Target Information
| Target General Information | Top | |||||
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| Target ID |
T64765
(Former ID: TTDC00079)
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| Target Name |
Histamine H3 receptor (H3R)
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| Synonyms |
Histamine receptor 3; HH3R; GPCR97; G-protein coupled receptor 97; G protein-coupled receptor 97
Click to Show/Hide
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| Gene Name |
HRH3
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| Target Type |
Successful target
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[1] | ||||
| Disease | [+] 1 Target-related Diseases | + | ||||
| 1 | Somnolence [ICD-11: MG42] | |||||
| Function |
Signals through the inhibition of adenylate cyclase and displays high constitutive activity (spontaneous activity in the absence of agonist). Agonist stimulation of isoform 3 neither modified adenylate cyclase activity nor induced intracellular calcium mobilization. The H3 subclass of histamine receptors could mediate the histamine signals in CNS and peripheral nervous system.
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| BioChemical Class |
GPCR rhodopsin
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| UniProt ID | ||||||
| Sequence |
MERAPPDGPLNASGALAGEAAAAGGARGFSAAWTAVLAALMALLIVATVLGNALVMLAFV
ADSSLRTQNNFFLLNLAISDFLVGAFCIPLYVPYVLTGRWTFGRGLCKLWLVVDYLLCTS SAFNIVLISYDRFLSVTRAVSYRAQQGDTRRAVRKMLLVWVLAFLLYGPAILSWEYLSGG SSIPEGHCYAEFFYNWYFLITASTLEFFTPFLSVTFFNLSIYLNIQRRTRLRLDGAREAA GPEPPPEAQPSPPPPPGCWGCWQKGHGEAMPLHRYGVGEAAVGAEAGEATLGGGGGGGSV ASPTSSSGSSSRGTERPRSLKRGSKPSASSASLEKRMKMVSQSFTQRFRLSRDRKVAKSL AVIVSIFGLCWAPYTLLMIIRAACHGHCVPDYWYETSFWLLWANSAVNPVLYPLCHHSFR RAFTKLLCPQKLKIQPHSSLEHCWK Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | AlphaFold | ||||
| HIT2.0 ID | T88AHJ | |||||
| Drugs and Modes of Action | Top | |||||
|---|---|---|---|---|---|---|
| Approved Drug(s) | [+] 1 Approved Drugs | + | ||||
| 1 | Pitolisant | Drug Info | Approved | Excessive daytime sleepiness | [2] | |
| Clinical Trial Drug(s) | [+] 16 Clinical Trial Drugs | + | ||||
| 1 | SUVN-G3031 | Drug Info | Phase 3 | Cognitive impairment | [3], [4] | |
| 2 | ABT-288 | Drug Info | Phase 2 | Alzheimer disease | [6], [7] | |
| 3 | ABT-652 | Drug Info | Phase 2 | Musculoskeletal pain | [8] | |
| 4 | AZD-5213 | Drug Info | Phase 2 | Alzheimer disease | [9] | |
| 5 | Bavisant | Drug Info | Phase 2 | Attention deficit hyperactivity disorder | [10] | |
| 6 | GSK239512 | Drug Info | Phase 2 | Dementia | [11] | |
| 7 | JNJ-17216498 | Drug Info | Phase 2 | Narcolepsy | [12] | |
| 8 | JNJ-39220675 | Drug Info | Phase 2 | Alcohol dependence | [13] | |
| 9 | SAR-110894 | Drug Info | Phase 2 | Alzheimer disease | [14] | |
| 10 | ABT-239 | Drug Info | Phase 1 | Cognitive impairment | [15], [16] | |
| 11 | APD-916 | Drug Info | Phase 1 | Sleep-wake disorder | [17] | |
| 12 | HPP404 | Drug Info | Phase 1 | Allergic rhinitis | [18] | |
| 13 | Irdabisant | Drug Info | Phase 1 | Cognitive impairment | [19] | |
| 14 | MK-3134 | Drug Info | Phase 1 | Dementia | [20] | |
| 15 | MK-7288 | Drug Info | Phase 1 | Excessive daytime sleepiness | [21] | |
| 16 | MK-0249 | Drug Info | Clinical trial | Insulin-resistant disorder | [22] | |
| Patented Agent(s) | [+] 7 Patented Agents | + | ||||
| 1 | Biphenyl derivative 4 | Drug Info | Patented | Histamine H3-associated disorder | [23] | |
| 2 | Phenylsulfonyl derivative 2 | Drug Info | Patented | Central nervous system disease | [23] | |
| 3 | Phenylsulfonyl derivative 3 | Drug Info | Patented | Central nervous system disease | [23] | |
| 4 | PMID29334795-Compound-21 | Drug Info | Patented | Progressive supranuclear palsy | [23] | |
| 5 | PMID29334795-Compound-22 | Drug Info | Patented | Neuropathic pain | [23] | |
| 6 | PMID29334795-Compound-23 | Drug Info | Patented | Schizophrenia | [23] | |
| 7 | PMID29334795-Compound-28 | Drug Info | Patented | Histamine H3-associated disorder | [23] | |
| Discontinued Drug(s) | [+] 9 Discontinued Drugs | + | ||||
| 1 | BP-2.94 | Drug Info | Discontinued in Phase 2 | Pain | [24] | |
| 2 | Cipralisant | Drug Info | Discontinued in Phase 2 | Attention deficit hyperactivity disorder | [25], [26] | |
| 3 | GSK835726 | Drug Info | Discontinued in Phase 2 | Allergic rhinitis | [27] | |
| 4 | GSK1004723 | Drug Info | Discontinued in Phase 1 | Allergic rhinitis | [28] | |
| 5 | SAR-152954 | Drug Info | Discontinued in Phase 1 | Sleep-wake disorder | [29] | |
| 6 | GT-2016 | Drug Info | Terminated | Alzheimer disease | [30] | |
| 7 | GT-2203 | Drug Info | Terminated | Anxiety disorder | [31] | |
| 8 | Thioperamide | Drug Info | Terminated | Cognitive impairment | [32], [33] | |
| 9 | UCL-1390 | Drug Info | Terminated | Pain | [34] | |
| Mode of Action | [+] 8 Modes of Action | + | ||||
| Agonist | [+] 19 Agonist drugs | + | ||||
| 1 | Pitolisant | Drug Info | [2] | |||
| 2 | MK-3134 | Drug Info | [46] | |||
| 3 | MK-7288 | Drug Info | [47] | |||
| 4 | MK-0249 | Drug Info | [48] | |||
| 5 | GT-2203 | Drug Info | [53] | |||
| 6 | (R)-alpha-methylhistamine | Drug Info | [16], [60], [61] | |||
| 7 | (S)-alpha-methylhistamine | Drug Info | [62] | |||
| 8 | imbutamine | Drug Info | [84] | |||
| 9 | Imetit | Drug Info | [16] | |||
| 10 | Immepip | Drug Info | [16] | |||
| 11 | Immethridine | Drug Info | [16] | |||
| 12 | impentamine | Drug Info | [84] | |||
| 13 | impromidine | Drug Info | [61] | |||
| 14 | Methimepip | Drug Info | [16] | |||
| 15 | N-methylhistamine | Drug Info | [61] | |||
| 16 | N-[3H]alpha-methylhistamine | Drug Info | [87] | |||
| 17 | N-[3H]methylhistamine | Drug Info | [61] | |||
| 18 | VUF 5207 | Drug Info | [88] | |||
| 19 | VUF 8328 | Drug Info | [88] | |||
| Antagonist | [+] 41 Antagonist drugs | + | ||||
| 1 | SUVN-G3031 | Drug Info | [3], [4] | |||
| 2 | AZD-5213 | Drug Info | [37] | |||
| 3 | Bavisant | Drug Info | [38] | |||
| 4 | GSK239512 | Drug Info | [39] | |||
| 5 | JNJ-17216498 | Drug Info | [40] | |||
| 6 | JNJ-39220675 | Drug Info | [41] | |||
| 7 | SAR-110894 | Drug Info | [37] | |||
| 8 | ABT-239 | Drug Info | [16], [42], [43] | |||
| 9 | APD-916 | Drug Info | [44] | |||
| 10 | HPP404 | Drug Info | [18] | |||
| 11 | Irdabisant | Drug Info | [45] | |||
| 12 | GSK835726 | Drug Info | [39] | |||
| 13 | GSK1004723 | Drug Info | [39] | |||
| 14 | SAR-152954 | Drug Info | [51] | |||
| 15 | Thioperamide | Drug Info | [16], [54] | |||
| 16 | UCL-1390 | Drug Info | [26] | |||
| 17 | A-304121 | Drug Info | [78] | |||
| 18 | A-317920 | Drug Info | [16] | |||
| 19 | A-331440 | Drug Info | [16] | |||
| 20 | burimamide | Drug Info | [61] | |||
| 21 | Ciproxifan | Drug Info | [16] | |||
| 22 | Clobenpropit | Drug Info | [16], [54] | |||
| 23 | EVT-501 | Drug Info | [53] | |||
| 24 | FUB 349 | Drug Info | [83], [74] | |||
| 25 | FUB-130 | Drug Info | [53] | |||
| 26 | GSK-334429 | Drug Info | [53] | |||
| 27 | GSK189254A | Drug Info | [16] | |||
| 28 | GT2394 | Drug Info | [62] | |||
| 29 | JB 98064 | Drug Info | [62] | |||
| 30 | JNJ-5207852 | Drug Info | [16] | |||
| 31 | PF-3900422 | Drug Info | [53] | |||
| 32 | Proxyfan | Drug Info | [16] | |||
| 33 | SCH79687 | Drug Info | [16] | |||
| 34 | SUVN-G1031 | Drug Info | [53] | |||
| 35 | UCB-2892 | Drug Info | [53] | |||
| 36 | UCL1972 | Drug Info | [16] | |||
| 37 | VUF 4904 | Drug Info | [88] | |||
| 38 | VUF 5681 | Drug Info | [16] | |||
| 39 | VUF5391 | Drug Info | [16] | |||
| 40 | [123I]iodoproxyfan | Drug Info | [83] | |||
| 41 | [125I]iodophenpropit | Drug Info | [90] | |||
| Modulator | [+] 3 Modulator drugs | + | ||||
| 1 | ABT-288 | Drug Info | [35] | |||
| 2 | ABT-652 | Drug Info | [36] | |||
| 3 | BP-2.94 | Drug Info | [49] | |||
| Inhibitor | [+] 102 Inhibitor drugs | + | ||||
| 1 | Benzo[d]oxazol-2(3H)-one derivative 1 | Drug Info | [23] | |||
| 2 | Benzo[d]oxazol-2(3H)-one derivative 2 | Drug Info | [23] | |||
| 3 | Benzo[d]oxazol-2(3H)-one derivative 3 | Drug Info | [23] | |||
| 4 | Phenylsulfonyl derivative 2 | Drug Info | [23] | |||
| 5 | Phenylsulfonyl derivative 3 | Drug Info | [23] | |||
| 6 | PMID29334795-Compound-62 | Drug Info | [23] | |||
| 7 | PMID29334795-Compound-66 | Drug Info | [23] | |||
| 8 | PMID29334795-Compound-67 | Drug Info | [23] | |||
| 9 | GR-175737 | Drug Info | [52] | |||
| 10 | GT-2016 | Drug Info | [52] | |||
| 11 | (1H-indol-2-yl)(piperazin-1-yl)methanone | Drug Info | [55] | |||
| 12 | (1R,2R)-2-(1H-Imidazol-4-yl)-1-methyl-propylamine | Drug Info | [56] | |||
| 13 | (1R,2S)-2-(1H-Imidazol-4-yl)-1-methyl-propylamine | Drug Info | [56] | |||
| 14 | (1S,2S)-2-(1H-Imidazol-4-yl)-cyclopentylamine | Drug Info | [56] | |||
| 15 | (R)-1-(2-methoxyphenethyl)-2-methylpyrrolidine | Drug Info | [57] | |||
| 16 | (R)-1-(3-methoxyphenethyl)-2-methylpyrrolidine | Drug Info | [57] | |||
| 17 | (R)-1-(4-methoxyphenethyl)-2-methylpyrrolidine | Drug Info | [57] | |||
| 18 | (R)-1-(4-nitrophenethyl)-2-methylpyrrolidine | Drug Info | [57] | |||
| 19 | (R)-2-(2-(2-methylpyrrolidin-1-yl)ethyl)phenol | Drug Info | [57] | |||
| 20 | (R)-2-(2-(2-methylpyrrolidin-1-yl)ethyl)pyridine | Drug Info | [57] | |||
| 21 | (R)-2-methyl-1-(2-m-tolyl-ethyl)-pyrrolidine | Drug Info | [57] | |||
| 22 | (R)-2-methyl-1-(2-p-tolyl-ethyl)-pyrrolidine | Drug Info | [57] | |||
| 23 | (R)-3-(1H-imidazol-4-yl)propyl sec-butylcarbamate | Drug Info | [58] | |||
| 24 | (R)-3-(2-(2-methylpyrrolidin-1-yl)ethyl)pyridine | Drug Info | [57] | |||
| 25 | (R)-6-(2-(2-methylpyrrolidin-1-yl)ethyl)quinoline | Drug Info | [59] | |||
| 26 | (S)-1-(2-methoxyphenethyl)-2-methylpyrrolidine | Drug Info | [57] | |||
| 27 | (S)-1-(3-methoxyphenethyl)-2-methylpyrrolidine | Drug Info | [57] | |||
| 28 | (S)-1-(4-methoxyphenethyl)-2-methylpyrrolidine | Drug Info | [57] | |||
| 29 | (S)-1-(4-nitrophenethyl)-2-methylpyrrolidine | Drug Info | [57] | |||
| 30 | (S)-2-(2-(2-methylpyrrolidin-1-yl)ethyl)phenol | Drug Info | [57] | |||
| 31 | (S)-2-(2-(2-methylpyrrolidin-1-yl)ethyl)pyridine | Drug Info | [57] | |||
| 32 | (S)-2-methyl-1-(2-p-tolyl-ethyl)-pyrrolidine | Drug Info | [57] | |||
| 33 | (S)-3-(1H-imidazol-4-yl)propyl sec-butylcarbamate | Drug Info | [58] | |||
| 34 | (S)-4-(2-(2-methylpyrrolidin-1-yl)ethyl)pyridine | Drug Info | [57] | |||
| 35 | 1-(2-(naphthalen-2-yl)ethyl)pyrrolidine | Drug Info | [57] | |||
| 36 | 1-(2-m-tolyl-ethyl)-pyrrolidine | Drug Info | [57] | |||
| 37 | 1-(2-p-tolyl-ethyl)-pyrrolidine | Drug Info | [57] | |||
| 38 | 1-(3-(2-(3-methoxyphenoxy)ethoxy)propyl)azepane | Drug Info | [63] | |||
| 39 | 1-(3-(3-phenylpropoxy)propyl)piperidine | Drug Info | [64] | |||
| 40 | 1-(3-(4-(2-fluoroethyl)phenoxy)propyl)piperidine | Drug Info | [65] | |||
| 41 | 1-(3-methoxyphenethyl)pyrrolidine | Drug Info | [57] | |||
| 42 | 1-(4-(benzyloxy)phenethyl)pyrrolidine | Drug Info | [57] | |||
| 43 | 1-(4-nitrophenethyl)pyrrolidine | Drug Info | [57] | |||
| 44 | 1-[2-(2,4,6-trimethyl-phenyl)-ethyl]-pyrrolidine | Drug Info | [57] | |||
| 45 | 2-((2-ethoxyphenoxy)methyl)-4-isopropylmorpholine | Drug Info | [66] | |||
| 46 | 2-(1,4'-bipiperidin-1'-yl)thiazolo[4,5-b]pyridine | Drug Info | [67] | |||
| 47 | 2-(1,4'-bipiperidin-1'-yl)thiazolo[4,5-c]pyridine | Drug Info | [67] | |||
| 48 | 2-(2-(4-tert-Butylphenylthio)ethyl)-1H-imidazole | Drug Info | [68] | |||
| 49 | 2-(2-(pyrrolidin-1-yl)ethyl)-1H-indole | Drug Info | [57] | |||
| 50 | 2-(2-(pyrrolidin-1-yl)ethyl)phenol | Drug Info | [57] | |||
| 51 | 2-(2-(pyrrolidin-1-yl)ethyl)pyridine | Drug Info | [57] | |||
| 52 | 2-(3-Methyl-3H-imidazol-4-yl)-ethylamine | Drug Info | [52] | |||
| 53 | 2-(4-Cyclopentyl-piperazin-1-yl)-quinoline | Drug Info | [69] | |||
| 54 | 2-(4-Cyclopropyl-piperazin-1-yl)-quinoline | Drug Info | [69] | |||
| 55 | 2-(4-Isopropyl-piperazin-1-yl)-quinoline | Drug Info | [69] | |||
| 56 | 2-(4-Methyl-piperazin-1-yl)-quinoline | Drug Info | [69] | |||
| 57 | 2-(4-Propyl-piperazin-1-yl)-quinoline | Drug Info | [69] | |||
| 58 | 2-(ethoxycarbonyl)-1H-indole-5-carboxylic acid | Drug Info | [70] | |||
| 59 | 2-[2-(1H-Imidazol-4-yl)-cyclopropyl]-ethylamine | Drug Info | [71] | |||
| 60 | 2-[4-(1-Ethyl-propyl)-piperazin-1-yl]-quinoline | Drug Info | [69] | |||
| 61 | 3-((1H-imidazol-4-yl)methyl)pyridine | Drug Info | [68] | |||
| 62 | 4-((1H-Imidazol-4-yl)methyl)-1-phenylpiperidine | Drug Info | [72] | |||
| 63 | 4-((2R,3S)-2-Methyl-pyrrolidin-3-yl)-1H-imidazole | Drug Info | [56] | |||
| 64 | 4-((2S,3R)-2-Methyl-pyrrolidin-3-yl)-1H-imidazole | Drug Info | [56] | |||
| 65 | 4-(2-(3,4-Dimethylphenylamino)ethyl)-1H-imidazole | Drug Info | [73] | |||
| 66 | 4-(2-(3-tert-Butylphenylamino)ethyl)-1H-imidazole | Drug Info | [73] | |||
| 67 | 4-(2-(4-Methoxyphenylamino)ethyl)-1H-imidazole | Drug Info | [73] | |||
| 68 | 4-(2-(4-Methylphenylamino)ethyl)-1H-imidazole | Drug Info | [73] | |||
| 69 | 4-(2-(Cyclohexylamino)ethyl)-1H-imidazole | Drug Info | [73] | |||
| 70 | 4-(2-(Phenylamino)ethyl)-1H-imidazole | Drug Info | [73] | |||
| 71 | 4-(2-(pyrrolidin-1-yl)ethyl)pyridine | Drug Info | [57] | |||
| 72 | 4-(3-Phenoxy-propyl)-1H-imidazole | Drug Info | [74] | |||
| 73 | 4-(4-butylpiperidin-1-yl)-1-o-tolylbutan-1-one | Drug Info | [75] | |||
| 74 | 4-(6-Cyclohexyl-hex-3-ynyl)-1H-imidazole | Drug Info | [52] | |||
| 75 | 4-(7,7-Dimethyl-oct-3-ynyl)-1H-imidazole | Drug Info | [52] | |||
| 76 | 4-(7-Methyl-oct-3-ynyl)-1H-imidazole | Drug Info | [52] | |||
| 77 | 4-(8-Phenyl-oct-3-ynyl)-1H-imidazole | Drug Info | [52] | |||
| 78 | 4-Benzyl-1-[3-phenylpropoxy)propyl]piperidine | Drug Info | [64] | |||
| 79 | 4-Hex-3-ynyl-1H-imidazole | Drug Info | [52] | |||
| 80 | 4-isopropyl-2-(phenoxymethyl)morpholine | Drug Info | [66] | |||
| 81 | 4-Propyl-1-[3-(phenylpropoxy)propyl]piperidine | Drug Info | [64] | |||
| 82 | 4-[3-(4-Butyl-phenoxy)-propyl]-1H-imidazole | Drug Info | [76] | |||
| 83 | 4-[3-(4-Ethynyl-phenoxy)-propyl]-1H-imidazole | Drug Info | [76] | |||
| 84 | 4-[3-(4-Methoxy-phenoxy)-propyl]-1H-imidazole | Drug Info | [74] | |||
| 85 | 5-(2-(pyrrolidin-1-yl)ethyl)isothiazole | Drug Info | [57] | |||
| 86 | 5-ethyl-2-(2-(pyrrolidin-1-yl)ethyl)pyridine | Drug Info | [57] | |||
| 87 | 5-methoxy-2-(2-(pyrrolidin-1-yl)ethyl)-1H-indole | Drug Info | [57] | |||
| 88 | 5-phenyl-2-(4-(piperidin-1-yl)butyl)oxazole | Drug Info | [77] | |||
| 89 | Aerophobin-1 | Drug Info | [79] | |||
| 90 | APLYSAMINE | Drug Info | [80] | |||
| 91 | C-[2-(1H-Imidazol-4-yl)-cyclopropyl]-methylamine | Drug Info | [71] | |||
| 92 | CARCININE | Drug Info | [80] | |||
| 93 | CONESSINE | Drug Info | [81] | |||
| 94 | Des-bromoaplysamine-1 | Drug Info | [82] | |||
| 95 | IODOPROXYFAN | Drug Info | [74] | |||
| 96 | JNJ-28583867 | Drug Info | [85] | |||
| 97 | N-benzyl-4-cyclopentylpiperazine-1-carboxamide | Drug Info | [86] | |||
| 98 | ST-1025 | Drug Info | [77] | |||
| 99 | ST-1093 | Drug Info | [77] | |||
| 100 | UCL-2138 | Drug Info | [65] | |||
| 101 | VUF-10214 | Drug Info | [89] | |||
| 102 | VUF-5297 | Drug Info | [71] | |||
| Ligand | [+] 9 Ligand drugs | + | ||||
| 1 | Piperazine carbamate/urea derivative 1 | Drug Info | [23] | |||
| 2 | Piperazine carbamate/urea derivative 2 | Drug Info | [23] | |||
| 3 | Piperazine carbamate/urea derivative 3 | Drug Info | [23] | |||
| 4 | Piperazine carbamate/urea derivative 4 | Drug Info | [23] | |||
| 5 | Piperazine carbamate/urea derivative 5 | Drug Info | [23] | |||
| 6 | Piperazine carbamate/urea derivative 6 | Drug Info | [23] | |||
| 7 | Piperazine carbamate/urea derivative 7 | Drug Info | [23] | |||
| 8 | Triazolo-benzodiazepine derivative 1 | Drug Info | [23] | |||
| 9 | Triazolo-benzodiazepine derivative 2 | Drug Info | [23] | |||
| Agonis; Inverse agonist | [+] 1 Agonis; Inverse agonist drugs | + | ||||
| 1 | PMID29334795-Compound-22 | Drug Info | [23] | |||
| Inverse agonist | [+] 4 Inverse agonist drugs | + | ||||
| 1 | PMID29334795-Compound-23 | Drug Info | [23] | |||
| 2 | PMID29334795-Compound-24 | Drug Info | [23] | |||
| 3 | PMID29334795-Compound-25 | Drug Info | [23] | |||
| 4 | Pyridazin-3(2H)-one derivative 1 | Drug Info | [23] | |||
| Binder | [+] 1 Binder drugs | + | ||||
| 1 | Cipralisant | Drug Info | [50] | |||
| Cell-based Target Expression Variations | Top | |||||
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| Cell-based Target Expression Variations | ||||||
| Drug Binding Sites of Target | Top | |||||
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| Ligand Name: Cholesterol | Ligand Info | |||||
| Structure Description | Crystal structure of human histamine receptor H3R in complex with antagonist PF03654746 | PDB:7F61 | ||||
| Method | X-ray diffraction | Resolution | 2.60 Å | Mutation | Yes | [91] |
| PDB Sequence |
RGFSAAWTAV
36 LAALMALLIV46 ATVLGNALVM56 LAFVADSSLR66 TQNNFFLLNL76 AISDFLVGAF 86 CIPLYVPYVL96 TGRWTFGRGL106 CKLWLVVDYL116 LCTSKAFNIV126 LISYDRFLSV 136 TRAVSYRAQQ146 GDTRRAVRKM156 LLVWVLAFLL166 YGPAILSWEY176 LSGGSSIPEG 186 HCYAEFFYNW196 YFLITASTLE206 FFTPFLSVTF216 FNLSIYLNIQ226 RRTRLRLDGA 236 REAAGRFRLS351 RDRKVAKSLA361 VIVSIFGLCW371 APYTLLMIIR381 AACHGHCVPD 391 YWYETSFWLL401 WANSAVNPVL411 YPLCHHSFRR421 AFTKLLCPQK431 L |
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| Ligand Name: N-ethyl-3-fluoro-3-[3-fluoro-4-(pyrrolidin-1-ylmethyl)phenyl]cyclobutane-1-carboxamide | Ligand Info | |||||
| Structure Description | Crystal structure of human histamine receptor H3R in complex with antagonist PF03654746 | PDB:7F61 | ||||
| Method | X-ray diffraction | Resolution | 2.60 Å | Mutation | Yes | [91] |
| PDB Sequence |
RGFSAAWTAV
36 LAALMALLIV46 ATVLGNALVM56 LAFVADSSLR66 TQNNFFLLNL76 AISDFLVGAF 86 CIPLYVPYVL96 TGRWTFGRGL106 CKLWLVVDYL116 LCTSKAFNIV126 LISYDRFLSV 136 TRAVSYRAQQ146 GDTRRAVRKM156 LLVWVLAFLL166 YGPAILSWEY176 LSGGSSIPEG 186 HCYAEFFYNW196 YFLITASTLE206 FFTPFLSVTF216 FNLSIYLNIQ226 RRTRLRLDGA 236 REAAGRFRLS351 RDRKVAKSLA361 VIVSIFGLCW371 APYTLLMIIR381 AACHGHCVPD 391 YWYETSFWLL401 WANSAVNPVL411 YPLCHHSFRR421 AFTKLLCPQK431 L |
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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 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).
Human Similarity Proteins
Human Pathway Affiliation
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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 | ||
| 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 | ||
| 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 | [+] 1 KEGG Pathways | + | ||||
| 1 | Neuroactive ligand-receptor interaction | |||||
| Reactome | [+] 2 Reactome Pathways | + | ||||
| 1 | Histamine receptors | |||||
| 2 | G alpha (i) signalling events | |||||
| WikiPathways | [+] 4 WikiPathways | + | ||||
| 1 | Monoamine Transport | |||||
| 2 | GPCRs, Class A Rhodopsin-like | |||||
| 3 | GPCR ligand binding | |||||
| 4 | GPCR downstream signaling | |||||
| Target-Related Models and Studies | Top | |||||
|---|---|---|---|---|---|---|
| Target Validation | ||||||
| Target QSAR Model | ||||||
| References | Top | |||||
|---|---|---|---|---|---|---|
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| REF 3 | Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA) | |||||
| REF 4 | Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA) | |||||
| REF 5 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800032202) | |||||
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| REF 28 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800028155) | |||||
| REF 29 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800033674) | |||||
| REF 30 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800001957) | |||||
| REF 31 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800008938) | |||||
| REF 32 | 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: 1267). | |||||
| REF 33 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800004362) | |||||
| REF 34 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800005172) | |||||
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