Ask about this productRelated genes to: UGT2B4 antibody
- Gene:
- UGT2B4 NIH gene
- Name:
- UDP glucuronosyltransferase family 2 member B4
- Previous symbol:
- -
- Synonyms:
- UGT2B11
- Chromosome:
- 4q13.3
- Locus Type:
- gene with protein product
- Date approved:
- 1997-07-01
- Date modifiied:
- 2016-03-01
Related products to: UGT2B4 antibody
Related articles to: UGT2B4 antibody
- Uridine diphosphate glucuronosyltransferase 2B () enzymes constitute a critical subgroup of phase II metabolizing enzymes that modulate the clearance of steroid hormones, carcinogens, and numerous anticancer agents, thereby influencing cancer susceptibility, progression, and therapeutic outcomes. This review provides a comprehensive synthesis of the genetic, regulatory, and functional roles of family members, particularly , , , , , and , in oncogenesis and cancer treatment. We summarize evidence from molecular, epidemiological, pharmacogenetic, and clinical studies demonstrating how expression patterns, polymorphisms, copy number variations, epigenetic regulation, and microRNA-mediated control shape intratumoral hormone homeostasis, carcinogen detoxification, and drug resistance across multiple malignancies, including prostate, breast, lung, colorectal, hematological, and hormone-dependent cancers. enzymes metabolize several widely used anticancer drugs and active metabolites, thereby affecting pharmacokinetics, efficacy, and toxicity. Understanding the context-specific roles of family members offers a compelling opportunity for therapeutic exploitation. In particular, rational combination strategies incorporating inhibitors or modulators alongside standard anticancer agents may enhance drug effectiveness without increasing dosage, while simultaneously enabling the dose reduction of the partner agent to mitigate dose-dependent toxicities. Such approaches are especially relevant for therapies with narrow therapeutic indices. Overall, this review highlights enzymes as multifunctional determinants of cancer risk and treatment response and underscores their promise as biomarkers and actionable targets for precision oncology and optimized combination regimens. - Source: PubMed
Publication date: 2026/06/30
Srinivasamurthy Suresh KumarSamuel Vijaya PaulHakim Tarig Hakim MerghaniGeorge Biji ThomasBernardt Grisilda VidyaKamath AshwinUppugunduri Chakradhara Rao Satyanarayana - Cenobamate (CNB) demonstrates high efficacy in drug-resistant focal epilepsy, yet optimal management requires personalized strategies. This exploratory case series describes five patients selected from a cohort of 125 individuals treated with CNB, examining the relationship between pharmacogenetic (PGx) profiles and clinical outcomes. Clinical data and therapeutic drug monitoring (TDM) were integrated with targeted Next-Generation Sequencing of key metabolic genes (UGT2B7, UGT2B4, CYP2E1, CYP2B6, CYP2A6, CYP3A4, CYP2C19) to predict metabolizer phenotypes. Three patients (Cases 1, 3, 4) achieved seizure freedom or ≥50% response at sub-target or target doses (100-200 mg/day enabling early de-escalation of concomitant sodium channel blockers and valproate. This success was supported by a proactive digital communication protocol and a mandatory 100 mg clinical checkpoint. Case 2-a non-responder at 400 mg/day despite therapeutic plasma levels (28.22 mg/L)-exhibited a predicted "Ultrarapid Metabolizer" (UM) phenotype characterized by UGT2B7 Haplotype 4 and CYP2E1 duplication, suggesting possible pharmacokinetic contribution to non-response. Case 5 experienced dose-limiting toxicity at 100 mg/day; we hypothesized this toxicity could be driven by a drug-drug-gene interaction involving CNB-mediated inhibition that impairs clearance of N-desmethylclobazam (the active metabolite of clobazam) in a patient with impaired activity and intermediate function. As an exploratory case series, these findings require validation in adequately powered prospective studies. Associations between UM phenotype and non-response, and between PM phenotype and dose-limiting toxicity, represent preliminary observations that may reflect pharmacokinetic variability. Nevertheless, our experience is consistent with a personalized, sub-target dose titration strategy that may help minimize adverse events in complex polypharmacy settings. - Source: PubMed
Publication date: 2026/06/04
d'Orsi GiuseppeDi Claudio Maria TeresaCafaro AlessiaBarco SebastianoRobustella MartaLocatelli NicolòLiantonio AntonellaImbrici PaolaCiavarella GraziaRinaldi AntonioFania GiuseppeCostantino UmbertoCarella MassimoCangemi GiulianaMiscio Giuseppe - Intrahepatic cholestasis of pregnancy (ICP) is a liver disorder with limited treatment options. This study investigated the therapeutic potential of resveratrol (RES) and its underlying mechanisms, focusing on the gut-liver axis and bile acid metabolism in an estrogen-induced ICP rat model. - Source: PubMed
Publication date: 2026/05/18
Hu NingningYang YingChen RujunGuan JunhuaGu HuafenZhang LinglingZhang XuemeiWang XiaoqinZhang Liwen - : With the ongoing efforts in supporting the discovery of novel targeted drug delivery systems for the upper region of the female reproductive tract (FRT), it is imperative to understand the local drug disposition pathways. We aim to obtain a comprehensive profile of the drug transporters and drug-metabolizing enzymes in the human ectocervix, uterus, and fallopian tubes, as these factors may substantially influence mucosal penetration, tissue exposure, drug disposition, and the risk of drug-drug interactions. Gene expression of 12 drug transporters and 21 drug-metabolizing enzymes was quantified using RT-qPCR. Protein expression of highly expressed transporters was assessed using immunohistochemistry (IHC). : Among the 12 transporters analyzed, the efflux transporters P-gp, BCRP, and MRP4 exhibited the highest expression across the ectocervix, endometrium, myometrium, and fallopian tubes, with P-gp consistently showing the greatest abundance in all evaluated FRT tissues. Expression of these transporters was significantly higher (6-17×) in myometrium compared with ectocervix. IHC demonstrated strong localization of P-gp, BCRP, and MRP4 to epithelial layers facing the lumen, as well as to stromal and vascular endothelial cells. For drug-metabolizing enzymes, all 21 phase I and II enzymes were detectable across the FRT, and 15 were expressed at comparatively higher levels across all tissue types. These included CYP1A1, CYP1B1, CYP2B6, CYP2C8, CYP2C19, CYP3A4, UGT1A1, UGT1A3, UGT1A4, UGT1A7, UGT1A8, UGT1A10, UGT2B4, UGT2B15, and UGT2B17. : The gene expression and localization data obtained from this work may improve our understanding of drug disposition in the FRT, which will inform selection, design, and optimization of drugs intended for targeted delivery within the FRT. - Source: PubMed
Publication date: 2026/05/21
Le AnValicherla Guru RZhang JunmeiWang LinDonnelly Mark KBies RobertRohan Lisa C - Pediatric populations differ from adults in drug elimination capacity. While current scaling methods account for enzyme and transporter maturation, they overlook comorbidities, such as biliary atresia (BA), a liver disease appearing within the first 2-8 weeks of life that can progress to cirrhosis. Such conditions may impair hepatic drug clearance, requiring dose adjustments. Physiologically based pharmacokinetic (PBPK) tools aim to address such cases and have been advocated to fill gaps in clinical data instead of less formalized and evidence-based guesswork. However, the paucity of systems data in rare disease populations has hindered the development of robust PBPK models. This study used global liquid chromatography and tandem mass spectrometry (LC-MS/MS) proteomics to quantify drug-metabolizing enzymes and transporters in diseased neonatal (n = 13) and infant (n = 12) liver samples, revealing significant expression changes in biliary atresia (BA) livers vs. controls (n = 19). Based on cohort means, CYP2A6, CYP2B6, and CYP2E1 levels were 6-17-fold higher in BA livers compared to controls, while CYP4F11 and CYP20A1 were reduced. UGT1A1, UGT2B4, and UGT2B7 showed up to 16-fold higher abundance in neonates with BA. Among transporters, ABCF1 abundance increased dramatically (46-fold), whereas B3AT/SLC4A1, ADT1/SLC25A4, and S27A5/SLC27A5 were decreased. The observed alterations suggest that assuming similar liver function in BA and non-BA patients has implications, with impact varying by drug clearance pathway. While in silico models can explore this, clinical pharmacokinetic studies in BA are essential for verification. To our knowledge, such studies are absent. Our observations underscore the urgent need for dedicated pharmacokinetic studies in BA patients to improve precision dosing. - Source: PubMed
Publication date: 2026/03/04
Al-Majdoub Zubida MHoward MartynAchour BrahimBarber JillAlizai NavedRostami-Hodjegan Amin