Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTPRKM0)

• DTT Name: GABA transporter GAT-1 (SLC6A1)
• Synonyms: Solute carrier family 6 member 1; Sodium- and chloride-dependent GABA transporter 1; GAT1; GAT-1; GABT1; GABATR; GABA transporter 1
• Gene Name: SLC6A1
• DTT Type: Successful target; [1]
• BioChemical Class: Neurotransmitter:sodium symporter
• UniProt ID: SC6A1_HUMAN
• TTD ID: T62184
• Sequence:
  MATNGSKVADGQISTEVSEAPVANDKPKTLVVKVQKKAADLPDRDTWKGRFDFLMSCVGY
  AIGLGNVWRFPYLCGKNGGGAFLIPYFLTLIFAGVPLFLLECSLGQYTSIGGLGVWKLAP
  MFKGVGLAAAVLSFWLNIYYIVIISWAIYYLYNSFTTTLPWKQCDNPWNTDRCFSNYSMV
  NTTNMTSAVVEFWERNMHQMTDGLDKPGQIRWPLAITLAIAWILVYFCIWKGVGWTGKVV
  YFSATYPYIMLIILFFRGVTLPGAKEGILFYITPNFRKLSDSEVWLDAATQIFFSYGLGL
  GSLIALGSYNSFHNNVYRDSIIVCCINSCTSMFAGFVIFSIVGFMAHVTKRSIADVAASG
  PGLAFLAYPEAVTQLPISPLWAILFFSMLLMLGIDSQFCTVEGFITALVDEYPRLLRNRR
  ELFIAAVCIISYLIGLSNITQGGIYVFKLFDYYSASGMSLLFLVFFECVSISWFYGVNRF
  YDNIQEMVGSRPCIWWKLCWSFFTPIIVAGVFIFSAVQMTPLTMGNYVFPKWGQGVGWLM
  ALSSMVLIPGYMAYMFLTLKGSLKQRIQVMVQPSEDIVRPENGPEQPQAGSSTSKEAYI
• Function: Terminates the action of GABA by its high affinity sodium-dependent reuptake into presynaptic terminals.
• KEGG Pathway: GABAergic synapse (hsa04727)
• Reactome Pathway: Na+/Cl- dependent neurotransmitter transporters (R-HSA-442660)

Molecular Interaction Atlas (MIA) of This DTT

2 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Metadoxine	DMM4QOJ	Multiple myeloma	2A83	Approved	[2]
Tiagabine	DMKSQG0	Epilepsy	8A60-8A68	Approved	[1]

2 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
GSK683699	DMTW79H	Inflammatory bowel disease	DD72	Phase 2	[3]
CI-966	DM8T2KA	Convulsion	8A68.Z	Phase 1	[4]

10 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
(R)-EF-1520	DM297MU	Discovery agent	N.A.	Investigative	[1]
(R)-nipecotic acid	DMWGB40	Discovery agent	N.A.	Investigative	[3]
(R/S) EF-1500	DMYDG27	Discovery agent	N.A.	Investigative	[1]
(S)-EF-1520	DM0EQTM	Discovery agent	N.A.	Investigative	[1]
(S)-Piperidine-3-carboxylic acid	DMST89H	Discovery agent	N.A.	Investigative	[3]
2,4-Diamino-butyric acid(GABA)	DMAOGBP	Discovery agent	N.A.	Investigative	[5]
4-Hydroxy-piperidine-3-carboxylic acid	DM9VQ0T	Discovery agent	N.A.	Investigative	[6]
LU32-176B	DM2YOVC	Discovery agent	N.A.	Investigative	[7]
NIPECOTIC ACID	DMPV450	Discovery agent	N.A.	Investigative	[8]
SKF89976A	DM0WNHQ	Discovery agent	N.A.	Investigative	[1]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Multiple myeloma	2C82	Bone marrow	4.99E-02	-0.24	-0.62

The Drug Transporter (DTP) Role of This DTT

• DTT DTP Name: Sodium- and chloride-dependent GABA transporter 1 (SLC6A1) DTP Info
• Gene Name: SLC6A1

1 Clinical Trial Drug(s) Transported by This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
GSK683699	DMTW79H	Inflammatory bowel disease	DD72	Phase 2	[9]

References

• [1] 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: 929).
• [2] Company report (Alcobra pharma)
• [3] Novel secoergoline derivatives inhibit both GABA and glutamate uptake in rat brain homogenates: synthesis, in vitro pharmacology, and modeling. J Med Chem. 2004 Nov 4;47(23):5620-9.
• [4] Tiagabine, SK&F 89976-A, CI-966, and NNC-711 are selective for the cloned GABA transporter GAT-1. Eur J Pharmacol. 1994 Oct 14;269(2):219-24.
• [5] Glycine antagonists. Synthesis, structure, and biological effects of some bicyclic 5-isoxazolol zwitterions. J Med Chem. 1986 Feb;29(2):224-9.
• [6] Hydroxy- and amino-substituted piperidinecarboxylic acids as gamma-aminobutyric acid agonists and uptake inhibitors. J Med Chem. 1982 Oct;25(10):1157-62.
• [7] First demonstration of a functional role for central nervous system betaine/{gamma}-aminobutyric acid transporter (mGAT2) based on synergistic anti... J Pharmacol Exp Ther. 2005 Feb;312(2):866-74.
• [8] Epimeric cis-decahydroquinoline-5-carboxylic acids: effects on gamma-aminobutyric acid uptake and receptor binding in vitro. J Med Chem. 1981 Jul;24(7):788-94.
• [9] Mutations in the GABA Transporter SLC6A1 Cause Epilepsy with Myoclonic-Atonic Seizures. Am J Hum Genet. 2015 May 7;96(5):808-15.