Target Information
| Target General Information | Top | |||||
|---|---|---|---|---|---|---|
| Target ID |
T51487
(Former ID: TTDS00403)
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| Target Name |
GABA(A) receptor alpha-1 (GABRA1)
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| Synonyms |
Gamma-aminobutyric acid receptor subunit alpha-1; GABA(A) receptor subunit alpha-1
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| Gene Name |
GABRA1
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| Target Type |
Successful target
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[1] | ||||
| Disease | [+] 13 Target-related Diseases | + | ||||
| 1 | Acute respiratory distress syndrome [ICD-11: CB00] | |||||
| 2 | Anxiety disorder [ICD-11: 6B00-6B0Z] | |||||
| 3 | Chronic insomnia [ICD-11: 7A00] | |||||
| 4 | Chronic pain [ICD-11: MG30] | |||||
| 5 | Corneal disease [ICD-11: 9A76-9A78] | |||||
| 6 | Cystitis [ICD-11: GC00] | |||||
| 7 | Depression [ICD-11: 6A70-6A7Z] | |||||
| 8 | Epilepsy/seizure [ICD-11: 8A61-8A6Z] | |||||
| 9 | Headache [ICD-11: 8A80-8A84] | |||||
| 10 | Insomnia [ICD-11: 7A00-7A0Z] | |||||
| 11 | Malaria [ICD-11: 1F40-1F45] | |||||
| 12 | Mental/behavioural/neurodevelopmental disorder [ICD-11: 6E20-6E8Z] | |||||
| 13 | Tonus and reflex abnormality [ICD-11: MB47] | |||||
| Function |
Ligand-gated chloride channel which is a component of the heteropentameric receptor for GABA, the major inhibitory neurotransmitter in the brain. Plays an important role in the formation of functional inhibitory GABAergic synapses in addition to mediating synaptic inhibition as a GABA-gated ion channel. The gamma2 subunit is necessary but not sufficient for a rapid formation of active synaptic contacts and the synaptogenic effect of this subunit is influenced by the type of alpha and beta subunits present in the receptor pentamer (By similarity). The alpha1/beta2/gamma2 receptor and the alpha1/beta3/gamma2 receptor exhibit synaptogenic activity. GABRA1-mediated plasticity in the orbitofrontal cortex regulates context-dependent action selection (By similarity). Functions also as histamine receptor and mediates cellular responses to histamine (By similarity).
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| BioChemical Class |
Ligand-gated ion channel
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| UniProt ID | ||||||
| Sequence |
MRKSPGLSDCLWAWILLLSTLTGRSYGQPSLQDELKDNTTVFTRILDRLLDGYDNRLRPG
LGERVTEVKTDIFVTSFGPVSDHDMEYTIDVFFRQSWKDERLKFKGPMTVLRLNNLMASK IWTPDTFFHNGKKSVAHNMTMPNKLLRITEDGTLLYTMRLTVRAECPMHLEDFPMDAHAC PLKFGSYAYTRAEVVYEWTREPARSVVVAEDGSRLNQYDLLGQTVDSGIVQSSTGEYVVM TTHFHLKRKIGYFVIQTYLPCIMTVILSQVSFWLNRESVPARTVFGVTTVLTMTTLSISA RNSLPKVAYATAMDWFIAVCYAFVFSALIEFATVNYFTKRGYAWDGKSVVPEKPKKVKDP LIKKNNTYAPTATSYTPNLARGDPGLATIAKSATIEPKEVKPETKPPEPKKTFNSVSKID RLSRIAFPLLFGIFNLVYWATYLNREPQLKAPTPHQ Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
| HIT2.0 ID | T93QP3 | |||||
| Drugs and Modes of Action | Top | |||||
|---|---|---|---|---|---|---|
| Approved Drug(s) | [+] 25 Approved Drugs | + | ||||
| 1 | Allopregnanolone | Drug Info | Approved | Postpartum depression | [2], [3] | |
| 2 | Amobarbital | Drug Info | Approved | Insomnia | [4], [5] | |
| 3 | Barbital | Drug Info | Approved | Insomnia | [1] | |
| 4 | Barbiturate | Drug Info | Approved | Depression | [1] | |
| 5 | Butabarbital | Drug Info | Approved | Insomnia | [6], [7] | |
| 6 | Butalbital | Drug Info | Approved | Anxiety disorder | [5], [8], [9] | |
| 7 | Butethal | Drug Info | Approved | Insomnia | [10] | |
| 8 | Clobazam - Lundbeck | Drug Info | Approved | Anxiety disorder | [11], [12] | |
| 9 | Ethanol | Drug Info | Approved | Cystitis | [5], [13], [14] | |
| 10 | Ethchlorvynol | Drug Info | Approved | Insomnia | [15], [16] | |
| 11 | Hexobarbital | Drug Info | Approved | Anaesthesia | [17] | |
| 12 | Indiplon | Drug Info | Approved | Insomnia | [18], [19] | |
| 13 | Meprobamate | Drug Info | Approved | Malaria | [20], [5] | |
| 14 | Methohexital | Drug Info | Approved | Anaesthesia | [21], [22] | |
| 15 | Methoxyflurane | Drug Info | Approved | Anaesthesia | [23], [24] | |
| 16 | Methylphenobarbital | Drug Info | Approved | Anxiety disorder | [25] | |
| 17 | Methyprylon | Drug Info | Approved | Insomnia | [26], [27] | |
| 18 | Nitrazepam | Drug Info | Approved | Epilepsy | [28], [5] | |
| 19 | Pentobarbital | Drug Info | Approved | Insomnia | [5], [29], [30] | |
| 20 | Picrotoxin | Drug Info | Approved | Respiratory distress syndrome | [31], [32] | |
| 21 | Primidone | Drug Info | Approved | Epilepsy | [33], [34] | |
| 22 | Secobarbital | Drug Info | Approved | Intractable insomnia | [5] | |
| 23 | THIOCOLCHICOSIDE | Drug Info | Approved | Muscle spasm | [5] | |
| 24 | Zaleplon | Drug Info | Approved | Insomnia | [35], [36] | |
| 25 | Zolpidem | Drug Info | Approved | Insomnia | [37], [5] | |
| Clinical Trial Drug(s) | [+] 3 Clinical Trial Drugs | + | ||||
| 1 | ZK-93423 | Drug Info | Phase 3 | Epileptic seizures | [38], [39] | |
| 2 | EVT-201 | Drug Info | Phase 2 | Insomnia | [40] | |
| 3 | GSK683699 | Drug Info | Phase 2 | Inflammatory bowel disease | [41] | |
| Discontinued Drug(s) | [+] 2 Discontinued Drugs | + | ||||
| 1 | ELTANOLONE | Drug Info | Discontinued in Phase 3 | Premenstrual syndrome | [42] | |
| 2 | U-78875 | Drug Info | Discontinued in Phase 1 | Anxiety disorder | [43] | |
| Mode of Action | [+] 4 Modes of Action | + | ||||
| Inhibitor | [+] 169 Inhibitor drugs | + | ||||
| 1 | Allopregnanolone | Drug Info | [44] | |||
| 2 | THIOCOLCHICOSIDE | Drug Info | [48] | |||
| 3 | ZK-93423 | Drug Info | [51] | |||
| 4 | GSK683699 | Drug Info | [48] | |||
| 5 | ELTANOLONE | Drug Info | [44] | |||
| 6 | U-78875 | Drug Info | [52] | |||
| 7 | CGS-9896 | Drug Info | [53] | |||
| 8 | Divaplon | Drug Info | [54] | |||
| 9 | (2-Amino-4,5-dihydro-thiazol-4-yl)-acetic acid | Drug Info | [55] | |||
| 10 | (2E,4S)-4-ammoniopent-2-enoate | Drug Info | [56] | |||
| 11 | (4R)-4-ammoniopentanoate | Drug Info | [56] | |||
| 12 | (4S)-4-ammoniopentanoate | Drug Info | [56] | |||
| 13 | (6-Benzylamino-9H-beta-carbolin-3-yl)-methanol | Drug Info | [57] | |||
| 14 | (9-Benzyl-9H-purin-6-yl)-cyclopropyl-amine | Drug Info | [58] | |||
| 15 | (9H-beta-Carbolin-3-yl)-carbamic acid ethyl ester | Drug Info | [59] | |||
| 16 | (9H-beta-Carbolin-3-yl)-ethyl-amine | Drug Info | [59] | |||
| 17 | (9H-beta-Carbolin-3-yl)-methanol | Drug Info | [57] | |||
| 18 | (beta-CCE)9H-beta-Carboline-3-carboxylic acid | Drug Info | [60] | |||
| 19 | 1,1-Dimethyl-5-oxa-spiro[2.4]heptan-4-one | Drug Info | [61] | |||
| 20 | 1,3-Diphenyl-1H-chromeno[4,3-c]pyrazol-4-one | Drug Info | [62] | |||
| 21 | 1-(4-chlorophenyl)-4-phenyl-1H-imidazole | Drug Info | [53] | |||
| 22 | 1-(9H-beta-Carbolin-3-yl)-butan-1-one | Drug Info | [63] | |||
| 23 | 1-(9H-beta-Carbolin-3-yl)-ethanone | Drug Info | [57] | |||
| 24 | 1-Methyl-5-oxa-spiro[2.4]heptan-4-one | Drug Info | [61] | |||
| 25 | 2-(1H-Indol-3-yl)-2-oxo-N-phenethyl-acetamide | Drug Info | [60] | |||
| 26 | 2-(3-Bromo-phenyl)-6-nitro-chromen-4-one | Drug Info | [64] | |||
| 27 | 2-(3-Bromo-phenyl)-chromen-4-one | Drug Info | [64] | |||
| 28 | 2-(3-Chloro-phenyl)-chromen-4-one | Drug Info | [64] | |||
| 29 | 2-(4-Chloro-phenyl)-3H-imidazo[4,5-c]quinoline | Drug Info | [65] | |||
| 30 | 2-(4-chlorophenyl)-5-phenyl-4-isoxazolin-3-one | Drug Info | [53] | |||
| 31 | 2-(9-Benzyl-9H-purin-6-ylamino)-ethanol | Drug Info | [58] | |||
| 32 | 2-Furan-2-yl-6H-pyrazolo[1,5-c]quinazolin-5-one | Drug Info | [66] | |||
| 33 | 2-Isoxazol-3-yl-3H-imidazo[4,5-c]quinoline | Drug Info | [65] | |||
| 34 | 2-Isoxazol-5-yl-3H-imidazo[4,5-c]quinoline | Drug Info | [65] | |||
| 35 | 2-Oxa-spiro[4.4]nonan-1-one | Drug Info | [61] | |||
| 36 | 2-p-Tolyl-6H-pyrazolo[1,5-c]quinazolin-5-one | Drug Info | [66] | |||
| 37 | 2-Phenyl-3H-imidazo[4,5-c]quinoline | Drug Info | [65] | |||
| 38 | 2-Phenyl-5,6-dihydro-pyrazolo[1,5-c]quinazoline | Drug Info | [66] | |||
| 39 | 2-Phenyl-6H-pyrazolo[1,5-c]quinazolin-5-one | Drug Info | [66] | |||
| 40 | 2-Pyridin-2-yl-6H-pyrazolo[1,5-c]quinazolin-5-one | Drug Info | [66] | |||
| 41 | 2-Thiophen-2-yl-3H-imidazo[4,5-c]quinoline | Drug Info | [65] | |||
| 42 | 3,3-Diethyl-dihydro-furan-2-one | Drug Info | [61] | |||
| 43 | 3,3-Diisopropyl-dihydro-furan-2-one | Drug Info | [61] | |||
| 44 | 3-(2,2-Dimethyl-propoxy)-9H-beta-carboline | Drug Info | [63] | |||
| 45 | 3-(3-Methyl-butoxy)-9H-beta-carboline | Drug Info | [63], [67] | |||
| 46 | 3-(benzyloxy)-9H-pyrido[3,4-b]indole | Drug Info | [67] | |||
| 47 | 3-(hexa-1,3-dienyloxy)-9H-pyrido[3,4-b]indole | Drug Info | [67] | |||
| 48 | 3-amino-3-demethoxythiocolchicine | Drug Info | [48] | |||
| 49 | 3-Butoxy-9H-beta-carboline | Drug Info | [63], [67] | |||
| 50 | 3-butoxycarbonyl-4-quinolone | Drug Info | [68] | |||
| 51 | 3-butoxycarbonyl-6-ethyl-4-quinolone | Drug Info | [68] | |||
| 52 | 3-butylaminocarbonyl-6-ethyl-4-quinolone | Drug Info | [68] | |||
| 53 | 3-carboxy-6-ethyl-4-quinolone | Drug Info | [68] | |||
| 54 | 3-Chloro-9H-beta-carboline | Drug Info | [69] | |||
| 55 | 3-cyclopentoxycarbonyl-6-ethyl-4-quinolone | Drug Info | [68] | |||
| 56 | 3-demethoxy-3-D-lyxopyranosylaminothiocolchicine | Drug Info | [48] | |||
| 57 | 3-demethoxy-3-D-mannopyranosylaminothiocolchicine | Drug Info | [48] | |||
| 58 | 3-demethoxy-3-D-xylopyranosylaminothiocolchicine | Drug Info | [48] | |||
| 59 | 3-demethoxy-3-L-fucopyranosylaminothiocolchicine | Drug Info | [48] | |||
| 60 | 3-demethoxy-3D-glucopyranosylaminothiocolchicine | Drug Info | [48] | |||
| 61 | 3-Ethoxy-9H-beta-carboline | Drug Info | [69], [67] | |||
| 62 | 3-ethoxycarbonyl-4-quinolone | Drug Info | [68] | |||
| 63 | 3-ethoxycarbonyl-6-ethyl-2-methyl-4-quinolone | Drug Info | [68] | |||
| 64 | 3-ethoxycarbonyl-6-propyl-4-quinolone | Drug Info | [68] | |||
| 65 | 3-Ethyl-3-isopropyl-dihydro-furan-2-one | Drug Info | [61] | |||
| 66 | 3-Ethyl-3-methyl-dihydro-furan-2-one | Drug Info | [61] | |||
| 67 | 3-Isobutoxy-9H-beta-carboline | Drug Info | [63], [67] | |||
| 68 | 3-Isopropoxy-9H-beta-carboline | Drug Info | [63] | |||
| 69 | 3-Isopropyl-3-methyl-dihydro-furan-2-one | Drug Info | [61] | |||
| 70 | 3-Isothiocyanato-9H-beta-carboline | Drug Info | [70] | |||
| 71 | 3-Methoxy-9H-beta-carboline | Drug Info | [69] | |||
| 72 | 3-Methoxycarbonyl-2-methyl-9H-beta-carbolin-2-ium | Drug Info | [71] | |||
| 73 | 3-Methyl-1-phenyl-1H-chromeno[4,3-c]pyrazol-4-one | Drug Info | [62] | |||
| 74 | 3-Methyl-2-phenyl-2H-chromeno[4,3-c]pyrazol-4-one | Drug Info | [62] | |||
| 75 | 3-Methyl-9H-beta-carboline | Drug Info | [72] | |||
| 76 | 3-Nitro-9H-beta-carboline | Drug Info | [69] | |||
| 77 | 3-Propoxy-9H-beta-carboline | Drug Info | [69], [67] | |||
| 78 | 3-sec-Butoxy-9H-beta-carboline | Drug Info | [63] | |||
| 79 | 3-tert-Butyl-3-ethyl-dihydro-furan-2-one | Drug Info | [61] | |||
| 80 | 4-(2-aminoethyl)-1,2,5-oxadiazol-3-ol | Drug Info | [73] | |||
| 81 | 4-(4-chlorophenyl)-1-pyrid-2-yl-pyrazole | Drug Info | [53] | |||
| 82 | 4-(biphenyl-3-yl)-5-(piperidin-4-yl)isoxazol-3-ol | Drug Info | [74] | |||
| 83 | 4-benzyl-5-(4-piperidyl)isothiazol-3-ol | Drug Info | [75] | |||
| 84 | 4-Benzyl-5-piperidin-4-yl-isoxazol-3-ol | Drug Info | [76] | |||
| 85 | 4-Methoxymethyl-3,6-dipropoxy-9H-beta-carboline | Drug Info | [77] | |||
| 86 | 4-Methyl-5-(4-piperidyl)isothiazol-3-ol | Drug Info | [75] | |||
| 87 | 4-Naphthalen-1-yl-5-piperidin-4-yl-isoxazol-3-ol | Drug Info | [76] | |||
| 88 | 4-Naphthalen-2-yl-5-piperidin-4-yl-isoxazol-3-ol | Drug Info | [76] | |||
| 89 | 4-Phenyl-5-piperidin-4-yl-isoxazol-3-ol | Drug Info | [76] | |||
| 90 | 5-(4-piperidyl)-4-propylisothiazol-3-ol | Drug Info | [75] | |||
| 91 | 5-(piperidin-4-yl)isothiazol-3-ol | Drug Info | [75] | |||
| 92 | 5-(piperidin-4-yl)isoxazol-3-ol | Drug Info | [76] | |||
| 93 | 5-[(1R)-1-ammonioethyl]isoxazol-3-olate | Drug Info | [56] | |||
| 94 | 5-[(1S)-1-ammonioethyl]isoxazol-3-olate | Drug Info | [56] | |||
| 95 | 6,6-Dimethyl-2-oxa-spiro[4.4]nonan-1-one | Drug Info | [61] | |||
| 96 | 6,9-Dimethyl-2-oxa-spiro[4.4]nonan-1-one | Drug Info | [61] | |||
| 97 | 6-benzyl-3-ethoxycarbonyl-4-quinolone | Drug Info | [68] | |||
| 98 | 6-benzyl-3-propoxycarbonyl-4-quinolone | Drug Info | [68] | |||
| 99 | 6-benzyl-3-propylaminocarbonyl-4-quinolone | Drug Info | [68] | |||
| 100 | 6-Bromo-2-(2-nitro-phenyl)-chromen-4-one | Drug Info | [78] | |||
| 101 | 6-Bromo-2-(3-bromo-phenyl)-chromen-4-one | Drug Info | [64] | |||
| 102 | 6-Bromo-2-(3-nitro-phenyl)-chromen-4-one | Drug Info | [78] | |||
| 103 | 6-Bromo-2-(4-nitro-phenyl)-chromen-4-one | Drug Info | [78] | |||
| 104 | 6-Bromo-2-phenyl-chromen-4-one | Drug Info | [64] | |||
| 105 | 6-bromo-3-ethoxycarbonyl-2-methyl-4-quinolone | Drug Info | [68] | |||
| 106 | 6-bromo-3-ethoxycarbonyl-4-quinolone | Drug Info | [68] | |||
| 107 | 6-Chloro-2-(3-nitro-phenyl)-chromen-4-one | Drug Info | [64] | |||
| 108 | 6-Chloro-2-phenyl-chromen-4-one | Drug Info | [64] | |||
| 109 | 6-ethyl-3-(2-ethylbutoxycarbonyl)-4-quinolone | Drug Info | [68] | |||
| 110 | 6-ethyl-3-(2-methylbutoxycarbonyl)-4-quinolone | Drug Info | [68] | |||
| 111 | 6-ethyl-3-(3-methylbutoxycarbonyl)-4-quinolone | Drug Info | [68] | |||
| 112 | 6-ethyl-3-(3-pentoxycarbonyl)-4-quinolone | Drug Info | [68] | |||
| 113 | 6-ethyl-3-i-propoxycarbonyl-4-quinolone | Drug Info | [68] | |||
| 114 | 6-ethyl-3-pentoxycarbonyl-4-quinolone | Drug Info | [68] | |||
| 115 | 6-ethyl-3-propoxycarbonyl-4-quinolone | Drug Info | [68] | |||
| 116 | 6-ethyl-3-propylaminocarbonyl-4-quinolone | Drug Info | [68] | |||
| 117 | 6-Fluoro-2-(3-nitro-phenyl)-chromen-4-one | Drug Info | [64] | |||
| 118 | 6-Methyl-2-oxa-spiro[4.4]nonan-1-one | Drug Info | [61] | |||
| 119 | 6-Nitro-2-(3-nitro-phenyl)-chromen-4-one | Drug Info | [79] | |||
| 120 | 6-Nitro-2-(4-nitro-phenyl)-chromen-4-one | Drug Info | [79] | |||
| 121 | 6-Nitro-2-phenyl-chromen-4-one | Drug Info | [64] | |||
| 122 | 7,12-Dihydro-5,7,12-triaza-indeno[1,2-a]fluorene | Drug Info | [80] | |||
| 123 | 7,12-Dihydro-7,12-diaza-indeno[1,2-a]fluorene | Drug Info | [69] | |||
| 124 | 9H-beta-Carbolin-3-ol | Drug Info | [69] | |||
| 125 | 9H-beta-Carbolin-6-ylamine | Drug Info | [57] | |||
| 126 | 9H-beta-Carboline-3-carboxylic acid ethyl ester | Drug Info | [67], [81] | |||
| 127 | 9H-beta-Carboline-3-carboxylic acid propyl ester | Drug Info | [81] | |||
| 128 | AMENTOFLAVONE | Drug Info | [82] | |||
| 129 | Barbituric acid derivative | Drug Info | [83] | |||
| 130 | Benzyl-(9H-beta-carbolin-6-yl)-amine | Drug Info | [69] | |||
| 131 | Beta-Carboline-3-carboxylic acid t-butyl ester | Drug Info | [67] | |||
| 132 | BETA-CCM | Drug Info | [84] | |||
| 133 | CGS-13767 | Drug Info | [85] | |||
| 134 | CGS-9895 | Drug Info | [86] | |||
| 135 | CI-218872 | Drug Info | [72] | |||
| 136 | Ethyl 6-iodo-9H-pyrido[3,4-b]indole-3-carboxylate | Drug Info | [67] | |||
| 137 | flavone | Drug Info | [64] | |||
| 138 | GNF-PF-3645 | Drug Info | [68] | |||
| 139 | GNF-PF-4421 | Drug Info | [68] | |||
| 140 | Isoquinoline-3-carboxylic acid methyl ester | Drug Info | [69] | |||
| 141 | L-655708 | Drug Info | [87] | |||
| 142 | N-(9H-beta-Carbolin-3-yl)-acetamide | Drug Info | [59] | |||
| 143 | N-(9H-beta-Carbolin-3-yl)-formamide | Drug Info | [59] | |||
| 144 | N-(p-methylbenzyl)-5-nitroindol-3-ylglyoxylamide | Drug Info | [88] | |||
| 145 | N-Benzyl-2-(1H-indol-3-yl)-2-oxo-acetamide | Drug Info | [88] | |||
| 146 | N-benzyl-2-(5-nitro-1H-indol-3-yl)-2-oxoacetamide | Drug Info | [88] | |||
| 147 | N-butyl-2-(1H-indol-3-yl)-2-oxoacetamide | Drug Info | [88] | |||
| 148 | N-butyl-2-(5-nitro-1H-indol-3-yl)-2-oxoacetamide | Drug Info | [88] | |||
| 149 | N-Indan-1-yl-2-(1H-indol-3-yl)-2-oxo-acetamide | Drug Info | [89] | |||
| 150 | NORHARMANE | Drug Info | [69] | |||
| 151 | NSC-73613 | Drug Info | [64] | |||
| 152 | NSC-93394 | Drug Info | [64] | |||
| 153 | Pyrrolidin-3-yl-acetic acid | Drug Info | [90] | |||
| 154 | Ridine-5-carboxylic acid ethyl ester | Drug Info | [91] | |||
| 155 | RIPAZEPAM | Drug Info | [92] | |||
| 156 | RO-054520 | Drug Info | [93] | |||
| 157 | RO-145974 | Drug Info | [94] | |||
| 158 | RO-145975 | Drug Info | [94] | |||
| 159 | RO-147437 | Drug Info | [94] | |||
| 160 | Ro-15-3505 | Drug Info | [94] | |||
| 161 | RO-194603 | Drug Info | [94] | |||
| 162 | Ro-4938581 | Drug Info | [95] | |||
| 163 | RWJ-16979 | Drug Info | [96] | |||
| 164 | RY-066 | Drug Info | [97] | |||
| 165 | Sec-butyl 9H-pyrido[3,4-b]indole-3-carboxylate | Drug Info | [67] | |||
| 166 | U-89267 | Drug Info | [98] | |||
| 167 | [3H]CGP27492 | Drug Info | [99] | |||
| 168 | [3H]CGS8216 | Drug Info | [85] | |||
| 169 | [3H]Ro154513 | Drug Info | [94] | |||
| Antagonist | [+] 20 Antagonist drugs | + | ||||
| 1 | Amobarbital | Drug Info | [1], [45] | |||
| 2 | Barbital | Drug Info | [1], [45] | |||
| 3 | Barbiturate | Drug Info | [1], [45] | |||
| 4 | Butabarbital | Drug Info | [1], [45], [46] | |||
| 5 | Butalbital | Drug Info | [1] | |||
| 6 | Butethal | Drug Info | [1] | |||
| 7 | Clobazam - Lundbeck | Drug Info | [1] | |||
| 8 | Ethanol | Drug Info | [1] | |||
| 9 | Ethchlorvynol | Drug Info | [1] | |||
| 10 | Hexobarbital | Drug Info | [1], [45] | |||
| 11 | Meprobamate | Drug Info | [1] | |||
| 12 | Methohexital | Drug Info | [1] | |||
| 13 | Methoxyflurane | Drug Info | [1] | |||
| 14 | Methylphenobarbital | Drug Info | [1], [45] | |||
| 15 | Methyprylon | Drug Info | [1] | |||
| 16 | Nitrazepam | Drug Info | [1] | |||
| 17 | Pentobarbital | Drug Info | [1], [45] | |||
| 18 | Picrotoxin | Drug Info | [1] | |||
| 19 | Primidone | Drug Info | [1] | |||
| 20 | Secobarbital | Drug Info | [1], [45] | |||
| Agonist | [+] 1 Agonist drugs | + | ||||
| 1 | Indiplon | Drug Info | [19], [47] | |||
| Modulator | [+] 3 Modulator drugs | + | ||||
| 1 | Zaleplon | Drug Info | [49] | |||
| 2 | Zolpidem | Drug Info | [50] | |||
| 3 | EVT-201 | Drug Info | [2] | |||
| Cell-based Target Expression Variations | Top | |||||
|---|---|---|---|---|---|---|
| Cell-based Target Expression Variations | ||||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| Ligand Name: Propofol | Ligand Info | |||||
| Structure Description | Human GABAA receptor alpha1-beta2-gamma2 subtype in complex with GABA plus propofol | PDB:6X3T | ||||
| Method | Electron microscopy | Resolution | 2.55 Å | Mutation | No | [100] |
| PDB Sequence |
DNTTVFTRIL
19 DRLLDGYDNR29 LRPGLGERVT39 EVKTDIFVTS49 FGPVSDHDME59 YTIDVFFRQS 69 WKDERLKFKG79 PMTVLRLNNL89 MASKIWTPDT99 FFHNGKKSVA109 HNMTMPNKLL 119 RITEDGTLLY129 TMRLTVRAEC139 PMHLEDFPMD149 AHACPLKFGS159 YAYTRAEVVY 169 EWTREPARSV179 VVAEDGSRLN189 QYDLLGQTVD199 SGIVQSSTGE209 YVVMTTHFHL 219 KRKIGYFVIQ229 TYLPCIMTVI239 LSQVSFWLNR249 ESVPARTVFG259 VTTVLTMTTL 269 SISARNSLPK279 VAYATAMDWF289 IAVCYAFVFS299 ALIEFATVNY309 FTKSQPARAA 319 KIDRLSRIAF329 PLLFGIFNLV339 YWATYLNR
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| Ligand Name: Zolpidem | Ligand Info | |||||
| Structure Description | Human GABAA receptor alpha1-beta2-gamma2 subtype in complex with GABA plus Zolpidem | PDB:8DD2 | ||||
| Method | Electron microscopy | Resolution | 2.90 Å | Mutation | No | [101] |
| PDB Sequence |
DNTTVFTRIL
19 DRLLDGYDNR29 LRPGLGERVT39 EVKTDIFVTS49 FGPVSDHDME59 YTIDVFFRQS 69 WKDERLKFKG79 PMTVLRLNNL89 MASKIWTPDT99 FFHNGKKSVA109 HNMTMPNKLL 119 RITEDGTLLY129 TMRLTVRAEC139 PMHLEDFPMD149 AHACPLKFGS159 YAYTRAEVVY 169 EWTREPARSV179 VVAEDGSRLN189 QYDLLGQTVD199 SGIVQSSTGE209 YVVMTTHFHL 219 KRKIGYFVIQ229 TYLPCIMTVI239 LSQVSFWLNR249 ESVPARTVFG259 VTTVLTMTTL 269 SISARNSLPK279 VAYATAMDWF289 IAVCYAFVFS299 ALIEFATVNY309 FTKSQPARAA 319 KIDRLSRIAF329 PLLFGIFNLV339 YWATYLNR
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| Click to View More Binding Site Information of This Target with Different Ligands | ||||||
| Different Human System Profiles of Target | Top |
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Human Similarity Proteins
of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.
A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs
(Brief Bioinform, 21: 649-662, 2020).
Human Tissue Distribution
of target is determined from a proteomics study that quantified more than 12,000 genes across 32 normal human tissues. Tissue Specificity (TS) score was used to define the enrichment of target across tissues.
The distribution of targets among different tissues or organs need to be taken into consideration when assessing the target druggability, as it is generally accepted that the wider the target distribution, the greater the concern over potential adverse effects
(Nat Rev Drug Discov, 20: 64-81, 2021).
Human Pathway Affiliation
of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function.
Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes
(Pharmacol Rev, 58: 259-279, 2006).
Biological Network Descriptors
of target is determined based on a human protein-protein interactions (PPI) network consisting of 9,309 proteins and 52,713 PPIs, which were with a high confidence score of ≥ 0.95 collected from STRING database.
The network properties of targets based on protein-protein interactions (PPIs) have been widely adopted for the assessment of target’s druggability. Proteins with high node degree tend to have a high impact on network function through multiple interactions, while proteins with high betweenness centrality are regarded to be central for communication in interaction networks and regulate the flow of signaling information
(Front Pharmacol, 9, 1245, 2018;
Curr Opin Struct Biol. 44:134-142, 2017).
Human Similarity Proteins
Human Tissue Distribution
Human Pathway Affiliation
Biological Network Descriptors
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There is no similarity protein (E value < 0.005) for this target
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Note:
If a protein has TS (tissue specficity) scores at least in one tissue >= 2.5, this protein is called tissue-enriched (including tissue-enriched-but-not-specific and tissue-specific). In the plots, the vertical lines are at thresholds 2.5 and 4.
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| KEGG Pathway | Pathway ID | Affiliated Target | Pathway Map |
|---|---|---|---|
| Neuroactive ligand-receptor interaction | hsa04080 | Affiliated Target |
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| Class: Environmental Information Processing => Signaling molecules and interaction | Pathway Hierarchy | ||
| Retrograde endocannabinoid signaling | hsa04723 | Affiliated Target |
|
| Class: Organismal Systems => Nervous system | Pathway Hierarchy | ||
| GABAergic synapse | hsa04727 | Affiliated Target |
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| Class: Organismal Systems => Nervous system | Pathway Hierarchy | ||
| Taste transduction | hsa04742 | Affiliated Target |
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| Class: Organismal Systems => Sensory system | Pathway Hierarchy | ||
| Degree | 5 | Degree centrality | 5.37E-04 | Betweenness centrality | 8.10E-04 |
|---|---|---|---|---|---|
| Closeness centrality | 1.72E-01 | Radiality | 1.27E+01 | Clustering coefficient | 0.00E+00 |
| Neighborhood connectivity | 2.80E+00 | Topological coefficient | 2.00E-01 | Eccentricity | 13 |
| Download | Click to Download the Full PPI Network of This Target | ||||
| Chemical Structure based Activity Landscape of Target | Top |
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| Drug Property Profile of Target | Top | |
|---|---|---|
| (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 | ||
| Co-Targets | Top | |||||
|---|---|---|---|---|---|---|
| Co-Targets | ||||||
| Target Poor or Non Binders | Top | |||||
|---|---|---|---|---|---|---|
| Target Poor or Non Binders | ||||||
| Target Profiles in Patients | Top | |||||
|---|---|---|---|---|---|---|
| Target Expression Profile (TEP) | ||||||
| Target Affiliated Biological Pathways | Top | |||||
|---|---|---|---|---|---|---|
| KEGG Pathway | [+] 5 KEGG Pathways | + | ||||
| 1 | Neuroactive ligand-receptor interaction | |||||
| 2 | Retrograde endocannabinoid signaling | |||||
| 3 | GABAergic synapse | |||||
| 4 | Morphine addiction | |||||
| 5 | Nicotine addiction | |||||
| Reactome | [+] 2 Reactome Pathways | + | ||||
| 1 | Ligand-gated ion channel transport | |||||
| 2 | GABA A receptor activation | |||||
| WikiPathways | [+] 3 WikiPathways | + | ||||
| 1 | SIDS Susceptibility Pathways | |||||
| 2 | Neurotransmitter Receptor Binding And Downstream Transmission In The Postsynaptic Cell | |||||
| 3 | Iron uptake and transport | |||||
| Target-Related Models and Studies | Top | |||||
|---|---|---|---|---|---|---|
| Target Validation | ||||||
| References | Top | |||||
|---|---|---|---|---|---|---|
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