Target Information

Target General Infomation
Target ID
T69685
Former ID
TTDC00227
Target Name
Sodium- and chloride-dependent glycine transporter 1
Gene Name
SLC6A9
Synonyms
GlyT-1; GlyT1; Glycine transporter type 1; Glycine type-1 transporter; SLC6A9
Target Type
Clinical Trial
Disease Dementia [ICD9: 290-294; ICD10: F01-F07]
Psychotic disorders [ICD9: 290-299; ICD10: F20-F29]
Schizophrenia [ICD9: 295; ICD10: F20]
Function
Terminates the action of glycine by its high affinity sodium-dependent reuptake into presynaptic terminals. May play a role in regulation of glycine levels in NMDA receptor-mediated neurotransmission.
BioChemical Class
Neurotransmitter:sodium symporter
Target Validation
T69685
UniProt ID
P48067
Sequence
MSGGDTRAAIARPRMAAAHGPVAPSSPEQVTLLPVQRSFFLPPFSGATPSTSLAESVLKV
WHGAYNSGLLPQLMAQHSLAMAQNGAVPSEATKRDQNLKRGNWGNQIEFVLTSVGYAVGL
GNVWRFPYLCYRNGGGAFMFPYFIMLIFCGIPLFFMELSFGQFASQGCLGVWRISPMFKG
VGYGMMVVSTYIGIYYNVVICIAFYYFFSSMTHVLPWAYCNNPWNTHDCAGVLDASNLTN
GSRPAALPSNLSHLLNHSLQRTSPSEEYWRLYVLKLSDDIGNFGEVRLPLLGCLGVSWLV
VFLCLIRGVKSSGKVVYFTATFPYVVLTILFVRGVTLEGAFDGIMYYLTPQWDKILEAKV
WGDAASQIFYSLGCAWGGLITMASYNKFHNNCYRDSVIISITNCATSVYAGFVIFSILGF
MANHLGVDVSRVADHGPGLAFVAYPEALTLLPISPLWSLLFFFMLILLGLGTQFCLLETL
VTAIVDEVGNEWILQKKTYVTLGVAVAGFLLGIPLTSQAGIYWLLLMDNYAASFSLVVIS
CIMCVAIMYIYGHRNYFQDIQMMLGFPPPLFFQICWRFVSPAIIFFILVFTVIQYQPITY
NHYQYPGWAVAIGFLMALSSVLCIPLYAMFRLCRTDGDTLLQRLKNATKPSRDWGPALLE
HRTGRYAPTIAPSPEDGFEVQPLHPDKAQIPIVGSNGSSRLQDSRI
Drugs and Mode of Action
Drug(s) R1678 Drug Info Phase 3 Schizophrenia [523242], [542547]
AMG 747 Drug Info Phase 2 Schizophrenia [523858]
ORG-25935 Drug Info Phase 2 Psychotic disorders [522391]
PF-3463275 Drug Info Phase 2 Schizophrenia [522783]
ALX-5407 Drug Info Phase 1 Schizophrenia [467857], [536463]
DCCCyB Drug Info Phase 1 Schizophrenia [548843]
GlyT1 PET radiotracers Drug Info Phase 1 Schizophrenia [532944]
JNJ-17305600 Drug Info Phase 1 Schizophrenia [548551]
MK-2637 Drug Info Phase 1 Schizophrenia [522716]
Org-24461 Drug Info Preclinical Schizophrenia [536463]
Organon Drug Info Preclinical Schizophrenia [533495]
Organon-2 Drug Info Preclinical Schizophrenia [536463]
Organon-3 Drug Info Preclinical Schizophrenia [536463]
SSR-103800 Drug Info Preclinical Schizophrenia [468008], [536463]
SSR-504734 Drug Info Preclinical Schizophrenia [536463]
GSK1018921 Drug Info Discontinued in Phase 1 Schizophrenia [548688]
Blocker ALX-5407 Drug Info [526208], [536463]
GSK1018921 Drug Info [550963]
NFPS Drug Info [535780]
Org-24461 Drug Info [536463]
Organon Drug Info [536463]
Organon-2 Drug Info [536463]
Organon-3 Drug Info [536463]
R1678 Drug Info [551607]
SSR-103800 Drug Info [536463]
SSR-504734 Drug Info [536463]
Modulator AMG 747 Drug Info [532527]
DCCCyB Drug Info [544400]
GlyT1 PET radiotracers Drug Info [544160]
MK-2637 Drug Info [532944]
[35S]ACPPB Drug Info [529382]
[3H](R)-NPTS Drug Info [526583]
[3H]GSK931145 Drug Info [531091]
[3H]N-methyl-SSR504734 Drug Info [543979]
[3H]NFPS Drug Info [543979]
[3H]SB-733993 Drug Info [531091]
Inhibitor AS-1522489-00 Drug Info [543979]
Glycine type-1 transporter inhibitors Drug Info [543979]
GSK931145 Drug Info [543979]
JNJ-17305600 Drug Info [543979]
LY2365109 Drug Info [543979]
N-methyl-SSR504734 Drug Info [543979]
ORG-25935 Drug Info [532527], [532672]
PF-3463275 Drug Info [532527]
RO-4840700 Drug Info [543979]
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM)
TEP EXP Info
Pathways
Reactome Na+/Cl- dependent neurotransmitter transporters
WikiPathways NRF2 pathway
References
Ref 467857(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 4618).
Ref 468008(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 4778).
Ref 522391ClinicalTrials.gov (NCT00725725) Org 25935 Versus Placebo as Augmentation to Cognitive-behavioral Therapy to Treat Panic Disorder (P05705AM3)(TERMINATED). U.S. National Institutes of Health.
Ref 522716ClinicalTrials.gov (NCT00934466) Study of the Effect of Single Doses of MK2637 and Dextromethorphan on Cerebral Cortex Excitability (2637-008). U.S. National Institutes of Health.
Ref 522783ClinicalTrials.gov (NCT00977522) A Study Of PF-03463275 As Add-On Therapy In Outpatients With Persistent Negative Symptoms Of Schizophrenia. U.S. National Institutes of Health.
Ref 523242ClinicalTrials.gov (NCT01235559) A Study of RO4917838 (Bitopertin) in Patients With Sub-optimally Controlled Symptoms of Schizophrenia (WN25305). U.S. National Institutes of Health.
Ref 523858ClinicalTrials.gov (NCT01568216) 20101299: Study to Evaluate the Effect of AMG 747 on Schizophrenia Negative Symptoms. U.S. National Institutes of Health.
Ref 532944Characterization of the novel GlyT1 PET tracer [18F]MK-6577 in humans. Synapse. 2015 Jan;69(1):33-40.
Ref 533495Receptor binding of allylestrenol, a progestagen of the 19-nortestosterone series without androgenic properties. J Steroid Biochem. 1985 Aug;23(2):165-8.
Ref 536463The pipeline and future of drug development in schizophrenia. Mol Psychiatry. 2007 Oct;12(10):904-22. Epub 2007 Jul 31.
Ref 542547(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7546).
Ref 548551Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800026554)
Ref 548688Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800027678)
Ref 548843Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800029447)
Ref 526208Mol Pharmacol. 2001 Dec;60(6):1414-20.ALX 5407: a potent, selective inhibitor of the hGlyT1 glycine transporter.
Ref 526583[3H]-(R)-NPTS, a radioligand for the type 1 glycine transporter. Bioorg Med Chem Lett. 2003 Apr 7;13(7):1291-2.
Ref 529382A novel radioligand for glycine transporter 1: characterization and use in autoradiographic and in vivo brain occupancy studies. Nucl Med Biol. 2008 Apr;35(3):315-25.
Ref 531091Pharmacological characterisation of the GlyT-1 glycine transporter using two novel radioligands. Neuropharmacology. 2010 Nov;59(6):558-65.
Ref 532527Glycine transporters as novel therapeutic targets in schizophrenia, alcohol dependence and pain. Nat Rev Drug Discov. 2013 Nov;12(11):866-85.
Ref 532672The selective glycine uptake inhibitor org 25935 as an adjunctive treatment to atypical antipsychotics in predominant persistent negative symptoms of schizophrenia: results from the GIANT trial. J Clin Psychopharmacol. 2014 Apr;34(2):190-8.
Ref 532944Characterization of the novel GlyT1 PET tracer [18F]MK-6577 in humans. Synapse. 2015 Jan;69(1):33-40.
Ref 535780The glycine transporter type 1 inhibitor N-[3-(4'-fluorophenyl)-3-(4'-phenylphenoxy)propyl]sarcosine potentiates NMDA receptor-mediated responses in vivo and produces an antipsychotic profile in rodent behavior. J Neurosci. 2003 Aug 20;23(20):7586-91.
Ref 536463The pipeline and future of drug development in schizophrenia. Mol Psychiatry. 2007 Oct;12(10):904-22. Epub 2007 Jul 31.
Ref 543979(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 935).
Ref 544160Glycine Transport Inhibitors for the Treatment of Schizophrenia. Open Med Chem J. 2010; 4: 10-19.
Ref 544400Identification of an Orally Bioavailable, Potent, and Selective Inhibitor of GlyT1. ACS Med Chem Lett. 2010 October 14; 1(7): 350-354.
Ref 550963Clinical pipeline report, company report or official report of GlaxoSmithKline (2009).
Ref 551607Clinical pipeline report, company report or official report of Roche (2009).

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