Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTT2LD9)

• DTT Name: GABA transaminase (ABAT)
• Synonyms: L-AIBAT; Gamma-amino-N-butyrate transaminase; GABA-T; GABA-AT; GABA aminotransferase; ABAT; (S)-3-amino-2-methylpropionate transaminase
• Gene Name: ABAT
• DTT Type: Successful target; [1]
• Related Disease:
  Brain cancer [ICD-11: 2A00]
  Epilepsy/seizure [ICD-11: 8A61-8A6Z]
  Epileptic encephalopathy [ICD-11: 8A62]
  Mineral deficiency [ICD-11: 5B5K]
  Nutritional deficiency [ICD-11: 5B50-5B71]
• BioChemical Class: Transaminase
• UniProt ID: GABT_HUMAN
• TTD ID: T59045
• EC Number: EC 2.6.1.19
• Sequence:
  MASMLLAQRLACSFQHSYRLLVPGSRHISQAAAKVDVEFDYDGPLMKTEVPGPRSQELMK
  QLNIIQNAEAVHFFCNYEESRGNYLVDVDGNRMLDLYSQISSVPIGYSHPALLKLIQQPQ
  NASMFVNRPALGILPPENFVEKLRQSLLSVAPKGMSQLITMACGSCSNENALKTIFMWYR
  SKERGQRGFSQEELETCMINQAPGCPDYSILSFMGAFHGRTMGCLATTHSKAIHKIDIPS
  FDWPIAPFPRLKYPLEEFVKENQQEEARCLEEVEDLIVKYRKKKKTVAGIIVEPIQSEGG
  DNHASDDFFRKLRDIARKHGCAFLVDEVQTGGGCTGKFWAHEHWGLDDPADVMTFSKKMM
  TGGFFHKEEFRPNAPYRIFNTWLGDPSKNLLLAEVINIIKREDLLNNAAHAGKALLTGLL
  DLQARYPQFISRVRGRGTFCSFDTPDDSIRNKLILIARNKGVVLGGCGDKSIRFRPTLVF
  RDHHAHLFLNIFSDILADFK
• Function: Catalyzes the conversion of gamma-aminobutyrate and L- beta-aminoisobutyrate to succinate semialdehyde and methylmalonate semialdehyde, respectively. Can also convert delta-aminovalerate andbeta-alanine.
• KEGG Pathway:
  Alanine, aspartate and glutamate metabolism (hsa00250)
  Valine, leucine and isoleucine degradation (hsa00280)
  beta-Alanine metabolism (hsa00410)
  Propanoate metabolism (hsa00640)
  Butanoate metabolism (hsa00650)
  Metabolic pathways (hsa01100)
  GABAergic synapse (hsa04727)
• Reactome Pathway: Degradation of GABA (R-HSA-916853)
• BioCyc Pathway: MetaCyc:HS02477-MON

Molecular Interaction Atlas (MIA) of This DTT

5 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Divalproex sodium	DM4RK0G	Seizure disorder	8A6Z	Approved	[1]
L-alanine	DMZDN4W	Dietary shortage	5B5K	Approved	[1]
Pyridoxal Phosphate	DMO2K0J	Malnutrition	5B50-5B71	Approved	[1]
Pyruvic acid	DM7Q41G	Malnutrition	5B50-5B71	Approved	[1]
Vigabatrin	DMYT0OG	Complex partial seizure	8A68.0	Approved	[2], [3], [4], [5]

3 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
CPP-115	DMK9NQI	Tourette syndrome	8A05.00	Phase 2	[6]
K-828-AB	DMJLNZQ	Dementia	6D80-6D86	Phase 2	[7]
CPP -15	DMQCHU3	Infantile spasm	8A62.0	Phase 1	[6]

2 Patented Agent(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
4-hydroxybenzaldehyde	DM471P5	Discovery agent	N.A.	Patented	[8]
T83193	DMHO29Y	Discovery agent	N.A.	Patented	[9]

11 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
(4e)-4-Aminohex-4-Enoic Acid	DMG27K1	Discovery agent	N.A.	Investigative	[10]
1-(4-hydroxyphenyl)prop-2-en-1-one	DM145QS	Discovery agent	N.A.	Investigative	[9]
3-chloro-1-(4-hydroxyphenyl)propan-1-one	DM9OGNE	Discovery agent	N.A.	Investigative	[8]
4-Amino Hexanoic Acid	DMYX34S	Discovery agent	N.A.	Investigative	[10]
4-hydroxy-3-nitrobenzaldehyde	DMR0S8X	Discovery agent	N.A.	Investigative	[9]
4-hydroxybenzylamine	DMJVPF0	Discovery agent	N.A.	Investigative	[9]
Acetate Ion	DMD08RH	Discovery agent	N.A.	Investigative	[10]
Gamma-acetylenic GABA	DMFSXOM	Discovery agent	N.A.	Investigative	[11]
NIPECOTIC ACID	DMPV450	Discovery agent	N.A.	Investigative	[12]
OXAMATE	DMTYBC9	Discovery agent	N.A.	Investigative	[12]
Sodium valproate	DMX6PLV	Discovery agent	N.A.	Investigative	[13]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Glioma	2C82	Brainstem tissue	5.15E-01	0.74	0.76
Glioma	2C82	White matter	1.37E-01	0.59	0.46

References

• [1] DrugBank: a knowledgebase for drugs, drug actions and drug targets. Nucleic Acids Res. 2008 Jan;36(Database issue):D901-6.
• [2] Hughes B: 2009 FDA drug approvals. Nat Rev Drug Discov. 2010 Feb;9(2):89-92.
• [3] Glutamate- and GABA-based CNS therapeutics. Curr Opin Pharmacol. 2006 Feb;6(1):7-17.
• [4] Gamma-vinyl GABA, an irreversible inhibitor of GABA transaminase, alters the acquisition and expression of cocaine-induced sensitization in male rats. Synapse. 2002 Dec 15;46(4):240-50.
• [5] Vigabatrin for refractory complex partial seizures: multicenter single-blind study with long-term follow-up. Neurology. 1987 Feb;37(2):184-9.
• [6] Clinical pipeline report, company report or official report of Catalyst Pharma.
• [7] Phase II clinical trial of K-828-AB for treating behavioral and psychological symptoms of dementia. Kowa Co. Ltd.
• [8] Inactivation of GABA transaminase by 3-chloro-1-(4-hydroxyphenyl)propan-1-one. Bioorg Med Chem Lett. 2009 Feb 1;19(3):731-4.
• [9] Inhibition of GABA shunt enzymes' activity by 4-hydroxybenzaldehyde derivatives. Bioorg Med Chem Lett. 2006 Feb;16(3):592-5.
• [10] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
• [11] Treatment of Huntington disease with gamma-acetylenic GABA an irreversible inhibitor of GABA-transaminase: increased CSF GABA and homocarnosine without clinical amelioration. Neurology. 1981 Feb;31(2):207-11.
• [12] Aminomethyl-1,2,4-benzothiadiazines as potential analogues of gamma-aminobutyric acid. Unexpected discovery of a taurine antagonist. J Med Chem. 1982 Feb;25(2):113-6.
• [13] Influence of a GABA transaminase inhibitor on central nervous system oxygen toxicity. Aviat Space Environ Med. 1978 Jul;49(7):877-9.