UGT1A10

更新于：2025-05-07

基本信息

别名

GNT1、UDP glucuronosyltransferase family 1 member A10、UDP-glucuronosyltransferase 1-10

+ [10]

简介

UDP-glucuronosyltransferase (UGT) that catalyzes phase II biotransformation reactions in which lipophilic substrates are conjugated with glucuronic acid to increase the metabolite's water solubility, thereby facilitating excretion into either the urine or bile (PubMed:12181437, PubMed:18004212, PubMed:18052087, PubMed:18674515, PubMed:18719240, PubMed:19545173, PubMed:23288867, PubMed:26220143, PubMed:15231852, PubMed:21422672). Essential for the elimination and detoxification of drugs, xenobiotics and endogenous compounds (PubMed:12181437, PubMed:18004212). Catalyzes the glucuronidation of endogenous estrogen hormones such as estradiol, estrone and estriol (PubMed:18719240, PubMed:23288867, PubMed:26220143). Involved in the glucuronidation of arachidonic acid (AA) and AA-derived eicosanoids including 15-HETE and PGB1 (PubMed:15231852). Involved in the glucuronidation of the phytochemical ferulic acid at the phenolic or the carboxylic acid group (PubMed:21422672). Also catalyzes the glucuronidation of the isoflavones genistein, daidzein, glycitein, formononetin, biochanin A and prunetin, which are phytoestrogens with anticancer and cardiovascular properties (PubMed:18052087, PubMed:19545173). Involved in the glucuronidation of the AGTR1 angiotensin receptor antagonist losartan, caderastan and zolarsatan, drugs which can inhibit the effect of angiotensin II (PubMed:18674515). Lacks UGT glucuronidation activity but acts as a negative regulator of isoform 1.

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100 项与 UGT1A10 相关的临床结果

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100 项与 UGT1A10 相关的转化医学

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0 项与 UGT1A10 相关的专利（医药）

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254

项与 UGT1A10 相关的文献（医药）

2025-06-01·Journal of Pharmaceutical and Biomedical Analysis

Identification of human UDP-glucuronosyltransferases involved in I3,II8-biapigenin glucuronidation in Vitro

Article

作者: Song, Jin-Ling ; Li, Ming ; Sun, Xing ; Sun, Hua ; Li, Wei

I3,II8-biapigenin is a biflavonoid compound with diverse pharmacological effects. The present study aimed to investigate the glucuronidation of I3,II8-biapigenin in the human liver microsomes (HLMs) and recombinant human UDP-glucuronosyltransferases (UGTs). Three glucuronidation metabolites of I3,II8-biapigenin were detected in HLMs. Both recombinant human UGTs and chemical inhibitors studies demonstrated that UGT1A1, UGT1A3, UGT1A9 and UGT1A10 were involved in the glucuronidation of I3,II8-biapigenin. The present investigation provided information for the drug-drug interaction potentials of I3,II8-biapigenin when co-administrated with UGTs inhibitors or inducers.

2025-01-01·YAKUGAKU ZASSHI

Precision Medicine for Patients with Renal Cell Carcinoma Based on Drug-metabolizing Enzyme Expression Levels

Article

作者: Matsumoto, Jun

Notable advances have recently been achieved in drug therapies for renal cell carcinoma (RCC). Several tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) have been approved for metastatic RCC (mRCC). The current first-line treatment for mRCC involves combination therapies using TKIs and ICIs. However, there is no consensus on which TKI+ICI therapy is best or how to select the appropriate therapy for individual patients with RCC. The kidney expresses various metabolic enzymes, including CYP and uridine diphosphate glucose (UDP)-glucuronosyltransferase (UGT). Although information on CYP and UGT expression in the kidney is limited compared to our understanding of liver expression, the main CYP and UGT subtypes expressed at high levels in the kidney are estimated to be CYP2B6, CYP3A5, CYP4A11, CYP4F2, UGT1A6, UGT1A9, and UGT2B7. In RCC, the expression profiles and levels of these enzymes are somewhat altered compared with normal kidney. The main known subtypes of CYP and UGT in RCC are CYP1B1, CYP3A5, CYP4A11, UGT1A6, UGT1A9, UGT1A10, and UGT2B7. High CYP expression has been reported in several cancers, possibly conferring resistance to anti-cancer drugs including TKIs, due to extensive drug metabolism. Additionally, CYP and UGT expression levels may possibly affect cancer prognosis by metabolizing endogenous substrates, regardless of their role in anti-cancer drug metabolism. In this review, I discuss CYP and UGT expression level profiles in RCC based on previously published papers, including ours, and examine possible relationships between these enzyme expression profiles and treatment outcomes for patients with RCC.

2024-08-01·Pharmaceutical Research

Comparison of Relative Activity versus Relative Expression Factors (RAF versus REF) in Predicting Glucuronidation Mediated Drug Clearance Using Recombinant UGTs

Article

作者: Prasad, Bhagwat ; Shaikh, Sahil ; Deshmukh, Sujal ; Patel, Mitesh ; Subash, Sandhya ; Ahire, Deepak ; Singh, Dilip Kumar

PURPOSEPredicting the quantitative fraction of glucuronidation (f_gluc) by individual UDP-glucuronosyltransferase enzymes (UGTs) is challenging due to the lack of selective inhibitors and inconsistent activity of recombinant UGT systems (rUGTs). Our study compares the relative expression versus activity factors (REF versus RAF) to predict f_gluc based on rUGT data to human liver and intestinal microsomes (HLM and HIM).METHODSREF scalars were derived from a previous in-house proteomics study for eleven UGT enzymes (UGT1A1, UGT1A3, UGT1A4, UGT1A6, UGT1A9, UGT1A10, UGT2B4, UGT2B7, UGT2B10, UGT2B15, and UGT2B17), whereas RAF was calculated by measuring activities in rUGTs to microsomes of selective UGT probe substrates. Protein-normalized activity factor (pnAF) values were generated after correcting activity of individual UGTs to their corresponding protein abundance. The utility of REF and RAF in predicting f_gluc was assessed for three UGT substrates-diclofenac, vorinostat, and raltegravir.RESULTSThe REF values ranged from 0.02 to 1.75, RAF based on activity obtained in rUGTs to HLM/HIM were from 0.1 to 274. pnAF values were ~ 5 to 80-fold, except for UGT2B4 and UGT2B15, where pnAF was ~ 180 and > 1000, respectively. The results revealed confounding effect of differential specific activities (per pmol) of rUGTs in f_gluc prediction.CONCLUSIONThe data suggest that the activity of UGT enzymes was significantly lower when compared to their activity in microsomes at the same absolute protein amount (pmol). Collectively, results of this study demonstrate poor and variable specific activity of different rUGTs (per pmol protein), as determined by pnAF values, which should be considered in f_gluc scaling.

项与 UGT1A10 相关的新闻（医药）

2024-06-13

·精准药物

抗体偶联药物（ADC）常用有效载荷药代动力学性质总结

前言抗体偶联药物（ADC）的有效载荷分为DNA烷化剂、DNA拓扑异构酶抑制剂、微管蛋白破坏剂和RNApolII抑制剂等，除了以肿瘤为适应症的有效载荷，其他作用机制的有效载荷如糖皮质激素等不断出现，使得ADC的适应症由肿瘤扩展到抗炎和自身免疫性疾病等领域。目前上市的ADC的有效载荷数量有限，临床阶段的有效载荷主要包括MMAE、DM1、SN-38、DXd及其衍生物和PBD等，下面我们重点总结了常用的ADC有效载荷的药代动力学特征，包括分布、代谢、排泄、体内PK、药物相互作用等。澳瑞他汀衍生物MMAE和MMAF的药代动力学特征 1 MMAE (Monomethyl auristatin E) MMAE是一种高效细胞毒素，可与微管结合，通过抑制细胞分裂导致细胞周期停滞并引起细胞凋亡。MMAE具有高渗透性，有很强的旁观者效应[1]。 [3H]-MMAE在ICR小鼠、Wistar大鼠、食蟹猴和人血浆蛋白结合率分别为18.8%-28.5%、72.0-73.5%、17.1-18.9%和67.9%-82.2%（表1），血浆蛋白结合率呈现种属依赖性。在1-100 nmol/L浓度下，[3H]-MMAE的大鼠和猴血浆蛋白结合率不随浓度的改变而改变，但小鼠和人血浆蛋白结合率不同浓度下差异明显。体外试验表明MMAE的人全血血浆分配比为0.79-0.98[2]。表1. MMAE的小鼠、大鼠、猴和人血浆蛋白结合率[3] 接种了MDA-MB-468乳腺癌细胞的荷瘤小鼠在静脉给药0.1 mg/kg的MMAE后，MMAE浓度在血浆中迅速下降，给药5 min后血浆中仅剩注射剂量的0.3%，12 h后血药浓度低于定量下限(0.2 ng/mL)。MMAE的血浆AUC0-12h为54.3ng·h/mL，AUC0-last为54.5 ng·h/mL，系统清除率CL为60 mL/h，血浆末端清除半衰期为2.5 h，稳态分布体积Vdss为42 mL。与血浆相比，MMAE在组织中浓度下降较缓，在肿瘤中能维持较稳定的水平，至给药后168 h组织中浓度降低了50%，MMAE集中分布在肝脏[4]。静脉注射0.06 mg/kg的[3H]-MMAE后，雄性和雌性Sprague Dawley (SD)大鼠全血和血浆中放射性活度随时间变化曲线见图1[3]。图1. 静脉注射0.06mg/kg的[3H]-MMAE后，雄性（左）和雌性（右）SD大鼠全血和血浆中放射性活度随时间变化曲线 MMAE的代谢主要由CYP3A4介导，CYP2D6可能也参与其中。在体外大鼠、猴、人肝细胞中，以及人临床样品中共检测到13种代谢物，推测结构式以及代谢途径如图2所示。基于体内外试验，MMAE在人体内主要发生脱甲基、脱氢、酰胺水解和氧化代谢。MMAE在大鼠、猴和人肝细胞中孵育240分钟后，共检测到12个代谢产物。这12种代谢产物在猴种属中均能检出，有9种代谢产物在人种属中检出。3个种属中M4（O-脱甲基产物）和M6（羟化产物）信号较强，提示为主要代谢物。人种属中未检测到特有的代谢物。体外细胞毒性结果表明M7和M4的细胞毒性远小于MMAE，而M8的细胞毒性与MMAE较为接近，即细胞毒性M7<

抗体药物偶联物临床结果临床1期