Ask about this productRelated genes to: UGT1A6 antibody
- Gene:
- UGT1A6 NIH gene
- Name:
- UDP glucuronosyltransferase family 1 member A6
- Previous symbol:
- -
- Synonyms:
- HLUGP, GNT1, UGT1F
- Chromosome:
- 2q37.1
- Locus Type:
- complex locus constituent
- Date approved:
- 2000-06-22
- Date modifiied:
- 2016-10-05
Related products to: UGT1A6 antibody
Related articles to: UGT1A6 antibody
- PPAR agonists are promising therapeutic agents approved for managing dyslipidemia and insulin resistance, and emerging evidence suggests they may also affect thyroid hormone metabolism by modulating hepatic enzymes and transporters. We aimed to determine whether dual PPAR activation via saroglitazar modulates hepatic enzymes involved in thyroid hormone clearance, thereby bridging metabolic regulation with thyroid function. To investigate this possibility, female rats were dosed orally with saroglitazar (3, 10, or 30 mg/kg/day) for 28 days. Serum T4, T3, and TSH levels were measured using high-sensitivity immunoassays, and hepatic UGT isoforms and thyroid gene expression were assessed by qPCR. Saroglitazar modestly increased T4 and slightly reduced T3, while serum TSH remained stable, suggestive of a well-compensated HPT axis under the study conditions. Mechanistically, saroglitazar markedly induced hepatic UGT1A1 and UGT1A6, key enzymes in T4 glucuronidation and triggered compensatory upregulation of thyroid-specific genes (TSH, TPO, thyroglobulin, and the TSH receptor). Histological analysis revealed no adverse changes in the liver, thyroid, or pituitary glands. Overall, our findings indicate that saroglitazar modulates thyroid hormone homeostasis in rodents primarily via PPAR-mediated peripheral metabolism and intrinsic thyroidal compensation without central HPT disruption; these adaptive changes are rodent-specific due to the lack of thyroxine-binding globulin and unlikely to translate to humans. - Source: PubMed
Publication date: 2026/05/20
Jain Praveen KumarBhatt Laxit KPatel Ashvin KPatel SatyamPatani Kalpesh ZPatel Rajesh JDwivedi PankajKadam Shekhar BRanvir Ramchandra KPatel Hiren MChatterjee AbhijitGupta LaxmikantGiri PoonamPatel HarilalNyska AbrahamSundar RajeshJain Mukul R - Prediction of human intestinal metabolism within physiologically based pharmacokinetic models is now well established within drug development. Extrapolation of in vitro kinetic parameters accounts for differences in abundance between different in vitro systems and tissues. The existing data assume that the activity of CYP3A4 is consistent between the intestine and liver once adjusted for its tissue-specific expression level. However, the validity of this assumption for other enzymes and other tissues remains uncertain. In the current study, indicators of "activity per unit of enzyme," namely, turnover number (k) or specificity constant (k), were measured for 7 enzymes (CYP2C9, CYP2C19, CYP2D6, CYP3A4, UGT1A6, UGT2B7, and UGT2B17) in microsomes prepared from 4 paired (same donor) intestine and liver tissue samples. After excluding 1 donor with low intestinal activity, the intestinal k and k for the studied CYPs were within 2-fold of the liver values, with the exception of 1 donor with 4-fold lower CYP2D6 k in the intestine compared with the liver. Conversely, the UGT1A1 k and UGT2B7 k were 5-fold and 7-fold higher in intestinal microsomes compared with liver microsomes, respectively. Trends in interdonor variability in k were noted and require further evaluation in a larger set of donors. The current paradigm of extrapolation of hepatic metabolism data to predict in vivo first-pass metabolism in the intestine using tissue abundances appears to be valid for CYPs but should be approached with caution when predicting intestinal glucuronidation. SIGNIFICANCE STATEMENT: This study assessed whether hepatic metabolism data can predict intestinal metabolism in physiologically based pharmacokinetic models by comparing enzyme abundance and activity in matched liver and intestine microsomes from 4 donors. Seven key drug-metabolizing enzymes were quantified. While CYP-mediated intestinal metabolism could generally be predicted from liver data after adjusting for tissue abundance, caution is warranted for enzymes involved in intestinal glucuronidation, where assumptions of equivalent activity across tissues may not hold. - Source: PubMed
Publication date: 2025/12/29
Al-Majdoub Zubida MBarber JillRostami-Hodjegan AminGaletin AleksandraScotcher Daniel - Deferiprone, an iron chelator, causes variable adverse drug reactions (ADRs) in β-thalassemia patients, suggesting a role for pharmacogenetic factors. To address the lack of comprehensive pharmacogenetic data, this study investigated the association between four common variants - the primary enzyme metabolizing deferiprone - and the occurrence of specific ADRs, considering relevant clinical and personal characteristics. - Source: PubMed
Publication date: 2026/02/01
Najaflu MaliheNeufeld Ellis JMansourian MarjanGhanavat MajidSalehi Mansoor - Human hepatic carcinoma cell lines are widely used in vitro to study lipid and xenobiotic metabolism, as well as glucose regulation in both normal and diseased states. However, their validity is often questioned due to variability in protein expression compared to primary human hepatocytes (cHH). This study aimed to quantify protein abundance in various hepatic cell lines versus cHH and human liver tissue homogenate (HLT) using a data-independent acquisition-based total protein approach (DIA-TPA). We compared the global proteome from the whole cell homogenates of HepaRG, HepG2, and Huh7 cell lines with that of cHH and HLT. - Source: PubMed
Publication date: 2026/01/22
Saravanakumar AnithaJamwal RohitashBarlock Benjamin BBush XinAkhlaghi Fatemeh - Since pexidartinib was approved by the FDA for adult patients with tenosynovial giant cell tumor, increasing attention has been paid to its high frequency of adverse reactions. This study purposes to investigate the risk potential of pexidartinib-associated drug-drug interactions (DDIs) from the perspective of UDP-glucuronosyltransferases (UGTs) inhibition. Our results demonstrated that pexidartinib was a pan-inhibitor of UGTs, and it exhibited broad inhibition against 11 human recombinant UGT isoforms at clinically achievable concentrations, with IC values ranging from 0.97 to 20.02 μM. Further inhibition kinetic analysis showed that pexidartinib competitively inhibited UGT1A1, UGT1A6, UGT1A7, and UGT1A9, while exhibiting mixed inhibition toward UGT2B15. The values for them were calculated to be 4.27 ± 0.28, 1.72 ± 0.12, 1.67 ± 0.11, 0.65 ± 0.13, and 2.37 ± 0.45 μM, respectively. The results of - extrapolation (IVIVE) indicated that coadministration of pexidartinib at a clinically approved dose (400 mg twice daily) with the drugs primarily cleared by UGT1A1, UGT1A6, UGT1A7, UGT1A9, and UGT2B15 would result in a higher risk of DDI. In summary, our results provide useful information for the mechanism underlying pexidartinib-induced hepatotoxicity and clinical safe medication of pexidartinib. - Source: PubMed
Publication date: 2026/01/23
Wang ZhenLv XinYin HangJiang LiliLi WenliLiu Yong