Ask about this productRelated genes to: UGT1A1 Blocking Peptide
- Gene:
- UGT1A1 NIH gene
- Name:
- UDP glucuronosyltransferase family 1 member A1
- Previous symbol:
- UGT1, GNT1
- Synonyms:
- UGT1A
- Chromosome:
- 2q37.1
- Locus Type:
- complex locus constituent
- Date approved:
- 1989-02-13
- Date modifiied:
- 2019-04-23
Related products to: UGT1A1 Blocking Peptide
Related articles to: UGT1A1 Blocking Peptide
- Fraxetin (7,8-dihydroxy-6-methoxycoumarin), a coumarin constituent of Cortex Fraxini (Qinpi) used in traditional Chinese medicine, is metabolised mainly by UGT1A9, but its potential to inhibit UGT enzymes and cause herb-drug interactions (HDIs) is largely unstudied. Fraxetin and four related coumarins were screened against 11 recombinant human UGTs; isoforms inhibited ≥80% underwent full kinetic analysis with 4-methylumbelliferone as probe. Binding was examined by molecular docking on AlphaFold structures with PLIP, triplicate 100 ns molecular dynamics, and MM/GBSA and MM/PBSA free-energy calculations, and interaction risk by FDA 2020 in vitro-in vivo extrapolation (IVIVE). Fraxetin alone inhibited both UGT1A1 and UGT1A9 by >80% and was characterised in detail, acting as a mainly competitive mixed-type inhibitor (UGT1A1 IC 15.99 μM, 8.32 μM; UGT1A9 IC 8.44 μM, 5.90 μM). A structure-activity comparison identified a dual-element pharmacophore comprising the C-6 methoxy group and the 7,8-dihydroxycoumarin aglycone. MM/GBSA favoured UGT1A9 over UGT1A1 (ΔΔ = -4.06 kcal/mol, = 0.005), concordant with the kinetic ranking. IVIVE predicted a borderline systemic signal ( > 1.02) but an intestinal approximately five- to seven-fold above the high-risk threshold of 11 after capping the luminal concentration at fraxetin aqueous solubility. This is the first characterisation of fraxetin as a moderate-potency inhibitor of UGT1A1 and UGT1A9 and points to a previously under-recognised herb-drug interaction risk concentrated in the intestinal lumen rather than systemically; the finding constitutes an interaction signal requiring clinical confirmation rather than an established risk. - Source: PubMed
Publication date: 2026/06/22
Chen JinqianHan HanLi JibinXu SimengLi XichuanZhao Zhenyu - Metabolic syndrome (MetS) is a cluster of risk factors increasing the likelihood of cardiovascular and metabolic diseases. This study investigated the relative mRNA expression of key hepatic and intestinal phase II drug-metabolising enzymes, specifically UDP-glycosyltransferases (UGTs) and sulfotransferases (SULTs), in four non-obese rat models of MetS characterised by different dominant traits: the hereditary hypertriglyceridaemic (HHTg) rat, spontaneously hypertensive rat (SHR), SHR-expressing transgenic human C-reactive protein (SHR-CRP) rat, and bilaterally ovariectomised female Wistar (W-OVX) rat, compared to Wistar controls. Gene expression was quantified by RT-PCR with data normalised using the ΔΔCt method. Measurements showed significant model-specific differences, especially in the liver. HHTg rats exhibited significant hepatic suppression of (-90%) and undetectable transcripts, alongside compensatory upregulation of (196%) and (277%). The SHR model showed significant hepatic upregulation of (330%), (266%), and (328%). Chronic inflammation in SHR-CRP rats caused a significant decrease in hepatic , whereas a significant induction occurred in the intestine. Oestrogen deprivation (W-OVX) led to significant downregulation of hepatic and . These findings highlight that the alterations in phase II metabolism strongly depend on the pathophysiological context, potentially affecting drug disposition in preclinical models. - Source: PubMed
Publication date: 2026/05/27
Soukop JanPoruba MartinRácová ZuzanaZapletalová IvetaMalínská HanaHüttl MartinaMarková IrenaVečeřa Rostislav - Digeda-8 (DGD8) is a traditional polyherbal formulation with a long history of clinical use in Mongolian medicine for the treatment of hepatobiliary disorders and cholestatic conditions. Despite its traditional reputation, the pharmacological basis and molecular mechanisms underlying its effects against cholestatic liver injury (CLI) remain scientifically uncharacterized. - Source: PubMed
Publication date: 2026/06/24
Bayoude AlamusiYi RiguiZhao YuyingRuna AMing MingHu SileJirimu Batu - Crigler-Najjar syndrome type 1 (CN1) causes complete UGT1A1 deficiency, lifelong severe unconjugated hyperbilirubinemia, and persistent risk of bilirubin-induced neurologic dysfunction. We present a 21-year-old woman with genetically confirmed CN1 who developed acute-on-chronic hyperbilirubinemia to 30 mg/dL during hospitalization for enteritis when her home high-intensity phototherapy system was unavailable. Systematic optimization of inpatient phototherapy using multiple high-irradiance units with simultaneous dorsal and ventral coverage produced a 7.5 mg/dL bilirubin reduction within 12-18 hours, deferring planned therapeutic plasma exchange entirely. This case highlights phototherapy inadequacy as a correctable, underrecognized driver of acute decompensation in hospitalized adult CN1 patients. - Source: PubMed
Publication date: 2026/06/22
Vattoth Ahamed LazimNarayanan Praveena - PF-06835919, a ketohexokinase inhibitor intended for the treatment of non-alcoholic fatty liver disease, caused decreased/absent corpora lutea in the ovary in a 6-month rat repeat-dose toxicity study. These findings occurred in the presence of liver and thyroid effects, and it was hypothesized that the decreased/absent corpora lutea was due to hypothyroidism secondary to PF-06835919-related UGT (UDP-glucuronosyltransferase) enzyme induction. An investigative study was conducted to evaluate the onset of ovarian changes by monitoring daily estrous cycles with daily administration of 100 mg/kg/day, and thyroid hormone levels were also measured. Estrous cycle disruption (persistent estrus) was noted in 10 of 15 females, with onset occurring between days 33 and 81. Higher TSH (3.8x control) and altered T3 and T4 were noted on day 37, indicating that thyroid hormone dysregulation preceded the estrous cycle disruption. Recovery of the estrous cycle disruption occurred in 30% of the animals before the study was terminated due to onset of reproductive senescence. Liver UGT enzyme induction, including UGT1A1, was confirmed to be induced in a separate 2-week rat study. All available data support the hypothesis that PF-06835919-related induction of one or more UGT enzymes and consequent thyroid dysregulation were the cause of ovarian changes in the rat. - Source: PubMed
Publication date: 2026/06/19
Campion Sarah NBowman Christopher JHoule ChristopherQian JessieZhou JunCook Jon