Target Information

Target General Infomation
Target ID
T62292
Former ID
TTDR01178
Target Name
Gamma-aminobutyric-acid receptor alpha-3 subunit
Gene Name
GABRA3
Synonyms
GABA(A)Gamma-aminobutyric-acid receptor alpha-3 subunit precursor receptor; GABA-A receptor alpha 3; GABRA3
Target Type
Clinical Trial
Disease Anxiety disorder [ICD9: 300, 311; ICD10: F32, F40-F42]
Anxiety disorder; Schizophrenia [ICD9: 295, 300; ICD10: F20, F40-F42]
Sleep disorders [ICD9: 307.4, 327, 780.5; ICD10: F51, G47]
Unspecified [ICD code not available]
Function
GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel.
BioChemical Class
Ligand-gated ion channel
Target Validation
T62292
UniProt ID
P34903
Sequence
MIITQTSHCYMTSLGILFLINILPGTTGQGESRRQEPGDFVKQDIGGLSPKHAPDIPDDS
TDNITIFTRILDRLLDGYDNRLRPGLGDAVTEVKTDIYVTSFGPVSDTDMEYTIDVFFRQ
TWHDERLKFDGPMKILPLNNLLASKIWTPDTFFHNGKKSVAHNMTTPNKLLRLVDNGTLL
YTMRLTIHAECPMHLEDFPMDVHACPLKFGSYAYTTAEVVYSWTLGKNKSVEVAQDGSRL
NQYDLLGHVVGTEIIRSSTGEYVVMTTHFHLKRKIGYFVIQTYLPCIMTVILSQVSFWLN
RESVPARTVFGVTTVLTMTTLSISARNSLPKVAYATAMDWFIAVCYAFVFSALIEFATVN
YFTKRSWAWEGKKVPEALEMKKKTPAAPAKKTSTTFNIVGTTYPINLAKDTEFSTISKGA
APSASSTPTIIASPKATYVQDSPTETKTYNSVSKVDKISRIIFPVLFAIFNLVYWATYVN
RESAIKGMIRKQ
Drugs and Mode of Action
Drug(s) Adipiplon Drug Info Phase 2 Sleep disorders [1]
NS-2710 Drug Info Phase 2 Anxiety disorder [2]
AZD6280 Drug Info Discontinued in Phase 1 Anxiety disorder; Schizophrenia [3]
Inhibitor (2E,4S)-4-ammoniopent-2-enoate Drug Info [4]
(4R)-4-ammoniopentanoate Drug Info [4]
(4S)-4-ammoniopentanoate Drug Info [4]
3-(benzyloxy)-9H-pyrido[3,4-b]indole Drug Info [5]
3-(hexa-1,3-dienyloxy)-9H-pyrido[3,4-b]indole Drug Info [5]
3-(isopentyloxy)-9H-pyrido[3,4-b]indole Drug Info [5]
3-butoxy-9H-pyrido[3,4-b]indole Drug Info [5]
3-ethoxy-9H-pyrido[3,4-b]indole Drug Info [5]
3-isobutoxy-9H-pyrido[3,4-b]indole Drug Info [5]
3-propoxy-9H-pyrido[3,4-b]indole Drug Info [5]
5-[(1R)-1-ammonioethyl]isoxazol-3-olate Drug Info [4]
5-[(1S)-1-ammonioethyl]isoxazol-3-olate Drug Info [4]
6-benzyl-3-ethoxycarbonyl-4-quinolone Drug Info [6]
6-bromo-3-ethoxycarbonyl-4-quinolone Drug Info [6]
6-ethyl-3-(3-methylbutoxycarbonyl)-4-quinolone Drug Info [6]
AMENTOFLAVONE Drug Info [7]
Barbituric acid derivative Drug Info [8]
Beta-Carboline-3-carboxylic acid t-butyl ester Drug Info [5]
CI-218872 Drug Info [5]
Ethyl 6-iodo-9H-pyrido[3,4-b]indole-3-carboxylate Drug Info [5]
Ethyl 9H-pyrido[3,4-b]indole-3-carboxylate Drug Info [5]
GAMMA-AMINO-BUTANOIC ACID Drug Info [9]
L-655708 Drug Info [10]
Ro-151310 Drug Info [11]
Ro-154513 Drug Info [12]
Ro-4938581 Drug Info [13]
RY-066 Drug Info [14]
Sec-butyl 9H-pyrido[3,4-b]indole-3-carboxylate Drug Info [5]
Modulator Adipiplon Drug Info [15]
AZD6280 Drug Info
MK-0343 Drug Info
MRK016 Drug Info
NS-2710 Drug Info [2]
Modulator (allosteric modulator) alpha3IA Drug Info [16]
alpha5IA Drug Info [16]
DMCM Drug Info [16]
tetrahydrodeoxycorticosterone Drug Info [16]
TP003 Drug Info [16]
[11C]flumazenil Drug Info [16]
[18F]fluoroethylflumazenil Drug Info [16]
[3H]CGS8216 Drug Info [16]
Agonist isonipecotic acid Drug Info [16]
piperidine-4-sulphonic acid Drug Info [16]
[3H]muscimol Drug Info [16]
Blocker (channel blocker) TBPS Drug Info [16]
[35S]TBPS Drug Info [16]
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM)
TEP EXP Info
Pathways
KEGG Pathway Neuroactive ligand-receptor interaction
Retrograde endocannabinoid signaling
GABAergic synapse
Morphine addiction
Nicotine addiction
Reactome Ligand-gated ion channel transport
GABA A receptor activation
WikiPathways Neurotransmitter Receptor Binding And Downstream Transmission In The Postsynaptic Cell
Iron uptake and transport
References
REF 1ClinicalTrials.gov (NCT00683436) Efficacy and Safety Study of Adipiplon, Placebo and an Active Control in Primary Insomniacs. U.S. National Institutes of Health.
REF 2GABAA receptor subtype-selective modulators. I. alpha2/alpha3-selective agonists as non-sedating anxiolytics. Curr Top Med Chem. 2011;11(9):1176-202.
REF 3Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800027607)
REF 4J Med Chem. 1981 Dec;24(12):1377-83.gamma-Aminobutyric acid agonists, antagonists, and uptake inhibitors. Design and therapeutic aspects.
REF 5Bioorg Med Chem. 2010 Nov 1;18(21):7548-64. Epub 2010 Sep 29.Design, synthesis, and subtype selectivity of 3,6-disubstituted |A-carbolines at Bz/GABA(A)ergic receptors. SAR and studies directed toward agents for treatment of alcohol abuse.
REF 6J Med Chem. 2006 Apr 20;49(8):2526-33.4-quinolone derivatives: high-affinity ligands at the benzodiazepine site of brain GABA A receptors. synthesis, pharmacology, and pharmacophore modeling.
REF 7Bioorg Med Chem Lett. 2003 Jul 21;13(14):2281-4.Semisynthetic preparation of amentoflavone: A negative modulator at GABA(A) receptors.
REF 8Whiting PJ: The <span class="caps">GABAA</span> receptor gene family: new opportunities for drug development. Curr Opin Drug Discov Devel. 2003 Sep;6(5):648-57.
REF 9J Med Chem. 1980 Jun;23(6):702-4.New anticonvulsants: Schiff bases of gamma-aminobutyric acid and gamma-aminobutyramide.
REF 10J Med Chem. 2004 Mar 25;47(7):1807-22.3-phenyl-6-(2-pyridyl)methyloxy-1,2,4-triazolo[3,4-a]phthalazines and analogues: high-affinity gamma-aminobutyric acid-A benzodiazepine receptor ligands with alpha 2, alpha 3, and alpha 5-subtype binding selectivity over alpha 1.
REF 11Bioorg Med Chem. 2010 Nov 15;18(22):7731-8. Epub 2010 Jun 1.The GABA(A) receptor as a target for photochromic molecules.
REF 12J Med Chem. 1996 Apr 26;39(9):1928-34.Synthesis and pharmacological properties of novel 8-substituted imidazobenzodiazepines: high-affinity, selective probes for alpha 5-containing GABAA receptors.
REF 13Bioorg Med Chem Lett. 2009 Oct 15;19(20):5940-4. Epub 2009 Aug 15.The discovery and unique pharmacological profile of RO4938581 and RO4882224 as potent and selective GABAA alpha5 inverse agonists for the treatment of cognitive dysfunction.
REF 14J Med Chem. 1998 Oct 8;41(21):4130-42.Predictive models for GABAA/benzodiazepine receptor subtypes: studies of quantitative structure-activity relationships for imidazobenzodiazepines at five recombinant GABAA/benzodiazepine receptor subtypes [alphaxbeta3gamma2 (x = 1-3, 5, and 6)] via comparative molecular field analysis.
REF 15Discriminative stimulus properties of GABAA receptor positive allosteric modulators TPA023, ocinaplon and NG2-73 in rats trained to discriminate chlordiazepoxide or zolpidem. Eur J Pharmacol. 2011 Oct 1;668(1-2):190-3.
REF 16(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: 406).

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