Ask about this productRelated genes to: Slc6a9 Blocking Peptide
- Gene:
- SLC6A9 NIH gene
- Name:
- solute carrier family 6 member 9
- Previous symbol:
- -
- Synonyms:
- GLYT1
- Chromosome:
- 1p34.1
- Locus Type:
- gene with protein product
- Date approved:
- 1995-10-02
- Date modifiied:
- 2016-10-05
Related products to: Slc6a9 Blocking Peptide
Related articles to: Slc6a9 Blocking Peptide
- There are currently no approved pharmacotherapies to treat cognitive impairment associated with schizophrenia (CIAS). Iclepertin (BI 425809) is a selective glycine transporter-1 (GlyT1) inhibitor that was investigated for the treatment of CIAS. As hemoglobin reduction is considered a class effect of GlyT1 inhibitors, nonclinical studies and clinical trials were assessed to determine if this effect applied to iclepertin. Nonclinical studies of iclepertin-treated rodents demonstrated a reversible reduction in hemoglobin versus vehicle-control animals. Pooled Phase I data from healthy volunteers (N = 391) showed no clinically relevant changes in hemoglobin. Analysis of Phase II, 12-week, randomized-controlled trials in patients with CIAS (N = 709) receiving placebo or iclepertin 2, 5, 10, or 25 mg demonstrated a small hemoglobin decrease in the 10-mg group and, in the 25-mg group, a dose- and pharmacokinetic-dependent, mild hemoglobin decrease that recovered slightly at post-treatment follow-up (Week 16). Pooled data from the Phase III CONNEX trial program, which included three 26-week, randomized-controlled trials (N = 1835), and one 52-week open-label extension (N = 1356) in patients with CIAS, showed that iclepertin was well-tolerated. In placebo-treated patients, hemoglobin concentration was stable, with small fluctuations over 26 weeks. In iclepertin-treated patients, hemoglobin concentration dropped within the first 18 weeks (mean change vs baseline, -2.4 g/L) and remained stable until the end of treatment (≤78 weeks). As the primary and secondary CIAS efficacy endpoints were not met, the CONNEX trial program was terminated. Findings from these nonclinical studies and clinical trials suggest reversible mean hemoglobin reductions were of limited significance and iclepertin was well-tolerated with a consistent safety profile. - Source: PubMed
Nagy PeterFowler Justin CoreyRosenbrock HolgerTang WenboFu EricFraser AnnieDursema HollySchlichtiger JuliaDesch MichaelGruenenfelder Fredrik - Glycine is a fundamental neuroactive amino acid that serves dual roles in the central nervous system: acting as a primary inhibitory neurotransmitter via strychnine-sensitive glycine receptors and as an essential co-agonist at the N-methyl-D-aspartate (NMDA) receptor. This dual functionality is important for maintaining the excitation-inhibition balance, synaptic plasticity, and network stability. The spatial and temporal availability of glycine is strictly regulated by two high-affinity, Na/Cl-dependent transporters: GlyT1 (SLC6A9) and GlyT2 (SLC6A5). These transporters exhibit distinct cellular distributions and functional specializations. GlyT1 is predominantly expressed in astrocytes and specific neuronal populations, where it buffers ambient glycine levels to modulate NMDA receptor activity. In contrast, GlyT2 is primarily localized to presynaptic terminals of glycinergic neurons, where it facilitates vesicular refilling essential for inhibitory signaling. This review provides a comprehensive overview of glycine metabolism, the structural biology and transport cycles of SLC6 glycine transporters, and the neuroanatomical framework of GlyT1 function. We further synthesize pharmacological advances in GlyT1 inhibition, evaluating both sarcosine-derived and non-sarcosine inhibitors, such as NFPS (ALX-5407), bitopertin, and iclepertin. The clinical and preclinical evidence for GlyT1 as a therapeutic target in psychiatric, neurological, and neurodegenerative disorders is critically assessed. Finally, we address key translational challenges, including dosing constraints, compensatory mechanisms, and SLC6 family selectivity, while highlighting the potential of structure-guided design to refine GlyT1-targeted therapies. - Source: PubMed
Publication date: 2026/04/14
Cavalcante Daniel PereiraCarvalho Gustavo AlmeidaNunes Antônio Ítalo SantosQuintanilha Amanda RodriguesNascimento Lucas Rodrigues CoutoCaixeta LeonardoUlrich HenningGomez Renato SantiagoPinto Mauro Cunha Xavier - Meat quality characteristics are important economic traits of ducks. To identify the molecular bases of these traits, we performed an integrated multi-omics analysis (metabolomics, transcriptomics, and miRNAomics) that compared the breast muscle of 300-day-old Liancheng white duck (LD), which is a lean-type breed prized for its soup flavor, and traditional meat duck Cherry Valley duck (CD), which is a fast-growing fat-type breed used for roasting. The results show that LD had higher levels of amino and bile acids, while CD had higher levels of carbohydrates. Integration analysis revealed key breed-specific molecular signatures. In LD, upregulation of the amino acid transporters and related to amino acid transport was consistent with elevated intramuscular amino acids. For carbohydrate metabolism, -a well-established negative regulator of glucose uptake in mammalian skeletal muscle-was significantly upregulated in LD, consistent with their lower intramuscular carbohydrate levels. and were predicted to be negatively regulated by oan-miR-1386. In LD, upregulation of the bile acid biosynthesis gene paralleled the higher bile acid content, suggesting complex, tissue-specific regulation of these pathways. This integrated analysis provides a resource for candidate genes, miRNAs, and metabolic pathways underlying breed-specific meat quality traits in ducks. The findings generate testable hypotheses for future functional studies and offer potential molecular targets for breeding strategies aimed at improving poultry meat quality. - Source: PubMed
Publication date: 2026/03/16
Zhang LinliLiu XiaopanLi LiHuang LiangZhu ZhimingMiao ZhongweiZheng NenzhuXin Qingwu - The role of spindle and kinetochore-associated complex subunit 2 (SKA2) in gastric cancer (GC) pathogenesis remains largely undefined. Here, we report that SKA2 is overexpressed in GC and correlates with poor prognosis. Functionally, SKA2 silencing inhibits tumor growth, induces G2/M arrest, and promotes apoptosis both and . Mechanistically, SKA2 upregulates the glycine transporter SLC6A9, enhancing glycine uptake and glutathione (GSH) synthesis to maintain redox homeostasis. Consequently, SKA2 depletion disrupts this metabolic balance, leading to reactive oxygen species (ROS) accumulation and DNA damage. This oxidative stress activates the ATM/Chk2 pathway to trigger cell-cycle arrest and the ATM/JNK pathway to induce apoptosis. Our findings identify SKA2 as a critical driver of metabolic reprogramming that shields GC cells from oxidative stress-induced death, highlighting the SKA2-SLC6A9-GSH-ROS axis as a promising therapeutic target. - Source: PubMed
Publication date: 2026/03/03
Zhang PengZhong JianfengZhou TingJiang DepeiWang ZijingYe MeifangFang LekunXiong HuizhenChen Honglei - Intracerebral hemorrhage (ICH) is a common cerebrovascular disorder that frequently leads to white matter lesions (WML), resulting in persistent neurological deficits. However, the molecular mechanisms underlying ICH-induced WML remain incompletely understood. In this study, we employed an integrative bioinformatics approach combining two-trait Mendelian randomization (MR) analysis with single-cell RNA sequencing (scRNA-seq) to explore potential genetic contributors to WML following ICH. Based on expression quantitative trait loci (eQTL) data, MR analysis identified PRDX6 as a high-risk gene and SLC6A9 as a potential low-risk gene for WML following ICH. scRNA-seq further suggested cell-type-specific expression patterns of these genes in normal and ICH-affected mouse brain tissues. Functional enrichment analyses, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment, indicated that PRDX6 may be involved in antioxidant defense and metabolic processes, whereas SLC6A9 may be associated with transmembrane transport and neuroprotective functions. These findings offer new insights into the pathophysiology of ICH-induced WML and may serve as potential targets for future therapies. - Source: PubMed
Du WeiLong XiaoliLing ZefaPang KeXia XiaohuiYang Zhao