Biology:Sodium- and chloride-dependent glycine transporter 1
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Short description: Protein-coding gene in the species Homo sapiens
 Generic protein structure example |
Sodium- and chloride-dependent glycine transporter 1, also known as glycine transporter 1, is a protein that in humans is encoded by the SLC6A9 gene which is promising therapeutic target for treatment of diabetes and obesity. [1][2][3][4]
Selective inhibitors
Elevation of extracellular synaptic glycine concentration by blockade of GlyT1 has been hypothesized to potentiate NMDA receptor function in vivo and to represent a rational approach for the treatment of schizophrenia and cognitive disorders. Several drug candidates have reached clinical trials.[5]
- ASP2535[6]
- Bitopertin (RG1678), which has entered phase II trials for the treatment of schizophrenia[7]
- Iclepertin (BI 425809) by Boehringer Ingelheim which is thought to improve cognitive impairment due to schizophrenia
- Org 25935 (Sch 900435)
- PF-03463275 (in phase II trial)
- Pesampator (PF-04958242) by Pfizer
- Sarcosine which is thought to improve cognitive impairment due to schizophrenia
Pathological mutations
Mutations of the gene may cause a severe metabolic disorder discovered in 2016 and called glycine encephalopathy with normal serum glycine (OMIM 617301), also known as GlyT1 encephalopathy.
See also
- Sodium:neurotransmitter symporter
- Solute carrier family
References
- ↑ Sinha, Jitendra Kumar; Durgvanshi, Shantanu; Verma, Manish; Ghosh, Shampa (June 2023). "Investigation of SLC6A9 and SLC5A1 as a promising therapeutic target for obesity and diabetes using in silico characterization, 3D structure prediction and molecular docking analysis" (in en). Alzheimer's & Dementia 19 (S1). doi:10.1002/alz.064229. ISSN 1552-5260.
- ↑ "Cloning of the human glycine transporter type 1: molecular and pharmacological characterization of novel isoform variants and chromosomal localization of the gene in the human and mouse genomes". Mol Pharmacol 45 (4): 608–17. Jun 1994. PMID 8183239.
- ↑ "Assignment of SLC6A9 to human chromosome band 1p33 by in situ hybridization". Cytogenet Cell Genet 71 (3): 211. Nov 1995. doi:10.1159/000134110. PMID 7587377.
- ↑ "Entrez Gene: SLC6A9 solute carrier family 6 (neurotransmitter transporter, glycine), member 9". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=6536.
- ↑ Harvey, Robert J.; Yee, Benjamin K. (31 October 2013). "Glycine transporters as novel therapeutic targets in schizophrenia, alcohol dependence and pain". Nature Reviews Drug Discovery 12 (11): 866–85. doi:10.1038/nrd3893. PMID 24172334.
- ↑ "A novel glycine transporter-1 (GlyT1) inhibitor, ASP2535 (4-[3-isopropyl-5-(6-phenyl-3-pyridyl)-4H-1,2,4-triazol-4-yl]-2,1,3-benzoxadiazole), improves cognition in animal models of cognitive impairment in schizophrenia and Alzheimer's disease". European Journal of Pharmacology 685 (1–3): 59–69. 2012. doi:10.1016/j.ejphar.2012.04.013. PMID 22542656.
- ↑ "Selective GlyT1 inhibitors: discovery of [4-(3-fluoro-5-trifluoromethylpyridin-2-yl)piperazin-1-yl][5-methanesulfonyl-2-((S)-2,2,2-trifluoro-1-methylethoxy)phenyl]methanone (RG1678), a promising novel medicine to treat schizophrenia". J. Med. Chem. 53 (12): 4603–14. June 2010. doi:10.1021/jm100210p. PMID 20491477.
Further reading
- "The role of N-glycosylation in the targeting and activity of the GLYT1 glycine transporter". J. Biol. Chem. 270 (16): 9437–42. 1995. doi:10.1074/jbc.270.16.9437. PMID 7721869.
- "Two glycine transporter variants with distinct localization in the CNS and peripheral tissues are encoded by a common gene". Neuron 10 (5): 851–63. 1993. doi:10.1016/0896-6273(93)90201-2. PMID 8494645.
- "Cloning, functional characterisation and population analysis of a variant form of the human glycine type 2 transporter". FEBS Lett. 463 (3): 301–6. 2000. doi:10.1016/S0014-5793(99)01636-1. PMID 10606742.
- "GABA receptor rho1 subunit interacts with a novel splice variant of the glycine transporter, GLYT-1". J. Biol. Chem. 275 (2): 840–6. 2000. doi:10.1074/jbc.275.2.840. PMID 10625616.
- "Characterization of the interactions between the glycine transporters GLYT1 and GLYT2 and the SNARE protein syntaxin 1A". FEBS Lett. 470 (1): 51–4. 2000. doi:10.1016/S0014-5793(00)01297-7. PMID 10722844.
- "Glycine supply to human enterocytes mediated by high-affinity basolateral GLYT1". Gastroenterology 120 (2): 439–48. 2001. doi:10.1053/gast.2001.21207. PMID 11159884.
- "Glyt-1 expression in cultured human Müller cells and intact retinae". Glia 34 (4): 311–5. 2001. doi:10.1002/glia.1064. PMID 11360303.
- "Glycine transporter isoforms show differential subcellular localization in PC12 cells". J. Neurochem. 82 (1): 58–65. 2002. doi:10.1046/j.1471-4159.2002.00930.x. PMID 12091465.
- "Transcriptome characterization elucidates signaling networks that control human ES cell growth and differentiation". Nat. Biotechnol. 22 (6): 707–16. 2005. doi:10.1038/nbt971. PMID 15146197.
- "The mechanism of allosteric interaction of cytoplasmic and extracellular Cl− in the glial glycine transporter (hGlyTlb)". Dokl. Biol. Sci. 402 (1–6): 163–6. 2005. doi:10.1007/s10630-005-0076-z. PMID 16121932.
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