Target Information

Target General Infomation
Target ID
T80387
Former ID
TTDS00410
Target Name
Gamma-aminobutyric acid receptor subunit beta-2
Gene Name
GABRB2
Synonyms
GABA(A) receptor subunit beta-2; GABRB2
Target Type
Successful
Disease Anxiety disorder [ICD9: 300, 311; ICD10: F32, F40-F42]
Epileptic seizures [ICD9: 345.9, 780.3; ICD10: G40, P90, R56]
Insomnia [ICD9: 307.41, 307.42, 327.0, 780.51, 780.52; ICD10: F51.0, G47.0]
Inflammation [ICD10: E08-E13, E10.2, E11, E11.2, E13.2, I73.9, I80-I82, N00-N29, G89]
Muscle spasm [ICD10: M62.838]
Premenstrual syndrome [ICD10: N94.3]
Function
Component of the heteropentameric receptor for GABA, the major inhibitory neurotransmitter in the vertebrate brain. Functions also as histamine receptor and mediates cellular responses to histamine. Functions as receptor for diazepines and various anesthetics, such as pentobarbital; these are bound at a separate allosteric effector binding site. Functions as ligand- gated chloride channel.
BioChemical Class
Neurotransmitter receptor
Target Validation
T80387
UniProt ID
P47870
Sequence
MWRVRKRGYFGIWSFPLIIAAVCAQSVNDPSNMSLVKETVDRLLKGYDIRLRPDFGGPPV
AVGMNIDIASIDMVSEVNMDYTLTMYFQQAWRDKRLSYNVIPLNLTLDNRVADQLWVPDT
YFLNDKKSFVHGVTVKNRMIRLHPDGTVLYGLRITTTAACMMDLRRYPLDEQNCTLEIES
YGYTTDDIEFYWRGDDNAVTGVTKIELPQFSIVDYKLITKKVVFSTGSYPRLSLSFKLKR
NIGYFILQTYMPSILITILSWVSFWINYDASAARVALGITTVLTMTTINTHLRETLPKIP
YVKAIDMYLMGCFVFVFMALLEYALVNYIFFGRGPQRQKKAAEKAASANNEKMRLDVNKI
FYKDIKQNGTQYRSLWDPTGNLSPTRRTTNYDFSLYTMDPHENILLSTLEIKNEMATSEA
VMGLGDPRSTMLAYDASSIQYRKAGLPRHSFGRNALERHVAQKKSRLRRRASQLKITIPD
LTDVNAIDRWSRIFFPVVFSFFNIVYWLYYVN
Drugs and Mode of Action
Drug(s) Ethchlorvynol Drug Info Approved Insomnia [1], [2]
THIOCOLCHICOSIDE Drug Info Approved Muscle spasm [3]
ZK-93423 Drug Info Phase 3 Epileptic seizures [4], [5]
ALLOPREGNANOLONE Drug Info Phase 2 Discovery agent [6], [7]
ELTANOLONE Drug Info Discontinued in Phase 3 Premenstrual syndrome [8]
U-78875 Drug Info Discontinued in Phase 1 Anxiety disorder [9]
CGS-9896 Drug Info Terminated Discovery agent [10]
Inhibitor (2E,4S)-4-ammoniopent-2-enoate Drug Info [11]
(4R)-4-ammoniopentanoate Drug Info [11]
(4S)-4-ammoniopentanoate Drug Info [11]
(9-Benzyl-9H-purin-6-yl)-cyclopropyl-amine Drug Info [12]
1,1-Dimethyl-5-oxa-spiro[2.4]heptan-4-one Drug Info [13]
1-(4-chlorophenyl)-4-phenyl-1H-imidazole Drug Info [14]
1-Methyl-5-oxa-spiro[2.4]heptan-4-one Drug Info [13]
2-(4-chlorophenyl)-5-phenyl-4-isoxazolin-3-one Drug Info [14]
2-(9-Benzyl-9H-purin-6-ylamino)-ethanol Drug Info [12]
2-Isoxazol-5-yl-3H-imidazo[4,5-c]quinoline Drug Info [15]
2-Oxa-spiro[4.4]nonan-1-one Drug Info [13]
2-Thiophen-2-yl-3H-imidazo[4,5-c]quinoline Drug Info [15]
3,3-Diethyl-dihydro-furan-2-one Drug Info [13]
3,3-Diisopropyl-dihydro-furan-2-one Drug Info [13]
3-amino-3-demethoxythiocolchicine Drug Info [16]
3-butoxycarbonyl-4-quinolone Drug Info [17]
3-butoxycarbonyl-6-ethyl-4-quinolone Drug Info [17]
3-butylaminocarbonyl-6-ethyl-4-quinolone Drug Info [17]
3-carboxy-6-ethyl-4-quinolone Drug Info [17]
3-cyclopentoxycarbonyl-6-ethyl-4-quinolone Drug Info [17]
3-demethoxy-3-D-lyxopyranosylaminothiocolchicine Drug Info [16]
3-demethoxy-3-D-mannopyranosylaminothiocolchicine Drug Info [16]
3-demethoxy-3-D-xylopyranosylaminothiocolchicine Drug Info [16]
3-demethoxy-3-L-fucopyranosylaminothiocolchicine Drug Info [16]
3-demethoxy-3D-glucopyranosylaminothiocolchicine Drug Info [16]
3-ethoxycarbonyl-4-quinolone Drug Info [17]
3-ethoxycarbonyl-6-ethyl-2-methyl-4-quinolone Drug Info [17]
3-ethoxycarbonyl-6-propyl-4-quinolone Drug Info [17]
3-Ethyl-3-isopropyl-dihydro-furan-2-one Drug Info [13]
3-Ethyl-3-methyl-dihydro-furan-2-one Drug Info [13]
3-Isopropyl-3-methyl-dihydro-furan-2-one Drug Info [13]
3-Isothiocyanato-9H-beta-carboline Drug Info [18]
3-Methyl-9H-beta-carboline Drug Info [19]
3-tert-Butyl-3-ethyl-dihydro-furan-2-one Drug Info [13]
4-(2-aminoethyl)-1,2,5-oxadiazol-3-ol Drug Info [20]
4-(4-chlorophenyl)-1-pyrid-2-yl-pyrazole Drug Info [14]
4-(biphenyl-3-yl)-5-(piperidin-4-yl)isoxazol-3-ol Drug Info [21]
4-Benzyl-5-piperidin-4-yl-isoxazol-3-ol Drug Info [22]
4-Naphthalen-1-yl-5-piperidin-4-yl-isoxazol-3-ol Drug Info [22]
4-Naphthalen-2-yl-5-piperidin-4-yl-isoxazol-3-ol Drug Info [22]
4-Phenyl-5-piperidin-4-yl-isoxazol-3-ol Drug Info [22]
5-(piperidin-4-yl)isoxazol-3-ol Drug Info [22]
5-[(1R)-1-ammonioethyl]isoxazol-3-olate Drug Info [11]
5-[(1S)-1-ammonioethyl]isoxazol-3-olate Drug Info [11]
6,6-Dimethyl-2-oxa-spiro[4.4]nonan-1-one Drug Info [13]
6,9-Dimethyl-2-oxa-spiro[4.4]nonan-1-one Drug Info [13]
6-benzyl-3-ethoxycarbonyl-4-quinolone Drug Info [17]
6-benzyl-3-propoxycarbonyl-4-quinolone Drug Info [17]
6-benzyl-3-propylaminocarbonyl-4-quinolone Drug Info [17]
6-bromo-3-ethoxycarbonyl-2-methyl-4-quinolone Drug Info [17]
6-bromo-3-ethoxycarbonyl-4-quinolone Drug Info [17]
6-ethyl-3-(2-ethylbutoxycarbonyl)-4-quinolone Drug Info [17]
6-ethyl-3-(2-methylbutoxycarbonyl)-4-quinolone Drug Info [17]
6-ethyl-3-(3-methylbutoxycarbonyl)-4-quinolone Drug Info [17]
6-ethyl-3-(3-pentoxycarbonyl)-4-quinolone Drug Info [17]
6-ethyl-3-i-propoxycarbonyl-4-quinolone Drug Info [17]
6-ethyl-3-pentoxycarbonyl-4-quinolone Drug Info [17]
6-ethyl-3-propoxycarbonyl-4-quinolone Drug Info [17]
6-ethyl-3-propylaminocarbonyl-4-quinolone Drug Info [17]
6-Methyl-2-oxa-spiro[4.4]nonan-1-one Drug Info [13]
ALLOPREGNANOLONE Drug Info [23]
AMENTOFLAVONE Drug Info [24]
BETA-CCM Drug Info [19]
CGS-13767 Drug Info [25]
CGS-8216 Drug Info [26]
CGS-9896 Drug Info [14]
CI-218872 Drug Info [19]
ELTANOLONE Drug Info [23]
GAMMA-AMINO-BUTANOIC ACID Drug Info [16]
GNF-PF-3645 Drug Info [17]
GNF-PF-4421 Drug Info [17]
N-(p-methylbenzyl)-5-nitroindol-3-ylglyoxylamide Drug Info [27]
N-Benzyl-2-(1H-indol-3-yl)-2-oxo-acetamide Drug Info [27]
N-benzyl-2-(5-nitro-1H-indol-3-yl)-2-oxoacetamide Drug Info [27]
N-butyl-2-(1H-indol-3-yl)-2-oxoacetamide Drug Info [27]
N-butyl-2-(5-nitro-1H-indol-3-yl)-2-oxoacetamide Drug Info [27]
N-Indan-1-yl-2-(1H-indol-3-yl)-2-oxo-acetamide Drug Info [28]
Ridine-5-carboxylic acid ethyl ester Drug Info [29]
RO-145974 Drug Info [30]
RO-145975 Drug Info [30]
RO-147437 Drug Info [30]
Ro-151310 Drug Info [30]
Ro-154513 Drug Info [30]
RO-194603 Drug Info [30]
THIOCOLCHICOSIDE Drug Info [16]
U-78875 Drug Info [31]
U-89267 Drug Info [32]
ZK-93423 Drug Info [33]
Antagonist Ethchlorvynol Drug Info [34]
Blocker (channel blocker) TBPS Drug Info [35]
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM)
TEP EXP Info
Pathways
KEGG Pathway Neuroactive ligand-receptor interaction
Retrograde endocannabinoid signaling
Serotonergic synapse
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 1FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (ANDA) 084463.
REF 2(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: 7180).
REF 3Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
REF 4(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: 4346).
REF 5Abecarnil enhances GABA-induced currents in acutely isolated cerebellar Purkinje cells. Neuropharmacology. 1995 Feb;34(2):157-63.
REF 6(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: 4108).
REF 7ClinicalTrials.gov (NCT01673828) Allopregnanolone for the Treatment of Traumatic Brain Injury. U.S. National Institutes of Health.
REF 8Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800005875)
REF 9Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800001194)
REF 10Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800000585)
REF 11J Med Chem. 1981 Dec;24(12):1377-83.gamma-Aminobutyric acid agonists, antagonists, and uptake inhibitors. Design and therapeutic aspects.
REF 12J Med Chem. 1989 May;32(5):1020-4.Benzodiazepine receptor binding activity of 6,9-disubstituted purines.
REF 13J Med Chem. 1994 Jan 21;37(2):275-86.Alpha-spirocyclopentyl- and alpha-spirocyclopropyl-gamma-butyrolactones: conformationally constrained derivatives of anticonvulsant and convulsant alpha,alpha-disubstituted gamma-butyrolactones.
REF 14J Med Chem. 2006 Mar 23;49(6):1855-66.Synthesis, pharmacology, and structure-activity relationships of novel imidazolones and pyrrolones as modulators of GABAA receptors.
REF 15J Med Chem. 1996 Jul 5;39(14):2844-51.Synthesis and structure--activity relationships of fused imidazopyridines: a new series of benzodiazepine receptor ligands.
REF 16J Med Chem. 2006 Sep 7;49(18):5571-7.3-demethoxy-3-glycosylaminothiocolchicines: Synthesis of a new class of putative muscle relaxant compounds.
REF 17J 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 18J Med Chem. 1990 Sep;33(9):2343-57.Synthetic and computer-assisted analyses of the pharmacophore for the benzodiazepine receptor inverse agonist site.
REF 19J Med Chem. 1994 Dec 23;37(26):4576-80.Four amino acid exchanges convert a diazepam-insensitive, inverse agonist-preferring GABAA receptor into a diazepam-preferring GABAA receptor.
REF 20J Med Chem. 2006 Jul 13;49(14):4442-6.Hydroxy-1,2,5-oxadiazolyl moiety as bioisoster of the carboxy function. Synthesis, ionization constants, and pharmacological characterization of gamma-aminobutyric acid (GABA) related compounds.
REF 21J Med Chem. 2010 Apr 22;53(8):3417-21.Novel 4-(piperidin-4-yl)-1-hydroxypyrazoles as gamma-aminobutyric acid(A) receptor ligands: synthesis, pharmacology, and structure-activity relationships.
REF 22J Med Chem. 2005 Jan 27;48(2):427-39.Potent 4-aryl- or 4-arylalkyl-substituted 3-isoxazolol GABA(A) antagonists: synthesis, pharmacology, and molecular modeling.
REF 23J Med Chem. 2005 Apr 21;48(8):3051-9.Neurosteroid analogues. 10. The effect of methyl group substitution at the C-6 and C-7 positions on the GABA modulatory and anesthetic actions of (3alpha,5alpha)-and (3alpha,5beta)-3-hydroxypregnan-20-one.
REF 24Bioorg Med Chem Lett. 2003 Jul 21;13(14):2281-4.Semisynthetic preparation of amentoflavone: A negative modulator at GABA(A) receptors.
REF 25J Med Chem. 1991 Jan;34(1):281-90.Synthesis and benzodiazepine binding activity of a series of novel [1,2,4]triazolo[1,5-c]quinazolin-5(6H)-ones.
REF 26Bioorg Med Chem Lett. 2000 Dec 18;10(24):2723-6.Substituted 3-(2-benzoxazyl)-benzimidazol-2-(1H)-ones: a new class of GABA(A) brain receptor ligands.
REF 27J Med Chem. 2007 Apr 5;50(7):1627-34. Epub 2007 Mar 3.Novel N-substituted indol-3-ylglyoxylamides probing the LDi and L1/L2 lipophilic regions of the benzodiazepine receptor site in search for subtype-selective ligands.
REF 28J Med Chem. 2001 Jul 5;44(14):2286-97.Novel N-(arylalkyl)indol-3-ylglyoxylylamides targeted as ligands of the benzodiazepine receptor: synthesis, biological evaluation, and molecular modeling analysis of the structure-activity relationships.
REF 29J Med Chem. 1989 Dec;32(12):2561-73.Synthesis and structure-activity relationships of a series of anxioselective pyrazolopyridine ester and amide anxiolytic agents.
REF 30J Med Chem. 1993 Apr 16;36(8):1001-6.Synthesis and evaluation of imidazo[1,5-a][1,4]benzodiazepine esters with high affinities and selectivities at "diazepam-insensitive" benzodiazepine receptors.
REF 31J Med Chem. 1996 Nov 8;39(23):4654-66.High-affinity alpha-aminobutyric acid A/benzodiazepine ligands: synthesis and structure-activity relationship studies of a new series of tetracyclic imidazoquinoxalines.
REF 32J Med Chem. 1994 Mar 18;37(6):758-68.Antagonist, partial agonist, and full agonist imidazo[1,5-a]quinoxaline amides and carbamates acting through the GABAA/benzodiazepine receptor.
REF 33J Med Chem. 1990 Mar;33(3):1062-9.Structural requirements for agonist actions at the benzodiazepine receptor: studies with analogues of 6-(benzyloxy)-4-(methoxymethyl)-beta-carboline-3-carboxylic acid ethyl ester.
REF 34DrugBank: a knowledgebase for drugs, drug actions and drug targets. Nucleic Acids Res. 2008 Jan;36(Database issue):D901-6. Epub 2007 Nov 29.
REF 35(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: 411).

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