Ask about this productRelated genes to: SLC22A12 antibody
- Gene:
- SLC22A12 NIH gene
- Name:
- solute carrier family 22 member 12
- Previous symbol:
- -
- Synonyms:
- OAT4L, RST, URAT1
- Chromosome:
- 11q13.1
- Locus Type:
- gene with protein product
- Date approved:
- 2002-07-31
- Date modifiied:
- 2016-02-18
Related products to: SLC22A12 antibody
Related articles to: SLC22A12 antibody
- Hyperuricemia, characterized by elevated serum uric acid (SUA) levels, is increasingly recognized as a significant contributor to cardiometabolic diseases including hypertension, type 2 diabetes, chronic kidney disease, metabolic syndrome, and atherosclerotic cardiovascular disease. In the past, uric acid was seen mainly as a byproduct of purine metabolism linked to gout. However, growing evidence suggests that it plays an active role in causing metabolic and vascular dysfunction. Mechanistic studies have shown that higher uric acid levels can induce endothelial dysfunction, oxidative stress, inflammation, insulin resistance, and activation of the renin-angiotensin-aldosterone system, which together can worsen cardiometabolic conditions. Recent advances in high-throughput omics technologies have greatly improved understanding of the molecular mechanisms regulating uric acid metabolism. Genome-wide association studies (GWAS) have identified important urate transporter genes like SLC2A9, ABCG2, and SLC22A12, while epigenomic studies reveal how DNA methylation, histone changes, and non-coding RNAs connect genetic factors to environmental influences. Transcriptomic and single-cell RNA sequencing analyses explain how urate transport and inflammatory signaling are regulated in specific tissues, including the kidneys, liver, adipose, and vascular tissue. In parallel, metabolomic and proteomic studies have linked hyperuricemia to disruptions in purine metabolism, redox balance, lipid remodeling, and inflammatory protein networks. Together, multi-omics approaches that integrate genomics, epigenomics, transcriptomics, proteomics, and metabolomics, along with expression quantitative trait locus (eQTL) mapping, causal modeling, network biology, and AI analysis, now provide powerful tools for biomarker discovery and mechanistic interpretation. This review summarizes current insights into uric acid metabolism from a multi-omics perspective and highlights emerging opportunities for better risk assessment, biomarker discovery, therapeutic targeting, and tailored prevention strategies in cardiometabolic disease. - Source: PubMed
Publication date: 2026/05/25
Ali Nurshad - Gout and hyperuricemia, caused by high serum uric acid, require safer and more effective treatments due to the toxicity and limited efficacy of current drugs. Dual inhibition of URAT1 and GLUT9 may reduce renal toxicity compared to single-target approaches. Starting from lead compound , we used scaffold hopping and structure-guided design to develop 46 novel polycyclic pyrimidine derivatives. Among these, compound showed potent and balanced inhibition of URAT1 (IC = 4.01 μM) and GLUT9 (IC = 1.60 μM), greatly improving upon . Additionally, reduced serum uric acid levels by 82.4% in hyperuricemic mice, while it exhibited favorable pharmacokinetic profiles in rats ( = 33.71 vs 20.13% for ). Significantly, was efficacious at a low dose (0.5 mg/kg) and showed no acute toxicity at 1000 mg/kg. These results support as a promising dual URAT1/GLUT9 inhibitor with improved efficacy, pharmacokinetics, and safety for treating gout and hyperuricemia. - Source: PubMed
Publication date: 2026/05/06
Yang QianQi DanhuiYe WenjieShi XiaoyuYang MingyuWu TingWu ZhenkunXu YuexinWang YouzhaoXu ShujingWang ZhenqianGao ShenghuaYi FanPang JianxinLiu XinyongZhan Peng - Uricase-based drugs excel at treating refractory hyperuricemia and tumor lysis syndrome by directly degrading uric acid but are limited by immunogenicity. Here, we engineered RAW264.7 macrophages with ectopic co-expression of Aspergillus flavus uricase and murine urate anion transporter 1 (URAT1), forming a "transport-degradation" system: URAT1 actively transports uric acid into cells for intracellular degradation. Recombinant lentiviral vectors carrying target genes were transfected into RAW264.7 cells, followed by puromycin screening. In vitro assays showed that the engineered macrophages nearly completely degraded uric acid (from 556.0 ± 37.0 μmol/L to 0.7 ± 0.6 μmol/L) at 72 h. URAT1 inhibition with benzbromarone abolished uric acid degradation in URAT1-expressing cells. In both acute dietary-induced and chronic genetic hyperuricemic mouse models, RAW-afUri-URAT1 exerted robust and sustained uric acid-lowering activity, maintaining serum uric acid at 77.14 ± 37.48 μmol/L on day 16 in yeast extract gavaged mice and normalizing serum uric acid to 76.2 ± 15.9 μmol/L in liver uricase conditional knockout mice, both significantly superior to the rebound levels observed in mice treated with Rasburicase (143.19 ± 38.21 μmol/L and 142.4 ± 17.4 μmol/L, respectively; P < 0.05). Safety assessments in dietary-induced hyperuricemia mice showed no obvious abnormalities in liver or renal function, and significantly reduced hyperuricemia-related production of inflammatory cytokines (IL-1β, IL-6, TNF-α), Immunogenicity assays showed undetectable anti-uricase antibodies in RAW-afUri-URAT1 treated mice but high level of antibodies in rasburicase treated mice. This engineered macrophage system shows potent, durable uric acid-lowering efficacy, with low immunogenicity and good biosafety, offering a promising strategy for hyperuricemia therapy. - Source: PubMed
Publication date: 2026/04/20
Feng YuzhongCui JiazhenHuang XuanLi YupengDong HaolongXiong XianghuaLiu GangWang QingyangChen Huipeng - Hyperuricemia and gout remain challenging due to the limited efficacy and safety of current therapies. Herein, we report a novel pyrrole acylsulfonamide, compound , rationally designed via structural simplification of lead compounds and , targeting urate transporters. In acute hyperuricemia mice, compound demonstrated potent urate-lowering efficacy with a decrease ratio of 88.76%, significantly superior to Lesinurad (39.02%). Mechanistically, it synergistically inhibited URAT1 (IC = 2.81 ± 0.40 μM) and GLUT9 (IC = 12.53 ± 1.33 μM), with reduced off-target activity on OAT1 (IC = 7.83 ± 0.70 μM vs 's 4.90 ± 0.99 μM) to mitigate potential toxicity. It displayed superior ligand efficiency (LE = 0.44 vs 's 0.41) and favorable pharmacokinetics ( = 5.55 h, = 51.3%). In hyperuricemic nephropathy mice, compound reduced serum uric acid and protected renal function without acute and subacute toxicity at high doses, supporting its promise as a candidate for hyperuricemia and gout. - Source: PubMed
Publication date: 2026/04/17
Wang ZhenqianShi XiaoyuGuo ZitaoWu ZhenkunXu YuexinYang MingyuWang MeiYang QianWu TingPang JianxinYi FanZhan PengLiu Xinyong - To investigate the genetic architecture of low-frequency and rare variants of serum urate (SU) in East Asian populations, and to clarify its role as a heritable and modifiable risk factor for gout and cardiometabolic diseases. - Source: PubMed
Publication date: 2026/03/24
Tan QilongZhou HanyiJia JunlinCui JiamengSun LiyangZheng WeifangTu HuakangXu XiaohangWang MengyingZhou DanLi WenyuanWu Xifeng