Details of the Drug Transporter (DTP)

General Information of Drug Transporter (DTP) (ID: DT2CFQ5)

DTP Name Sodium- and chloride-dependent glycine transporter 1 (SLC6A9)
Gene Name SLC6A9
UniProt ID
P48067 (SC6A9_HUMAN)
VARIDT ID
DTD0461
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Synonyms GCENSG; GlyT-1; GlyT1; SLC6A9; Solute carrier family 6 member 9
DTP Family Neurotransmitter:Sodium Symporter (NSS) Family ;
Tissue Specificity Isoform GlyT-1A and isoform GlyT-1B can befound in brain, kidney, pancreas, lung, placenta and liver butisoform GlyT-1C is only found in brain.
Sequence
MSGGDTRAAIARPRMAAAHGPVAPSSPEQVTLLPVQRSFFLPPFSGATPSTSLAESVLKV
WHGAYNSGLLPQLMAQHSLAMAQNGAVPSEATKRDQNLKRGNWGNQIEFVLTSVGYAVGL
GNVWRFPYLCYRNGGGAFMFPYFIMLIFCGIPLFFMELSFGQFASQGCLGVWRISPMFKG
VGYGMMVVSTYIGIYYNVVICIAFYYFFSSMTHVLPWAYCNNPWNTHDCAGVLDASNLTN
GSRPAALPSNLSHLLNHSLQRTSPSEEYWRLYVLKLSDDIGNFGEVRLPLLGCLGVSWLV
VFLCLIRGVKSSGKVVYFTATFPYVVLTILFVRGVTLEGAFDGIMYYLTPQWDKILEAKV
WGDAASQIFYSLGCAWGGLITMASYNKFHNNCYRDSVIISITNCATSVYAGFVIFSILGF
MANHLGVDVSRVADHGPGLAFVAYPEALTLLPISPLWSLLFFFMLILLGLGTQFCLLETL
VTAIVDEVGNEWILQKKTYVTLGVAVAGFLLGIPLTSQAGIYWLLLMDNYAASFSLVVIS
CIMCVAIMYIYGHRNYFQDIQMMLGFPPPLFFQICWRFVSPAIIFFILVFTVIQYQPITY
NHYQYPGWAVAIGFLMALSSVLCIPLYAMFRLCRTDGDTLLQRLKNATKPSRDWGPALLE
HRTGRYAPTIAPSPEDGFEVQPLHPDKAQIPIVGSNGSSRLQDSRI
Function
This transporter can terminate the action of glycine by its high affinity sodium-dependent reuptake into presynaptic terminals and may play a role in regulation of glycine levels in NMDA receptor-mediated neurotransmission.
Endogenous Substrate(s) Cl-; Na+
TCDB ID
2.A.22.2.12
Gene ID
6536
KEGG Pathway
Synaptic vesicle cycle (hsa04721 )
Reactome Pathway
Na+/Cl- dependent neurotransmitter transporters (R-HSA-442660 )

Molecular Interaction Atlas (MIA) of This DTP

Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DTP
1 Approved Drug(s) Transported by This DTP
Drug Name Drug ID Indication ICD 11 Highest Status REF
Glycine DMIOZ29 Allergic rhinitis CA08.0 Approved [17]
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1 Investigative Drug(s) Transported by This DTP
Drug Name Drug ID Indication ICD 11 Highest Status REF
sarcosine DMIVGOR Discovery agent N.A. Investigative [18]
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Molecular Expression Atlas (MEA) of This DTP

Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This DTP
Disease Name ICD 11 Studied Tissue p-value Fold-Change Z-score
Acute myelocytic leukaemia 2B33.1 Bone marrow 2.04E-03 -3.08E-01 -6.05E-01
Adrenocortical carcinoma 2D11.Z Kidney 1.87E-01 -5.43E-01 -6.12E-01
Alopecia ED70 Skin from scalp 3.80E-01 6.46E-02 2.00E-01
Alzheimer's disease 8A20 Entorhinal cortex 2.47E-03 2.14E-01 3.94E-01
Ankylosing spondylitis FA92.0 Pheripheral blood 7.91E-01 2.32E-02 2.31E-01
Aortic stenosis BB70 Calcified aortic valve 7.75E-01 3.16E-01 6.45E-01
Apnea 7A40 Hyperplastic tonsil 1.75E-01 -3.69E-01 -1.34E+00
Arthropathy FA00-FA5Z Peripheral blood 7.88E-01 7.11E-02 2.23E-01
Asthma CA23 Nasal and bronchial airway 1.72E-06 -2.30E-01 -1.50E-01
Atopic dermatitis EA80 Skin 3.87E-02 -4.61E-01 -6.97E-01
Autism 6A02 Whole blood 8.15E-03 -2.11E-01 -8.01E-01
Autoimmune uveitis 9A96 Peripheral monocyte 5.68E-02 -7.06E-02 -3.31E-01
Autosomal dominant monocytopenia 4B04 Whole blood 8.59E-01 2.91E-02 2.45E-01
Bacterial infection of gingival 1C1H Gingival tissue 3.56E-01 -1.24E-01 -1.66E-01
Batten disease 5C56.1 Whole blood 9.28E-01 8.91E-03 6.77E-02
Behcet's disease 4A62 Peripheral blood 2.83E-01 0.00E+00 0.00E+00
Bipolar disorder 6A60-6A6Z Prefrontal cortex 1.16E-01 -5.14E-02 -3.41E-01
Bladder cancer 2C94 Bladder tissue 6.73E-01 -9.18E-02 -1.53E-01
Breast cancer 2C60-2C6Z Breast tissue 8.86E-09 6.20E-02 1.58E-01
Cardioembolic stroke 8B11.20 Whole blood 9.81E-02 2.08E-01 4.18E-01
Cervical cancer 2C77 Cervical tissue 1.51E-03 1.21E-01 5.05E-01
Childhood onset rheumatic disease FA20.Z Peripheral blood 8.58E-01 3.15E-02 1.10E-01
Chronic hepatitis C 1E51.1 Whole blood 1.38E-01 7.86E-03 3.89E-02
Chronic obstructive pulmonary disease CA22 Lung tissue 7.97E-01 2.50E-02 8.93E-02
Chronic obstructive pulmonary disease CA22 Small airway epithelium 8.56E-01 -4.71E-03 -6.86E-03
Chronic rhinosinusitis CA0A Sinus mucosa tissue 9.51E-01 9.49E-02 3.10E-01
Colon cancer 2B90 Colon tissue 1.25E-35 -6.98E-01 -1.27E+00
Coronary artery disease BA80-BA8Z Peripheral blood 2.38E-02 -3.17E-01 -2.27E+00
Diffuse large B-cell lymphoma 2A81 Tonsil tissue 5.81E-01 -1.23E-01 -3.91E-01
Endometriosis GA10 Endometrium tissue 3.95E-01 -1.07E-01 -3.65E-01
Familial hypercholesterolemia 5C80.00 Peripheral blood 8.46E-01 -8.47E-02 -3.98E-01
Familial hypercholesterolemia 5C80.00 Whole blood 1.43E-04 -6.44E-01 -1.52E+00
Gastric cancer 2B72 Gastric tissue 9.71E-01 -1.07E-01 -6.25E-01
Glioblastopma 2A00.00 Nervous tissue 1.37E-01 -3.52E-01 -5.48E-01
Glioma 2A00.0Y-2A00.0Z White matter tissue 2.45E-03 -3.13E-01 -1.01E+00
Head and neck cancer 2D42 Head and neck tissue 1.92E-04 -2.35E-01 -5.16E-01
HIV-associated neurocognitive impairment 8A2Y-8A2Z White matter tissue 6.26E-01 -6.34E-02 -2.37E-01
Huntington's disease 8A01.10 Whole blood 7.35E-01 -4.47E-02 -3.44E-01
Idiopathic pulmonary fibrosis CB03.4 Lung tissue 3.55E-01 -2.04E-01 -7.09E-01
Immunodeficiency 4A00-4A20 Peripheral blood 8.96E-01 -1.05E-02 -9.02E-02
Influenza 1.00E+30 Whole blood 6.57E-02 2.40E-01 2.01E+00
Interstitial cystitis GC00.3 Bladder tissue 7.14E-01 2.29E-02 7.22E-02
Intracranial aneurysm 8B01.0 Intracranial artery 7.74E-01 -3.56E-02 -1.52E-01
Irritable bowel syndrome DD91.0 Rectal colon tissue 8.49E-01 5.91E-03 2.33E-02
Ischemic stroke 8B11 Peripheral blood 6.11E-01 1.93E-02 1.05E-01
Juvenile idiopathic arthritis FA24 Peripheral blood 4.49E-03 6.50E-02 2.15E-01
Lateral sclerosis 8B60.4 Cervical spinal cord 2.73E-01 4.17E-02 2.31E-01
Lateral sclerosis 8B60.4 Skin 5.87E-01 -1.88E-01 -4.52E-01
Liver cancer 2C12.0 Liver tissue 5.40E-01 -6.28E-02 -2.12E-01
Liver failure DB99.7-DB99.8 Liver tissue 9.59E-01 -3.71E-02 -1.67E-01
Lung cancer 2C25 Lung tissue 5.38E-15 -3.12E-01 -7.08E-01
Lupus erythematosus 4A40 Whole blood 2.21E-03 -2.42E-01 -5.21E-01
Major depressive disorder 6A70-6A7Z Whole blood 1.82E-01 2.02E-02 8.65E-02
Major depressive disorder 6A70-6A7Z Hippocampus 3.93E-01 -2.12E-02 -1.42E-01
Melanoma 2C30 Skin 3.75E-01 -2.38E-01 -2.65E-01
Multiple myeloma 2A83.1 Bone marrow 9.65E-03 5.02E-02 3.40E-01
Multiple myeloma 2A83.1 Peripheral blood 7.86E-01 6.00E-02 3.27E-01
Multiple sclerosis 8A40 Plasmacytoid dendritic cells 2.47E-01 2.64E-01 5.81E-01
Myelodysplastic syndrome 2A36-2A3Z Bone marrow 9.23E-01 -5.55E-02 -2.44E-01
Myelofibrosis 2A20.2 Whole blood 3.93E-02 1.23E-01 6.25E-01
Myocardial infarction BA41-BA50 Peripheral blood 2.00E-03 3.98E-01 8.45E-01
Myopathy 8C70.6 Muscle tissue 9.21E-01 6.52E-02 6.25E-01
Neonatal sepsis KA60 Whole blood 2.47E-01 -6.55E-02 -1.85E-01
Neuroectodermal tumour 2A00.11 Brain stem tissue 1.36E-06 -1.72E+00 -3.62E+00
Non-alcoholic fatty liver disease DB92 Liver tissue 6.36E-01 -1.17E-01 -4.80E-01
Obesity related type 2 diabetes 5A11 Omental adipose tissue 4.23E-01 3.38E-02 1.91E-01
Olive pollen allergy CA08.00 Peripheral blood 4.70E-01 2.29E-01 6.80E-01
Oral cancer 2B6E Oral tissue 2.20E-03 -3.53E-01 -6.03E-01
Osteoarthritis FA00-FA0Z Synovial tissue 6.92E-01 -1.97E-01 -9.02E-01
Osteoporosis FB83.1 Bone marrow 1.64E-02 5.73E-01 1.81E+00
Ovarian cancer 2C73 Ovarian tissue 2.17E-01 1.77E-01 4.52E-01
Pancreatic cancer 2C10 Pancreas 7.99E-01 -1.85E-03 -6.41E-03
Parkinson's disease 8A00.0 Substantia nigra tissue 6.10E-01 -3.57E-01 -8.09E-01
Pediatric respiratory syncytial virus infection CA40.11 Peripheral blood 2.89E-01 5.27E-02 3.70E-01
Pituitary cancer 2D12 Pituitary tissue 8.88E-02 1.03E-01 3.63E-01
Pituitary gonadotrope tumour 2D12 Pituitary tissue 1.05E-01 1.45E-01 4.05E-01
Polycystic ovary syndrome 5A80.1 Vastus lateralis muscle 5.03E-02 1.06E-01 8.22E-01
Polycythemia vera 2A20.4 Whole blood 1.52E-05 2.22E-01 1.12E+00
Pompe disease 5C51.3 Biceps muscle 5.14E-01 -3.64E-02 -2.66E-01
Preterm birth KA21.4Z Myometrium 4.87E-01 -7.31E-02 -3.68E-01
Prostate cancer 2C82 Prostate 8.29E-01 -4.20E-02 -1.15E-01
Psoriasis EA90 Skin 1.04E-01 -4.45E-01 -5.06E-01
Rectal cancer 2B92 Rectal colon tissue 7.39E-04 -4.62E-01 -2.19E+00
Renal cancer 2C90-2C91 Kidney 2.47E-01 2.31E-02 8.41E-02
Retinoblastoma 2D02.2 Uvea 3.72E-07 -1.48E+00 -2.77E+00
Rheumatoid arthritis FA20 Synovial tissue 7.40E-01 1.39E-01 3.76E-01
Rhinovirus infection CA42.1 Nasal epithelium tissue 4.76E-01 2.30E-02 8.47E-02
Schizophrenia 6A20 Prefrontal cortex 4.94E-01 -8.60E-02 -3.42E-01
Schizophrenia 6A20 Superior temporal cortex 1.64E-01 -3.45E-02 -1.71E-01
Scleroderma 4A42.Z Whole blood 3.99E-01 6.88E-03 3.83E-02
Seizure 8A60-8A6Z Whole blood 2.71E-01 -1.09E-01 -2.74E-01
Sensitive skin EK0Z Skin 2.14E-01 2.19E-01 5.08E-01
Sepsis with septic shock 1G41 Whole blood 3.19E-01 1.02E-01 3.03E-01
Shwachman-Diamond syndrome 3A70.0 Bone marrow 1.17E-02 4.31E-01 1.00E+00
Sickle cell disease 3A51.0-3A51.3 Peripheral blood 8.11E-01 2.80E-02 1.49E-01
Simpson golabi behmel syndrome LD2C Adipose tissue 6.29E-01 -1.45E-02 -8.10E-02
Sjogren's syndrome 4A43.2 Salivary gland tissue 4.54E-01 -6.80E-02 -1.06E+00
Skin cancer 2C30-2C3Z Skin 9.75E-27 -1.45E+00 -1.71E+00
Thrombocythemia 3B63 Whole blood 5.70E-02 1.75E-01 8.85E-01
Thrombocytopenia 3B64 Whole blood 7.54E-01 1.52E-02 9.04E-02
Thyroid cancer 2D10 Thyroid 1.63E-01 -6.58E-02 -2.24E-01
Tibial muscular dystrophy 8C75 Muscle tissue 2.48E-04 -2.03E-01 -8.82E-01
Tuberous sclerosis complex LD2D.2 Perituberal tissue 1.32E-01 1.76E-01 1.40E+00
Type 2 diabetes 5A11 Liver tissue 6.18E-01 -5.06E-02 -5.40E-01
Ureter cancer 2C92 Urothelium 5.87E-01 5.92E-02 4.11E-01
Uterine cancer 2C78 Endometrium tissue 1.73E-06 9.70E-02 3.26E-01
Vitiligo ED63.0 Skin 6.17E-04 3.55E-01 2.56E+00
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⏷ Show the Full List of Expression Under 107 Diseases

The Drug Therapeutic Target (DTT) Role of This DTP

DTP DTT Name Glycine transporter GlyT-1 (SLC6A9) DTT Info
DTP DTT Type Clinical trial
11 Clinical Trial Drug(s) Targeting This DTP
Drug Name Drug ID Indication ICD 11 Highest Status REF
BI 425809 DMH3XDR Schizophrenia 6A20 Phase 3 [1]
Iclepertin DM83JCK Schizophrenia 6A20 Phase 3 [2]
R1678 DM4K9WH Schizophrenia 6A20 Phase 3 [3]
AMG 747 DMWPGB8 Schizophrenia 6A20 Phase 2 [4]
ORG-25935 DMWN2EC Psychotic disorder 6A20-6A25 Phase 2 [5]
PF-3463275 DMO02LU Schizophrenia 6A20 Phase 2 [4]
ALX-5407 DMLJWPN Schizophrenia 6A20 Phase 1 [6]
DCCCyB DMQ8ACY Schizophrenia 6A20 Phase 1 [7]
GlyT1 PET radiotracers DMCKZUT Schizophrenia 6A20 Phase 1 [8]
JNJ-17305600 DMMI4XR Schizophrenia 6A20 Phase 1 [9]
MK-2637 DMUHOJP Schizophrenia 6A20 Phase 1 [10]
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⏷ Show the Full List of 11 Clinical Trial Drug(s)
33 Patented Agent(s) Targeting This DTP
Drug Name Drug ID Indication ICD 11 Highest Status REF
PMID29338548-Compound-13 DMDJFUX Schizophrenia 6A20 Patented [11]
PMID29338548-Compound-14 DMXIO9A N. A. N. A. Patented [11]
PMID29338548-Compound-15 DM6J0Z8 N. A. N. A. Patented [11]
PMID29338548-Compound-16 DMQNVUB N. A. N. A. Patented [11]
PMID29338548-Compound-17 DMFXCPQ N. A. N. A. Patented [11]
PMID29338548-Compound-18 DM0XA3D N. A. N. A. Patented [11]
PMID29338548-Compound-19 DMKHTE1 N. A. N. A. Patented [11]
PMID29338548-Compound-20 DMZ3EHV N. A. N. A. Patented [11]
PMID29338548-Compound-21 DMRTBKC Schizophrenia 6A20 Patented [11]
PMID29338548-Compound-22 DMT3AL5 N. A. N. A. Patented [11]
PMID29338548-Compound-23 DMTA3D8 N. A. N. A. Patented [11]
PMID29338548-Compound-24 DMWRGOX N. A. N. A. Patented [11]
PMID29338548-Compound-25 DM83LWC N. A. N. A. Patented [11]
PMID29338548-Compound-26 DMT2D5H N. A. N. A. Patented [11]
PMID29338548-Compound-27 DMNW37Y N. A. N. A. Patented [11]
PMID29338548-Compound-28 DMNBT3K N. A. N. A. Patented [11]
PMID29338548-Compound-29 DMUGC53 N. A. N. A. Patented [11]
PMID29338548-Compound-30 DM8JK2D N. A. N. A. Patented [11]
PMID29338548-Compound-31 DMWMPE2 N. A. N. A. Patented [11]
PMID29338548-Compound-33 DM4Q5SW N. A. N. A. Patented [11]
PMID29338548-Compound-34 DM839NQ N. A. N. A. Patented [11]
PMID29338548-Compound-36 DMG675B N. A. N. A. Patented [11]
PMID29338548-Compound-37 DMAM0US N. A. N. A. Patented [11]
PMID29338548-Compound-38 DM6BKQ8 N. A. N. A. Patented [11]
PMID29338548-Compound-39 DM69Y7R N. A. N. A. Patented [11]
PMID29338548-Compound-40 DMLAHC1 N. A. N. A. Patented [11]
PMID29338548-Compound-41 DM2L7ES N. A. N. A. Patented [11]
PMID29338548-Compound-44 DMJYQLC N. A. N. A. Patented [11]
PMID29338548-Compound-45 DMO4JYK N. A. N. A. Patented [11]
PMID29338548-Compound-46 DMRKIA1 N. A. N. A. Patented [11]
PMID29338548-Compound-47 DMHBOK6 N. A. N. A. Patented [11]
PMID29338548-Compound-48 DMDRJHO N. A. N. A. Patented [11]
PMID29338548-Compound-49 DM1NJ3U N. A. N. A. Patented [11]
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⏷ Show the Full List of 33 Patented Agent(s)
1 Discontinued Drug(s) Targeting This DTP
Drug Name Drug ID Indication ICD 11 Highest Status REF
GSK1018921 DM7ACJ4 Schizophrenia 6A20 Discontinued in Phase 1 [12]
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6 Preclinical Drug(s) Targeting This DTP
Drug Name Drug ID Indication ICD 11 Highest Status REF
Org-24461 DMCMS7V Schizophrenia 6A20 Preclinical [13]
Organon DMERWUC Schizophrenia 6A20 Preclinical [13]
Organon-2 DM46QXZ Schizophrenia 6A20 Preclinical [13]
Organon-3 DM07EU4 Schizophrenia 6A20 Preclinical [13]
SSR-103800 DM84EOW Schizophrenia 6A20 Preclinical [13]
SSR-504734 DMQTR4I Schizophrenia 6A20 Preclinical [13]
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⏷ Show the Full List of 6 Preclinical Drug(s)
10 Investigative Drug(s) Targeting This DTP
Drug Name Drug ID Indication ICD 11 Highest Status REF
AS-1522489-00 DM7A8PX Dementia 6D80-6D86 Investigative [9]
GSK931145 DMIDQ8B Discovery agent N.A. Investigative [9]
LY2365109 DMBFLOJ Discovery agent N.A. Investigative [9]
RO-4840700 DMC0V25 Schizophrenia 6A20 Investigative [9]
[35S]ACPPB DMVUEYM Discovery agent N.A. Investigative [14]
[3H](R)-NPTS DMRPS2X Discovery agent N.A. Investigative [15]
[3H]GSK931145 DMU6A3W Discovery agent N.A. Investigative [16]
[3H]N-methyl-SSR504734 DMX4RJ8 Discovery agent N.A. Investigative [9]
[3H]NFPS DM6PO49 Discovery agent N.A. Investigative [9]
[3H]SB-733993 DMUS7EH Discovery agent N.A. Investigative [16]
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⏷ Show the Full List of 10 Investigative Drug(s)

References

1 Efficacy and safety of the novel glycine transporter inhibitor BI 425809 once daily in patients with schizophrenia: a double-blind, randomised, placebo-controlled phase 2 study. Lancet Psychiatry. 2021 Mar;8(3):191-201.
2 Effects of the Glycine Transporter-1 Inhibitor Iclepertin (BI 425809) on Sensory Processing, Neural Network Function, and Cognition in Animal Models Related to Schizophrenia. J Pharmacol Exp Ther. 2022 Aug;382(2):223-232.
3 Clinical pipeline report, company report or official report of Roche (2009).
4 Glycine transporters as novel therapeutic targets in schizophrenia, alcohol dependence and pain. Nat Rev Drug Discov. 2013 Nov;12(11):866-85.
5 The 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.
6 ALX 5407: a potent, selective inhibitor of the hGlyT1 glycine transporter. Mol Pharmacol. 2001 Dec;60(6):1414-20.
7 Identification of an Orally Bioavailable, Potent, and Selective Inhibitor of GlyT1. ACS Med Chem Lett. 2010 October 14; 1(7): 350-354.
8 Glycine Transport Inhibitors for the Treatment of Schizophrenia. Open Med Chem J. 2010; 4: 10-19.
9 URL: 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).
10 Characterization of the novel GlyT1 PET tracer [18F]MK-6577 in humans. Synapse. 2015 Jan;69(1):33-40.
11 Glycine transporter-1 inhibitors: a patent review (2011-2016).Expert Opin Ther Pat. 2018 Mar;28(3):197-210.
12 Clinical pipeline report, company report or official report of GlaxoSmithKline (2009).
13 The pipeline and future of drug development in schizophrenia. Mol Psychiatry. 2007 Oct;12(10):904-22.
14 A 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.
15 [3H]-(R)-NPTS, a radioligand for the type 1 glycine transporter. Bioorg Med Chem Lett. 2003 Apr 7;13(7):1291-2.
16 Pharmacological characterisation of the GlyT-1 glycine transporter using two novel radioligands. Neuropharmacology. 2010 Nov;59(6):558-65.
17 Mutation in SLC6A9 encoding a glycine transporter causes a novel form of non-ketotic hyperglycinemia in humans. Hum Genet. 2016 Nov;135(11):1263-1268.
18 Glycine is taken up through GLYT1 and GLYT2 transporters into mouse spinal cord axon terminals and causes vesicular and carrier-mediated release of its proposed co-transmitter GABA. J Neurochem. 2001 Mar;76(6):1823-32.