Target Information

Target General Infomation
Target ID
T51452
Former ID
TTDR01177
Target Name
Gamma-aminobutyric-acid receptor alpha-2 subunit
Gene Name
GABRA2
Synonyms
GABA(A)Gamma-aminobutyric-acid receptor alpha-2 subunit precursor receptor; GABA-A receptor alpha 2; GABRA2
Target Type
Discontinued
Disease Alcohol use disorders [ICD9: 303; ICD10: F10.2]
Neuropathic pain [ICD9: 356.0, 356.8; ICD10: G64, G90.0]
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
Neurotransmitter receptor
Target Validation
T51452
UniProt ID
P47869
Sequence
MKTKLNIYNMQFLLFVFLVWDPARLVLANIQEDEAKNNITIFTRILDRLLDGYDNRLRPG
LGDSITEVFTNIYVTSFGPVSDTDMEYTIDVFFRQKWKDERLKFKGPMNILRLNNLMASK
IWTPDTFFHNGKKSVAHNMTMPNKLLRIQDDGTLLYTMRLTVQAECPMHLEDFPMDAHSC
PLKFGSYAYTTSEVTYIWTYNASDSVQVAPDGSRLNQYDLLGQSIGKETIKSSTGEYTVM
TAHFHLKRKIGYFVIQTYLPCIMTVILSQVSFWLNRESVPARTVFGVTTVLTMTTLSISA
RNSLPKVAYATAMDWFIAVCYAFVFSALIEFATVNYFTKRGWAWDGKSVVNDKKKEKASV
MIQNNAYAVAVANYAPNLSKDPVLSTISKSATTPEPNKKPENKPAEAKKTFNSVSKIDRM
SRIVFPVLFGTFNLVYWATYLNREPVLGVSP
Drugs and Mode of Action
Drug(s) PF-4480682 Drug Info Discontinued in Phase 2 Neuropathic pain [548430]
CGS-17867A Drug Info Terminated Alcohol use disorders [544711]
Inhibitor (2E,4S)-4-ammoniopent-2-enoate Drug Info [533514]
(4R)-4-ammoniopentanoate Drug Info [533514]
(4S)-4-ammoniopentanoate Drug Info [533514]
3-(benzyloxy)-9H-pyrido[3,4-b]indole Drug Info [531188]
3-(hexa-1,3-dienyloxy)-9H-pyrido[3,4-b]indole Drug Info [531188]
3-(isopentyloxy)-9H-pyrido[3,4-b]indole Drug Info [531188]
3-butoxy-9H-pyrido[3,4-b]indole Drug Info [531188]
3-Ethoxy-9H-beta-carboline Drug Info [534660]
3-ethoxy-9H-pyrido[3,4-b]indole Drug Info [531188]
3-isobutoxy-9H-pyrido[3,4-b]indole Drug Info [531188]
3-propoxy-9H-pyrido[3,4-b]indole Drug Info [531188]
5-[(1R)-1-ammonioethyl]isoxazol-3-olate Drug Info [533514]
5-[(1S)-1-ammonioethyl]isoxazol-3-olate Drug Info [533514]
AMENTOFLAVONE Drug Info [526653]
Barbituric acid derivative Drug Info [551407]
Beta-Carboline-3-carboxylic acid t-butyl ester Drug Info [531188]
CGS-17867A Drug Info [527100]
CI-218872 Drug Info [531188]
Ethyl 6-iodo-9H-pyrido[3,4-b]indole-3-carboxylate Drug Info [531188]
Ethyl 9H-pyrido[3,4-b]indole-3-carboxylate Drug Info [531188]
GAMMA-AMINO-BUTANOIC ACID Drug Info [533580]
L-655708 Drug Info [527005]
Ro-151310 Drug Info [531044]
Ro-154513 Drug Info [534122]
Ro-4938581 Drug Info [530391]
RY-066 Drug Info [534718]
Sec-butyl 9H-pyrido[3,4-b]indole-3-carboxylate Drug Info [531188]
Modulator (allosteric modulator) alpha3IA Drug Info [543809]
alpha5IA Drug Info [543809]
DMCM Drug Info [543809]
tetrahydrodeoxycorticosterone Drug Info [543809]
TP003 Drug Info [543809]
[11C]flumazenil Drug Info [543809]
[18F]fluoroethylflumazenil Drug Info [543809]
[3H]CGS8216 Drug Info [543809]
Agonist isonipecotic acid Drug Info [543809]
piperidine-4-sulphonic acid Drug Info [543809]
[3H]muscimol Drug Info [543809]
Modulator MK-0343 Drug Info
MRK016 Drug Info
PF-4480682 Drug Info [550179]
Blocker (channel blocker) TBPS Drug Info [543809]
[35S]TBPS Drug Info [543809]
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 544711Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800000696)
Ref 548430Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800025530)
Ref 526653Bioorg Med Chem Lett. 2003 Jul 21;13(14):2281-4.Semisynthetic preparation of amentoflavone: A negative modulator at GABA(A) receptors.
Ref 527005J 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 527100Bioorg Med Chem Lett. 2004 Jul 5;14(13):3441-4.2,5-Dihydropyrazolo[4,3-c]pyridin-3-ones: functionally selective benzodiazepine binding site ligands on the GABAA receptor.
Ref 530391Bioorg 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 531044Bioorg Med Chem. 2010 Nov 15;18(22):7731-8. Epub 2010 Jun 1.The GABA(A) receptor as a target for photochromic molecules.
Ref 531188Bioorg 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 533514J Med Chem. 1981 Dec;24(12):1377-83.gamma-Aminobutyric acid agonists, antagonists, and uptake inhibitors. Design and therapeutic aspects.
Ref 533580J Med Chem. 1980 Jun;23(6):702-4.New anticonvulsants: Schiff bases of gamma-aminobutyric acid and gamma-aminobutyramide.
Ref 534122J 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 534660J Med Chem. 1998 Jul 2;41(14):2537-52.Synthesis and evaluation of analogues of the partial agonist 6-(propyloxy)-4-(methoxymethyl)-beta-carboline-3-carboxylic acid ethyl ester (6-PBC) and the full agonist 6-(benzyloxy)-4-(methoxymethyl)-beta-carboline-3-carboxylic acid ethyl ester (Zk 93423) at wild type and recombinant GABAA receptors.
Ref 534718J 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 543809(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: 405).
Ref 550179WO patent application no. 2014,1515,17, Methods of improving microvascular integrity.
Ref 551407Whiting 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.

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