Ask about this productRelated genes to: SLC5A11 Blocking Peptide
- Gene:
- SLC5A11 NIH gene
- Name:
- solute carrier family 5 member 11
- Previous symbol:
- -
- Synonyms:
- KST1, SMIT2, SGLT6
- Chromosome:
- 16p12.1
- Locus Type:
- gene with protein product
- Date approved:
- 2004-03-23
- Date modifiied:
- 2016-02-17
Related products to: SLC5A11 Blocking Peptide
Related articles to: SLC5A11 Blocking Peptide
- Currently, there are no effective drug treatments for aging. Mendelian randomization (MR) has been widely applied to repurpose existing drugs and identify new therapeutic targets. Our aim is to identify aging-related therapeutic targets and evaluate their potential adverse effects, underlying mechanisms, and actionable drugs. - Source: PubMed
Publication date: 2026/03/29
Zhang YanfangWang MenglongLi HangJin TingPeng ShanshanDong YiDeng ChaoweiLi HangLi XinyiQin JuanjuanYe Xujun - Metformin exhibits immunomodulatory properties in cancer treatment, but the underlying mechanisms remain elusive. Using genome-wide CRISPR screening, we identified SLC5A11 as an essential mediator of metformin sensitivity. Molecular docking and dynamics simulations revealed direct metformin-SLC5A11 binding at the pocket containing Asn78 and Glu102 residues. Metformin suppressed PD-L1 expression across multiple cancer models through SLC5A11-dependent activation of AMPK and subsequent JAK2-STAT1-IRF1 downregulation. SLC5A11 knockout abolished these effects, while reconstitution restored metformin responsiveness. In syngeneic mouse models of lung and pancreatic cancer, combining metformin with anti-PD1 therapy produced synergistic antitumor effects, enhanced T cell infiltration, and potentiated immunotherapy efficacy. Metformin pretreatment significantly enhanced PBMC-mediated cytotoxicity against tumor cells and patient-derived organoids in ex vivo co-culture systems. Our findings establish the SLC5A11-AMPK-PD-L1 axis as a novel mechanism linking metformin to tumor immunity, providing a molecular rationale for combining metformin with checkpoint inhibitors in cancer immunotherapy. - Source: PubMed
Publication date: 2026/02/12
Ma YaruiWang XueWei ZhewenZhang QiYuan FangqingXu ChunguiLiu ChangWang XiaobingLi LinJiao Yuchen - Despite the importance of the gut microbiome to health, the role of human genetic variation in shaping its composition remains poorly understood. Here we report genome-wide association analyses of harmonized metagenomic data from 16,017 adults in four Swedish population-based studies, with replication in 12,652 people from the Norwegian HUNT study. We identified variants in the OR51E1-OR51E2 locus, encoding sensors for microbiome-derived fatty acids, associated with microbial richness. We further identified 15 study-wide significant genetic associations (P < 5.4 × 10) involving eight loci and 14 common bacterial species, of which 11 associations at six loci were replicated. The results confirm previously reported associations at LCT, ABO and FUT2, and provide evidence for new loci MUC12, CORO7-HMOX2, SLC5A11, FOXP1 and FUT3-FUT6, with supporting data from metabolomics and gene expression analyses. Our findings link gut microbial variation genetically to gastrointestinal functions, including enteroendocrine fatty acid sensing, bile composition and mucosal layer composition. - Source: PubMed
Publication date: 2026/02/13
Dekkers Koen FPertiwi KamalitaBaldanzi GabrielLundmark PerHammar UlfMoksnes Marta RiiseCoward EivindNethander MariaSalih Ghassan AliMiari MariamNguyen DiemSayols-Baixeras SergiEklund Aron CHolm Jacob BakNielsen H BjørnVolpiano Camila GazollaMéric GuillaumeThangam ManonanthiniHakaste LiisaTuomi TiinamaijaAhlqvist EmmaSmith Christopher AAllen MarieReimann FrankGribble Fiona MOhlsson ClaesHveem KristianMelander OlleNilsson Peter MEngström GunnarSmith J GustavMichaëlsson KarlÄrnlöv JohanOrho-Melander MarjuFall Tove - Obesity is an epidemic with myriad health effects, but little is understood regarding individual obese phenotypes and how they may respond to therapy. Epigenetic changes associated with obesity have been detected in blood, liver, pancreas, and adipose tissues. Previous work using human organoids found that dietary glucose hyperabsorption is a steadfast trait in cultures derived from some obese subjects, but detailed transcriptional or epigenomic features of the intestinal epithelia associated with this persistent phenotype are unknown. This study evaluated differentially expressed genes and relative chromatin accessibility in intestinal organoids established from donors classified as non-obese, obese, or obese hyperabsorptive by body mass index and glucose transport assays. Transcriptomic analysis indicated that obese hyperabsorptive subject organoids have significantly upregulated dietary nutrient absorption transcripts and downregulated type I interferon targets. Chromatin accessibility and transcription factor footprinting predicted that enhanced HNF4G binding may promote the obese hyperabsorption phenotype. Quantitative RT-PCR assessment in organoids representing a larger subject cohort suggested that intestinal epithelial expression of CUBN, GIP, SLC5A11, and SLC2A5 were highly correlated with hyperabsorption. Thus, the obese hyperabsorption phenotype was characterized by transcriptional changes that support increased nutrient uptake by intestinal epithelia, potentially driven by differentially accessible chromatin. Recognizing unique intestinal phenotypes in obesity provides a new perspective in considering therapeutic targets and options with which to manage the disease. - Source: PubMed
Publication date: 2025/10/08
Badurdeen Dilhana SLi ZhenLee Jeong-HeonMa TaoBhagwate Aditya VijayLatanich RachelDogiparthi ArjitOrdog TamasKovbasnjuk OlgaKumbhari VivekFoulke-Abel Jennifer - Identifying the molecular targets of toxic compounds remains a major challenge in toxicology, particularly when adverse effects occur in off-target organs and the mechanism of action is unknown. To address this issue, a comprehensive computational pipeline was developed to perform high-throughput molecular docking across the entire AlphaFold2-predicted structural proteome of representative organisms such as human and mouse, followed by enrichment analysis to estimate biological processes potentially affected by ligand binding. The pipeline was first evaluated using six known drug-target pairs. In several cases, the known targets were ranked between the top 2 and 250 proteins (top 0.009-1.15%) among more than 21,000 proteins, and displayed docking poses consistent with experimentally observed binding conformations. However, performance was limited for certain targets, such as carbonic anhydrase II with acetazolamide, where the binding pocket was broad, leading to inaccurate docking results. The pipeline was subsequently applied to puberulic acid, a compound suspected of causing severe nephrotoxicity. Screening identified sodium/myo-inositol cotransporter 2 (SLC5A11) as a high-affinity target in both human and mouse, suggesting a mechanism involving disruption of renal osmoregulation. Although docking scores represent only theoretical binding estimates and do not directly imply physiological effects, their distribution was independent of protein length and AlphaFold2 confidence scores (pLDDT), supporting the methodological robustness. This in silico framework enables hypothesis-driven identification of potential target proteins for toxicants or therapeutics and offers a useful tool for predictive toxicology, particularly when experimental data are limited. The pipeline is available at: https://github.com/toxtoxcat/reAlldock. - Source: PubMed
Hayama TeppeiSugawara RinKamata RyoSekijima MasakazuTakeda Kazuki