant.
Predictive role of the UGT1A1, UGT1A7, and UGT1A9 genetic variants and their haplotypes on the outcome of metastatic colorectal cancer patients treated with fluorouracil, leucovorin, and irinotecan.
Toffoli et al., Italy. In J Clin Oncol, 2009
UGT1A variants additional to UGT1A1*28 might improve the prediction of the outcome of colorectal cancer patients treated with FOLFIRI.
Comprehensive analysis of UGT1A polymorphisms predictive for pharmacokinetics and treatment outcome in patients with non-small-cell lung cancer treated with irinotecan and cisplatin.
Lee et al., South Korea. In J Clin Oncol, 2006
PURPOSE: To determine whether uridine diphosphate-glucuronosyltransferase 1A1, UGT1A7, and UGT1A9 polymorphisms affect the pharmacokinetics (PK) of irinotecan and treatment outcome of Korean patients with advanced non-small-cell lung cancer (NSCLC).
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