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GlyT1

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Target not currently curated in GtoImmuPdb

Target id: 935

Nomenclature: GlyT1

Systematic Nomenclature: SLC6A9

Family: Glycine transporter subfamily

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 12 706 1p34.1 SLC6A9 solute carrier family 6 member 9
Mouse 12 692 4 53.62 cM Slc6a9 solute carrier family 6 (neurotransmitter transporter, glycine), member 9
Rat 12 638 5q36 Slc6a9 solute carrier family 6 member 9
Previous and Unofficial Names Click here for help
Glycine transporter 1 | sodium- and chloride-dependent glycine transporter 1 | solute carrier family 6 member 9 | solute carrier family 6 (neurotransmitter transporter, glycine), member 9 | solute carrier family 6 (neurotransmitter transporter
Database Links Click here for help
Specialist databases
Bioparadigms SLC Tables SLC6A9 (Hs)
RESOLUTE SLC6A9 (Hs)
Other databases
Alphafold P48067 (Hs), P28571 (Mm), P28572 (Rn)
ChEMBL Target CHEMBL2337 (Hs), CHEMBL1075303 (Mm), CHEMBL4556 (Rn)
Ensembl Gene ENSG00000196517 (Hs), ENSMUSG00000028542 (Mm), ENSRNOG00000019484 (Rn)
Entrez Gene 6536 (Hs), 14664 (Mm), 116509 (Rn)
Human Protein Atlas ENSG00000196517 (Hs)
KEGG Gene hsa:6536 (Hs), mmu:14664 (Mm), rno:116509 (Rn)
OMIM 601019 (Hs)
Pharos P48067 (Hs)
UniProtKB P48067 (Hs), P28571 (Mm), P28572 (Rn)
Wikipedia SLC6A9 (Hs)
Stoichiometry Click here for help
2 Na+: 1 Cl-: 1 glycine

Download all structure-activity data for this target as a CSV file go icon to follow link

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
GlyT1 inhibitor 27a Small molecule or natural product Primary target of this compound Hs Inhibition 9.1 pKi 1
⤷ pKi 9.1 (Ki 8x10-10 M) [1]
PF-03463275 Small molecule or natural product Primary target of this compound Hs Inhibition 7.9 pKi 8
⤷ pKi 7.9 (Ki 1.16x10-8 M) [8]
GlyT1 inhibitor 51b Small molecule or natural product Primary target of this compound Hs Inhibition 7.7 pKi 1
⤷ pKi 7.7 (Ki 1.8x10-8 M) [1]
bitopertin Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.3 pKi 1
⤷ pKi 7.3 (Ki 4.7x10-8 M) [1]
bitopertin Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 7.5 pEC50 9
⤷ pEC50 7.5 (EC50 3x10-8 M) [9]
SSR-103800 Small molecule or natural product Hs Inhibition 8.7 pIC50 2
⤷ pIC50 8.7 (IC50 2x10-9 M) [2]
iclepertin Small molecule or natural product Hs Inhibition 8.3 pIC50 10
⤷ pIC50 8.3 (IC50 5x10-9 M) [10]
Description: Measuring inhibition of [3H]-glycine uptake in human SK-N-MC cells
iclepertin Small molecule or natural product Rn Inhibition 8.3 pIC50 10
⤷ pIC50 8.3 (IC50 5.2x10-9 M) [10]
Description: Inhibition of [3H]-glycine uptake in rat primary neurons
Org 24598 Small molecule or natural product Hs Inhibition 8.2 pIC50 3
⤷ pIC50 8.2 (IC50 6.3x10-9 M) [3]
Description: Inhibition of glycine uptake by hGlyT1b stably expressed in CHO cells.
ASP2535 Small molecule or natural product Rn Inhibition 7.0 pIC50 5
⤷ pIC50 7.0 (IC50 9.2x10-8 M) [5]
View species-specific inhibitor tables
Other Binding Ligands
Key to terms and symbols Click column headers to sort
Ligand Sp. Action Value Parameter Reference
[3H](R)-NPTS Small molecule or natural product Ligand is labelled Ligand is radioactive Hs Binding 9.0 pKd 7
⤷ pKd 9.0 (Kd 1x10-9 M) [7]
[3H]GSK931145 Small molecule or natural product Ligand is labelled Ligand is radioactive Hs Binding 8.8 pKd 6
⤷ pKd 8.8 (Kd 1.7x10-9 M) [6]
[3H]SB-733993 Small molecule or natural product Ligand is labelled Ligand is radioactive Hs Binding 8.7 pKd 6
⤷ pKd 8.7 (Kd 2.2x10-9 M) [6]
[35S]ACPPB Small molecule or natural product Ligand is labelled Ligand is radioactive Hs Binding 8.7 pKd 11
⤷ pKd 8.7 (Kd 2x10-9 M) [11]
General Comments
GlyT1 has ben localized to glutamatergic synapses where it forms a physical interaction with the NMDA receptor-associated scaffolding protein PSD-95 (DLG4; P78352) [4]. Because of its essential role in NMDA receptor function GlyT1 inhibition is being actively pursued as a novel pharmacological intervention for the treatment of schizophrenia, a disease that is associated with impaired (hypofunctional) NMDA-mediated neurotransmission.

References

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1. Amberg W, Lange UEW, Ochse M, Pohlki F, Behl B, Relo AL, Hornberger W, Hoft C, Mezler M, Sydor J et al.. (2018) Discovery of Novel Aminotetralines and Aminochromanes as Selective and Competitive Glycine Transporter 1 (GlyT1) Inhibitors. J Med Chem, 61 (17): 7503-7524. [PMID:30080045]

2. Boulay D, Pichat P, Dargazanli G, Estenne-Bouhtou G, Terranova JP, Rogacki N, Stemmelin J, Coste A, Lanneau C, Desvignes C et al.. (2008) Characterization of SSR103800, a selective inhibitor of the glycine transporter-1 in models predictive of therapeutic activity in schizophrenia. Pharmacol Biochem Behav, 91 (1): 47-58. [PMID:18621075]

3. Brown A, Carlyle I, Clark J, Hamilton W, Gibson S, McGarry G, McEachen S, Rae D, Thorn S, Walker G. (2001) Discovery and SAR of org 24598-a selective glycine uptake inhibitor. Bioorg Med Chem Lett, 11 (15): 2007-9. [PMID:11454468]

4. Cubelos B, González-González IM, Giménez C, Zafra F. (2005) The scaffolding protein PSD-95 interacts with the glycine transporter GLYT1 and impairs its internalization. J Neurochem, 95 (4): 1047-58. [PMID:16271045]

5. Harada K, Nakato K, Yarimizu J, Yamazaki M, Morita M, Takahashi S, Aota M, Saita K, Doihara H, Sato Y et al.. (2012) 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. Eur J Pharmacol, 685 (1-3): 59-69. [PMID:22542656]

6. Herdon HJ, Roberts JC, Coulton S, Porter RA. (2010) Pharmacological characterisation of the GlyT-1 glycine transporter using two novel radioligands. Neuropharmacology, 59 (6): 558-65. [PMID:20691713]

7. Lowe 3rd JA, Drozda SE, Fisher K, Strick C, Lebel L, Schmidt C, Hiller D, Zandi KS. (2003) [3H]-(R)-NPTS, a radioligand for the type 1 glycine transporter. Bioorg Med Chem Lett, 13 (7): 1291-2. [PMID:12657266]

8. Lowe 3rd JA, Hou X, Schmidt C, David Tingley 3rd F, McHardy S, Kalman M, Deninno S, Sanner M, Ward K, Lebel L et al.. (2009) The discovery of a structurally novel class of inhibitors of the type 1 glycine transporter. Bioorg Med Chem Lett, 19 (11): 2974-6. [PMID:19410451]

9. Pinard E, Alanine A, Alberati D, Bender M, Borroni E, Bourdeaux P, Brom V, Burner S, Fischer H, Hainzl D et al.. (2010) 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. [PMID:20491477]

10. Rosenbrock H, Desch M, Kleiner O, Dorner-Ciossek C, Schmid B, Keller S, Schlecker C, Moschetti V, Goetz S, Liesenfeld KH et al.. (2018) Evaluation of Pharmacokinetics and Pharmacodynamics of BI 425809, a Novel GlyT1 Inhibitor: Translational Studies. Clin Transl Sci, 11 (6): 616-623. [PMID:30136756]

11. Zeng Z, O'Brien JA, Lemaire W, O'Malley SS, Miller PJ, Zhao Z, Wallace MA, Raab C, Lindsley CW, Sur C et al.. (2008) A novel radioligand for glycine transporter 1: characterization and use in autoradiographic and in vivo brain occupancy studies. Nucl Med Biol, 35 (3): 315-25. [PMID:18355687]

Contributors

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