GlyT1 | Glycine transporter subfamily | IUPHAR/BPS Guide to PHARMACOLOGY

GlyT1

Target id: 935

Nomenclature: GlyT1

Systematic Nomenclature: SLC6A9

Family: Glycine transporter subfamily

Annotation status:  image of a grey circle Awaiting annotation/under development. Please contact us if you can help with annotation.  » Email us

   GtoImmuPdb view: OFF :     Currently no data for GlyT1 in GtoImmuPdb

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - - SLC6A9 solute carrier family 6 member 9
Mouse - - Slc6a9 solute carrier family 6 (neurotransmitter transporter, glycine), member 9
Rat - - Slc6a9 solute carrier family 6 member 9
Previous and Unofficial Names
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
Specialist databases
Bioparadigms SLC Tables SLC6A9 (Hs)
Other databases
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
UniProtKB
Wikipedia
Stoichiometry
2 Na+: 1 Cl-: 1 glycine

Download all structure-activity data for this target as a CSV file

Activators
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
GlyT1 inhibitor 51b Hs Inhibition 7.7 pKi 1
pKi 7.7 (Ki 1.8x10-8 M) [1]
Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
GlyT1 inhibitor 27a Hs Inhibition 9.1 pKi 1
pKi 9.1 (Ki 8x10-10 M) [1]
PF-03463275 Hs Inhibition 7.9 pKi 6
pKi 7.9 (Ki 1.16x10-8 M) [6]
bitopertin Hs Inhibition 7.3 pKi 1
pKi 7.3 (Ki 4.7x10-8 M) [1]
bitopertin Hs Inhibition 7.5 pEC50 7
pEC50 7.5 (EC50 3x10-8 M) [7]
SSR-103800 Hs Inhibition 8.7 pIC50 2
pIC50 8.7 (IC50 2x10-9 M) [2]
Other Binding Ligands
Key to terms and symbols Click column headers to sort
Ligand Sp. Action Affinity Units Reference
[3H](R)-NPTS Hs Binding 9.0 pKd 5
pKd 9.0 (Kd 1x10-9 M) [5]
[3H]GSK931145 Hs Binding 8.8 pKd 4
pKd 8.8 (Kd 1.7x10-9 M) [4]
[3H]SB-733993 Hs Binding 8.7 pKd 4
pKd 8.7 (Kd 2.2x10-9 M) [4]
[35S]ACPPB Hs Binding 8.7 pKd 8
pKd 8.7 (Kd 2x10-9 M) [8]
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) [3]. 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

Show »

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. 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]

4. 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]

5. 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]

6. 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]

7. 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]

8. 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

Show »

How to cite this page

Stefan Bröer.
Glycine transporter subfamily: GlyT1. Last modified on 28/08/2018. Accessed on 15/11/2018. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=935.