Ask about this productRelated genes to: UGT1A4 antibody
- Gene:
- UGT1A4 NIH gene
- Name:
- UDP glucuronosyltransferase family 1 member A4
- Previous symbol:
- -
- Synonyms:
- HUG-BR2, UGT1D
- Chromosome:
- 2q37.1
- Locus Type:
- complex locus constituent
- Date approved:
- 2000-06-22
- Date modifiied:
- 2016-03-01
Related products to: UGT1A4 antibody
Related articles to: UGT1A4 antibody
- : Tamoxifen is widely used in the treatment of hormone receptor-positive breast cancer and has been shown to successfully reduce recurrence and mortality rates. Nonetheless, variability in patient response to tamoxifen treatment is observed with up to 40% of patients experiencing recurrence. Genetic polymorphisms in pharmacogenes encoding enzymes involved in tamoxifen metabolism have been linked to some of this observed interindividual variability. The pharmacogenetics of tamoxifen in populations of African descent remain understudied, creating difficulties in pinpointing the primary factors behind the observed variable response. To address this gap, this study aimed to investigate the role of genetic variation in tamoxifen treatment outcomes in a South African cohort. : Participants included 166 Mixed and African Ancestry breast cancer patients who had received tamoxifen treatment. Genetic characterization was performed for 53 single nucleotide polymorphisms (SNPs) and two copy number variations across eight drug-metabolizing enzymes, including cytochrome P450s (, , , ), UDP-glucuronosyltransferases (), and sulfotransferases (, , ). The association between genotypes and disease-free survival (DFS) was evaluated using Cox proportional hazards regression models. : The or * genotype showed a nominal association with improved DFS ( = 0.049), with a similar trend observed for rs11888492. In contrast, rs3775779 heterozygosity showed a nominal association with reduced DFS ( = 0.044). SNPs (rs4149393, rs4149394, rs1042157) demonstrated trends toward reduced DFS. : These exploratory findings highlight the need for more inclusive pharmacogenomic research and point to potential biomarkers for optimizing tamoxifen therapy in African populations. - Source: PubMed
Publication date: 2026/03/31
Kruger BiancaChimusa Emile RAbera Aron BSingh JesmikaShamley DelvaDandara Collet - - Source: PubMed
Publication date: 2026/04/24
Sangüesa EstelaCirujeda ChristineBernal AnaRibate María PilarGarcía Cristina Belén - While pregnancy-related changes in phase I enzyme activity are well-documented, less is known about the impact on phase II enzymes. This study aimed to test the hypothesis that changes in the pharmacokinetics (PK) of uridine 5'-diphosphoglucuronosyltransferase (UGT) substrates during pregnancy result from altered enzyme expression or activity. Physiologically based PK (PBPK) modelling was used to evaluate these changes in pregnant populations. - Source: PubMed
Publication date: 2026/04/15
Saffaf Williamvan der Velde YmkeMalik Paul R VPrins Jelmer RGordijn Sanne JTouw Daan JMian Paola - Uridine diphosphate (UDP)-glucuronosyltransferases (UGTs) are a family of enzymes with highly similar amino acid sequences, making it challenging to distinguish between their roles. Developing selective probes and inhibitors is essential for understanding the unique functions of each isoform. In this study, we synthesized four novel naphthalimide-based fluorescent probes bearing nitrogen-containing substituents at the 4-position and identified -butyl-4-methylpiperazine-1,8-naphthalimide (BAD3) as a highly selective and sensitive substrate for UGT1A4. Using BAD3, we established an inhibitor screening platform and identified ursolic acid (T7) as a promising lead compound from a natural product library. Structure-activity relationship (SAR) studies revealed that esterification at the 3-hydroxyl group significantly enhanced inhibitory activity, yielding two potent inhibitors, T25 and T26, while modifications at the 28-carboxyl group reduced activity. Further characterization confirmed T25 (inhibition constant ( ) = 0.64 μM) and T26 ( = 0.61 μM) as selective and competitive UGT1A4 inhibitors. Molecular docking revealed that the 28-carboxyl group plays a crucial role by forming a salt bridge with Arg258 in the UGT1A4 active site. studies demonstrated that T25 significantly altered the pharmacokinetic profile of BAD3, confirming its inhibitory effect on UGT1A4 in animals. Together, BAD3 and the selective inhibitors T25/T26 serve as valuable molecular tools for studying the physiological and pharmacological roles of UGT1A4. - Source: PubMed
Publication date: 2025/07/26
Mao NingLi Shi-QingZhou Xiang-LuHu CongWu Wen-ChaoWei HuaZou Li-WeiYang Ling - : Tamoxifen remains the cornerstone of endocrine therapy for hormone receptor-positive breast cancer across Africa. Understanding the factors that influence tamoxifen tolerability is critical, as treatment-related side effects can reduce adherence and compromise therapeutic outcomes. Yet, the contribution of pharmacogenetic variation to tamoxifen-related toxicity remains poorly characterized in African populations. This study, therefore, investigated whether genetic variation in key pharmacogenes influences the risk of treatment-related side effects in a South African breast cancer cohort. : A total of 166 women of Mixed and African Ancestry treated with 20 mg/day tamoxifen at Groote Schuur Hospital, South Africa, were included in the study. Genetic variation across 28 variants in nine pharmacogenes, including , , , , , and , was assessed using various genotyping methods. Associations between genetic and non-genetic factors and tamoxifen side effects were evaluated with logistic regression. : Over 70% of participants reported at least one treatment-related side effect. Overall side-effect burden was associated with copy number variation ( = 0.030) and rs3736599 ( = 0.042). Musculoskeletal complaints were the most common (40%) and were associated with rs7439366 ( = 0.040) and rs2242480 ( = 0.051). Gynecological symptoms affected more than 20% of participants and were linked to ( = 0.050), rs3736599 ( = 0.016), and rs4148269 ( = 0.039). Hot flashes were frequent, affecting 33% of patients, but showed no clear pharmacogenetic associations. : This study demonstrates that pharmacogenetic variation is associated with interindividual differences in treatment-related side effects, underscoring the need to expand research in African populations to better inform precision endocrine therapy. - Source: PubMed
Publication date: 2026/02/24
Kruger BiancaChimusa EmileAbera AronSingh JesmikaShamley DelvaDandara Collet