Target Information
| Target General Information | Top | |||||
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| Target ID |
T59045
(Former ID: TTDS00024)
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| Target Name |
GABA transaminase (ABAT)
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| Synonyms |
L-AIBAT; Gamma-amino-N-butyrate transaminase; GABA-T; GABA-AT; GABA aminotransferase; ABAT; (S)-3-amino-2-methylpropionate transaminase
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| Gene Name |
ABAT
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| Target Type |
Successful target
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[1] | ||||
| Disease | [+] 5 Target-related Diseases | + | ||||
| 1 | Brain cancer [ICD-11: 2A00] | |||||
| 2 | Epilepsy/seizure [ICD-11: 8A61-8A6Z] | |||||
| 3 | Epileptic encephalopathy [ICD-11: 8A62] | |||||
| 4 | Mineral deficiency [ICD-11: 5B5K] | |||||
| 5 | Nutritional deficiency [ICD-11: 5B50-5B71] | |||||
| 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.
Click to Show/Hide
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| BioChemical Class |
Transaminase
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| UniProt ID | ||||||
| EC Number |
EC 2.6.1.19
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| Sequence |
MASMLLAQRLACSFQHSYRLLVPGSRHISQAAAKVDVEFDYDGPLMKTEVPGPRSQELMK
QLNIIQNAEAVHFFCNYEESRGNYLVDVDGNRMLDLYSQISSVPIGYSHPALLKLIQQPQ NASMFVNRPALGILPPENFVEKLRQSLLSVAPKGMSQLITMACGSCSNENALKTIFMWYR SKERGQRGFSQEELETCMINQAPGCPDYSILSFMGAFHGRTMGCLATTHSKAIHKIDIPS FDWPIAPFPRLKYPLEEFVKENQQEEARCLEEVEDLIVKYRKKKKTVAGIIVEPIQSEGG DNHASDDFFRKLRDIARKHGCAFLVDEVQTGGGCTGKFWAHEHWGLDDPADVMTFSKKMM TGGFFHKEEFRPNAPYRIFNTWLGDPSKNLLLAEVINIIKREDLLNNAAHAGKALLTGLL DLQARYPQFISRVRGRGTFCSFDTPDDSIRNKLILIARNKGVVLGGCGDKSIRFRPTLVF RDHHAHLFLNIFSDILADFK Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | AlphaFold | ||||
| HIT2.0 ID | T68XXK | |||||
| Drugs and Modes of Action | Top | |||||
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| Approved Drug(s) | [+] 5 Approved Drugs | + | ||||
| 1 | Divalproex sodium | Drug Info | Approved | Seizure disorder | [2] | |
| 2 | L-Alanine | Drug Info | Approved | Glioma | [3], [4], [5] | |
| 3 | Pyridoxal Phosphate | Drug Info | Approved | Malnutrition | [6], [7] | |
| 4 | Pyruvic acid | Drug Info | Approved | Malnutrition | [8], [9] | |
| 5 | Vigabatrin | Drug Info | Approved | Complex partial seizure | [10], [11] | |
| Clinical Trial Drug(s) | [+] 3 Clinical Trial Drugs | + | ||||
| 1 | CPP-115 | Drug Info | Phase 2 | Tourette syndrome | [12] | |
| 2 | K-828-AB | Drug Info | Phase 2 | Dementia | [13] | |
| 3 | CPP -15 | Drug Info | Phase 1 | Infantile spasm | [14] | |
| Mode of Action | [+] 2 Modes of Action | + | ||||
| Inhibitor | [+] 20 Inhibitor drugs | + | ||||
| 1 | Divalproex sodium | Drug Info | [1] | |||
| 2 | L-Alanine | Drug Info | [1] | |||
| 3 | Pyridoxal Phosphate | Drug Info | [1] | |||
| 4 | Pyruvic acid | Drug Info | [1] | |||
| 5 | Vigabatrin | Drug Info | [11], [15], [16], [17] | |||
| 6 | CPP-115 | Drug Info | [18] | |||
| 7 | K-828-AB | Drug Info | [19] | |||
| 8 | 4-hydroxybenzaldehyde | Drug Info | [20] | |||
| 9 | T83193 | Drug Info | [21] | |||
| 10 | (4e)-4-Aminohex-4-Enoic Acid | Drug Info | [22] | |||
| 11 | 1-(4-hydroxyphenyl)prop-2-en-1-one | Drug Info | [21] | |||
| 12 | 3-chloro-1-(4-hydroxyphenyl)propan-1-one | Drug Info | [20] | |||
| 13 | 4-Amino Hexanoic Acid | Drug Info | [22] | |||
| 14 | 4-hydroxy-3-nitrobenzaldehyde | Drug Info | [21] | |||
| 15 | 4-hydroxybenzylamine | Drug Info | [21] | |||
| 16 | Acetate Ion | Drug Info | [22] | |||
| 17 | Gamma-acetylenic GABA | Drug Info | [23] | |||
| 18 | NIPECOTIC ACID | Drug Info | [24] | |||
| 19 | OXAMATE | Drug Info | [24] | |||
| 20 | Sodium valproate | Drug Info | [25] | |||
| Modulator | [+] 1 Modulator drugs | + | ||||
| 1 | CPP -15 | Drug Info | [18] | |||
| Chemical Structure based Activity Landscape of Target | Top |
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| Drug Property Profile of Target | Top | |
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| (1) Molecular Weight (mw) based Drug Clustering | (2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering | |
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| (3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering | (4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering | |
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| (5) Rotatable Bond Count (rotbonds) based Drug Clustering | (6) Topological Polar Surface Area (polararea) based Drug Clustering | |
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| "RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five | ||
| Target Poor or Non Binders | Top | |||||
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| Target Poor or Non Binders | ||||||
| Target Profiles in Patients | Top | |||||
|---|---|---|---|---|---|---|
| Target Expression Profile (TEP) | ||||||
| Target Affiliated Biological Pathways | Top | |||||
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| BioCyc | [+] 4 BioCyc Pathways | + | ||||
| 1 | GABA shunt | |||||
| 2 | Valine degradation | |||||
| 3 | Beta-alanine degradation | |||||
| 4 | 4-aminobutyrate degradation | |||||
| KEGG Pathway | [+] 7 KEGG Pathways | + | ||||
| 1 | Alanine, aspartate and glutamate metabolism | |||||
| 2 | Valine, leucine and isoleucine degradation | |||||
| 3 | beta-Alanine metabolism | |||||
| 4 | Propanoate metabolism | |||||
| 5 | Butanoate metabolism | |||||
| 6 | Metabolic pathways | |||||
| 7 | GABAergic synapse | |||||
| Panther Pathway | [+] 3 Panther Pathways | + | ||||
| 1 | Aminobutyrate degradation | |||||
| 2 | Pyrimidine Metabolism | |||||
| 3 | Gamma-aminobutyric acid synthesis | |||||
| Pathwhiz Pathway | [+] 5 Pathwhiz Pathways | + | ||||
| 1 | Aspartate Metabolism | |||||
| 2 | Glutamate Metabolism | |||||
| 3 | Beta-Alanine Metabolism | |||||
| 4 | Valine, Leucine and Isoleucine Degradation | |||||
| 5 | Propanoate Metabolism | |||||
| WikiPathways | [+] 2 WikiPathways | + | ||||
| 1 | GABA synthesis, release, reuptake and degradation | |||||
| 2 | Alanine and aspartate metabolism | |||||
| Target-Related Models and Studies | Top | |||||
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| Target Validation | ||||||
| References | Top | |||||
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| REF 1 | DrugBank: a knowledgebase for drugs, drug actions and drug targets. Nucleic Acids Res. 2008 Jan;36(Database issue):D901-6. | |||||
| REF 2 | FDA approved drugs (1996) in CenterWatch | |||||
| REF 3 | 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. (Ligand id: 720). | |||||
| REF 4 | Drug information of L-Alanine, Health Canada, 2008. (drugid: 7638) | |||||
| REF 5 | Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015 | |||||
| REF 6 | 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. (Ligand id: 5249). | |||||
| REF 7 | Drug information of Pyridoxal Phosphate, 2008. eduDrugs. | |||||
| REF 8 | 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. (Ligand id: 4809). | |||||
| REF 9 | FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (ANDA) 065200. | |||||
| REF 10 | 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. (Ligand id: 4821). | |||||
| REF 11 | Hughes B: 2009 FDA drug approvals. Nat Rev Drug Discov. 2010 Feb;9(2):89-92. | |||||
| REF 12 | Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA) | |||||
| REF 13 | Clinical pipeline report, company report or official report of Kowa Co Ltd. | |||||
| REF 14 | Clinical pipeline report, company report or official report of Catalyst Pharma. | |||||
| REF 15 | Glutamate- and GABA-based CNS therapeutics. Curr Opin Pharmacol. 2006 Feb;6(1):7-17. | |||||
| REF 16 | 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. | |||||
| REF 17 | Vigabatrin for refractory complex partial seizures: multicenter single-blind study with long-term follow-up. Neurology. 1987 Feb;37(2):184-9. | |||||
| REF 18 | Clinical pipeline report, company report or official report of Catalyst Pharma. | |||||
| REF 19 | Phase II clinical trial of K-828-AB for treating behavioral and psychological symptoms of dementia. Kowa Co. Ltd. | |||||
| REF 20 | Inactivation of GABA transaminase by 3-chloro-1-(4-hydroxyphenyl)propan-1-one. Bioorg Med Chem Lett. 2009 Feb 1;19(3):731-4. | |||||
| REF 21 | Inhibition of GABA shunt enzymes' activity by 4-hydroxybenzaldehyde derivatives. Bioorg Med Chem Lett. 2006 Feb;16(3):592-5. | |||||
| REF 22 | How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6. | |||||
| REF 23 | 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. | |||||
| REF 24 | 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. | |||||
| REF 25 | Influence of a GABA transaminase inhibitor on central nervous system oxygen toxicity. Aviat Space Environ Med. 1978 Jul;49(7):877-9. | |||||
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