Target Validation Information | |||||
---|---|---|---|---|---|
TTD ID | T64765 | ||||
Target Name | Histamine H3 receptor (H3R) | ||||
Type of Target |
Successful |
||||
Drug Potency against Target | ABT-239 | Drug Info | Ki = 0.45 nM | [31] | |
Cipralisant | Drug Info | Ki = 5.25 nM | [30] | ||
Drug Info | Ki = 42.2 nM | [3] | |||
(1H-indol-2-yl)(piperazin-1-yl)methanone | Drug Info | Ki = 9000 nM | [7] | ||
(1R,2R)-2-(1H-Imidazol-4-yl)-1-methyl-propylamine | Drug Info | Ki = 11 nM | [27] | ||
(1R,2S)-2-(1H-Imidazol-4-yl)-1-methyl-propylamine | Drug Info | Ki = 0.8 nM | [27] | ||
(1S,2S)-2-(1H-Imidazol-4-yl)-cyclopentylamine | Drug Info | Ki = 740 nM | [27] | ||
(R)-1-(2-methoxyphenethyl)-2-methylpyrrolidine | Drug Info | Ki = 110 nM | [10] | ||
(R)-1-(3-methoxyphenethyl)-2-methylpyrrolidine | Drug Info | Ki = 160 nM | [10] | ||
(R)-1-(4-methoxyphenethyl)-2-methylpyrrolidine | Drug Info | Ki = 12 nM | [10] | ||
(R)-1-(4-nitrophenethyl)-2-methylpyrrolidine | Drug Info | Ki = 280 nM | [10] | ||
(R)-2-(2-(2-methylpyrrolidin-1-yl)ethyl)phenol | Drug Info | Ki = 240 nM | [10] | ||
(R)-2-(2-(2-methylpyrrolidin-1-yl)ethyl)pyridine | Drug Info | Ki = 200 nM | [10] | ||
(R)-2-methyl-1-(2-m-tolyl-ethyl)-pyrrolidine | Drug Info | Ki = 30 nM | [10] | ||
(R)-2-methyl-1-(2-p-tolyl-ethyl)-pyrrolidine | Drug Info | Ki = 37 nM | [10] | ||
(R)-3-(1H-imidazol-4-yl)propyl sec-butylcarbamate | Drug Info | Ki = 19 nM | [20] | ||
(R)-3-(2-(2-methylpyrrolidin-1-yl)ethyl)pyridine | Drug Info | Ki = 320 nM | [10] | ||
(R)-4-(2-(2-methylpyrrolidin-1-yl)ethyl)pyridine | Drug Info | Ki = 320 nM | [10] | ||
(R)-6-(2-(2-methylpyrrolidin-1-yl)ethyl)quinoline | Drug Info | Ki = 41 nM | [22] | ||
(S)-1-(2-methoxyphenethyl)-2-methylpyrrolidine | Drug Info | Ki = 240 nM | [10] | ||
(S)-1-(3-methoxyphenethyl)-2-methylpyrrolidine | Drug Info | Ki = 170 nM | [10] | ||
(S)-1-(4-methoxyphenethyl)-2-methylpyrrolidine | Drug Info | Ki = 63 nM | [10] | ||
(S)-1-(4-nitrophenethyl)-2-methylpyrrolidine | Drug Info | Ki = 260 nM | [10] | ||
(S)-2-(2-(2-methylpyrrolidin-1-yl)ethyl)phenol | Drug Info | Ki = 220 nM | [10] | ||
(S)-2-(2-(2-methylpyrrolidin-1-yl)ethyl)pyridine | Drug Info | Ki = 340 nM | [10] | ||
(S)-2-methyl-1-(2-m-tolyl-ethyl)-pyrrolidine | Drug Info | Ki = 240 nM | [10] | ||
(S)-2-methyl-1-(2-p-tolyl-ethyl)-pyrrolidine | Drug Info | Ki = 330 nM | [10] | ||
(S)-3-(1H-imidazol-4-yl)propyl sec-butylcarbamate | Drug Info | Ki = 23 nM | [20] | ||
(S)-4-(2-(2-methylpyrrolidin-1-yl)ethyl)pyridine | Drug Info | Ki = 140 nM | [10] | ||
1-(2-(naphthalen-2-yl)ethyl)pyrrolidine | Drug Info | Ki = 30 nM | [10] | ||
1-(2-m-tolyl-ethyl)-pyrrolidine | Drug Info | Ki = 200 nM | [10] | ||
1-(2-methoxyphenethyl)pyrrolidine | Drug Info | Ki = 260 nM | [10] | ||
1-(2-p-tolyl-ethyl)-pyrrolidine | Drug Info | Ki = 81 nM | [10] | ||
1-(3-(2-(3-methoxyphenoxy)ethoxy)propyl)azepane | Drug Info | Ki = 62 nM | [16] | ||
1-(3-(3-phenylpropoxy)propyl)piperidine | Drug Info | Ki = 3.1 nM | [13] | ||
1-(3-(4-(2-fluoroethyl)phenoxy)propyl)piperidine | Drug Info | Ki = 43 nM | [15] | ||
1-(3-(4-(fluoromethyl)phenoxy)propyl)piperidine | Drug Info | Ki = 17.3 nM | [15] | ||
1-(3-methoxyphenethyl)pyrrolidine | Drug Info | Ki = 260 nM | [10] | ||
1-(4-(benzyloxy)phenethyl)pyrrolidine | Drug Info | Ki = 40 nM | [10] | ||
1-(4-methoxyphenethyl)pyrrolidine | Drug Info | Ki = 370 nM | [10] | ||
1-(4-nitrophenethyl)pyrrolidine | Drug Info | Ki = 360 nM | [10] | ||
1-[2-(2,4,6-trimethyl-phenyl)-ethyl]-pyrrolidine | Drug Info | Ki = 230 nM | [10] | ||
2-((1H-imidazol-4-yl)methyl)pyridine | Drug Info | Ki = 1800 nM | [24] | ||
2-((2-ethoxyphenoxy)methyl)-4-isopropylmorpholine | Drug Info | Ki = 9000 nM | [14] | ||
2-(1,4'-bipiperidin-1'-yl)thiazolo[4,5-b]pyridine | Drug Info | Ki = 139 nM | [19] | ||
2-(1,4'-bipiperidin-1'-yl)thiazolo[4,5-c]pyridine | Drug Info | Ki = 128 nM | [19] | ||
2-(2-(4-tert-Butylphenylthio)ethyl)-1H-imidazole | Drug Info | Ki = 0.43 nM | [24] | ||
2-(2-(pyrrolidin-1-yl)ethyl)-1H-indole | Drug Info | Ki = 219 nM | [10] | ||
2-(2-(pyrrolidin-1-yl)ethyl)phenol | Drug Info | Ki = 340 nM | [10] | ||
2-(2-(pyrrolidin-1-yl)ethyl)pyridine | Drug Info | Ki = 320 nM | [10] | ||
2-(3-Methyl-3H-imidazol-4-yl)-ethylamine | Drug Info | Ki = 1 nM | [28] | ||
2-(4-Cyclopentyl-piperazin-1-yl)-quinoline | Drug Info | Ki = 28 nM | [4] | ||
2-(4-Cyclopropyl-piperazin-1-yl)-quinoline | Drug Info | Ki = 13 nM | [4] | ||
2-(4-Isopropyl-piperazin-1-yl)-quinoline | Drug Info | Ki = 6.8 nM | [4] | ||
2-(4-Methyl-piperazin-1-yl)-quinoline | Drug Info | Ki = 410 nM | [4] | ||
2-(4-Propyl-piperazin-1-yl)-quinoline | Drug Info | Ki = 6 nM | [4] | ||
2-(ethoxycarbonyl)-1H-indole-5-carboxylic acid | Drug Info | Ki = 7 nM | [17] | ||
2-[4-(1-Ethyl-propyl)-piperazin-1-yl]-quinoline | Drug Info | Ki = 2.9 nM | [4] | ||
3-((1H-imidazol-4-yl)methyl)pyridine | Drug Info | Ki = 76 nM | [24] | ||
4-((1H-imidazol-4-yl)methyl)-1-heptylpiperidine | Drug Info | Ki = 2 nM | [5] | ||
4-((1H-Imidazol-4-yl)methyl)-1-phenylpiperidine | Drug Info | Ki = 30 nM | |||
4-((2R,3S)-2-Methyl-pyrrolidin-3-yl)-1H-imidazole | Drug Info | Ki = 8.7 nM | [27] | ||
4-((2S,3R)-2-Methyl-pyrrolidin-3-yl)-1H-imidazole | Drug Info | Ki = 33 nM | [27] | ||
4-(2-(3,4-Dimethylphenylamino)ethyl)-1H-imidazole | Drug Info | Ki = 9.9 nM | [21] | ||
4-(2-(3-tert-Butylphenylamino)ethyl)-1H-imidazole | Drug Info | Ki = 2.2 nM | [21] | ||
4-(2-(4-Cyclohexylphenylamino)ethyl)-1H-imidazole | Drug Info | Ki = 4.1 nM | [21] | ||
4-(2-(4-Methoxyphenylamino)ethyl)-1H-imidazole | Drug Info | Ki = 24 nM | [21] | ||
4-(2-(4-Methylphenylamino)ethyl)-1H-imidazole | Drug Info | Ki = 14 nM | [21] | ||
4-(2-(4-tert-Butylphenylamino)ethyl)-1H-imidazole | Drug Info | Ki = 0.89 nM | [21] | ||
4-(2-(Cyclohexylamino)ethyl)-1H-imidazole | Drug Info | Ki = 1600 nM | [21] | ||
4-(2-(Phenylamino)ethyl)-1H-imidazole | Drug Info | Ki = 56 nM | [21] | ||
4-(2-(pyrrolidin-1-yl)ethyl)pyridine | Drug Info | Ki = 320 nM | [10] | ||
4-(3-Phenoxy-propyl)-1H-imidazole | Drug Info | Ki = 4.9 nM | [2] | ||
4-(4-butylpiperidin-1-yl)-1-o-tolylbutan-1-one | Drug Info | Ki < 1000 nM | [23] | ||
4-(6-Cyclohexyl-hex-3-ynyl)-1H-imidazole | Drug Info | Ki = 2.9 nM | [28] | ||
4-(6-Cyclopentyl-hex-3-ynyl)-1H-imidazole | Drug Info | Ki = 0.95 nM | [28] | ||
4-(7,7-Dimethyl-oct-3-ynyl)-1H-imidazole | Drug Info | Ki = 0.8 nM | [28] | ||
4-(7-Methyl-oct-3-ynyl)-1H-imidazole | Drug Info | Ki = 3.7 nM | [28] | ||
4-(8-Phenyl-oct-3-ynyl)-1H-imidazole | Drug Info | Ki = 3.5 nM | [28] | ||
4-Benzyl-1-[3-phenylpropoxy)propyl]piperidine | Drug Info | Ki = 326 nM | [13] | ||
4-Butyl-1-[3-(phenylpropoxy)propyl]piperidine | Drug Info | Ki = 274 nM | [13] | ||
4-Hept-3-ynyl-1H-imidazole | Drug Info | Ki = 27 nM | [28] | ||
4-Hex-3-ynyl-1H-imidazole | Drug Info | Ki = 79 nM | [28] | ||
4-isopropyl-2-(phenoxymethyl)morpholine | Drug Info | Ki = 4800 nM | [14] | ||
4-Propyl-1-[3-(phenylpropoxy)propyl]piperidine | Drug Info | Ki = 249 nM | [13] | ||
4-[3-(4-Butyl-phenoxy)-propyl]-1H-imidazole | Drug Info | Ki = 60 nM | [1] | ||
4-[3-(4-Ethynyl-phenoxy)-propyl]-1H-imidazole | Drug Info | Ki = 2.3 nM | [1] | ||
4-[3-(4-Methoxy-phenoxy)-propyl]-1H-imidazole | Drug Info | Ki = 7.9 nM | [2] | ||
5-(2-(pyrrolidin-1-yl)ethyl)isothiazole | Drug Info | Ki = 190 nM | [10] | ||
5-ethyl-2-(2-(pyrrolidin-1-yl)ethyl)pyridine | Drug Info | Ki = 160 nM | [10] | ||
5-methoxy-2-(2-(pyrrolidin-1-yl)ethyl)-1H-indole | Drug Info | Ki = 230 nM | [10] | ||
5-phenyl-2-(4-(piperidin-1-yl)butyl)oxazole | Drug Info | Ki = 63 nM | [25] | ||
A-317920 | Drug Info | Ki = 12 nM | [11] | ||
Aerophobin-1 | Drug Info | IC50 = 9000 nM | |||
APLYSAMINE | Drug Info | IC50 = 500 nM | [12] | ||
CARCININE | Drug Info | Ki = 294 nM | [12] | ||
CONESSINE | Drug Info | Ki = 24.5 nM | [18] | ||
Des-bromoaplysamine-1 | Drug Info | Ki = 89 nM | [6] | ||
FUB 349 | Drug Info | Ki = 12 nM | [2] | ||
GR-175737 | Drug Info | Ki = 7 nM | [28] | ||
GSK189254A | Drug Info | Ki = 0.26 nM | [26] | ||
GT-2016 | Drug Info | Ki = 40 nM | [28] | ||
IODOPROXYFAN | Drug Info | Ki = 71 nM | [2] | ||
JNJ-28583867 | Drug Info | Ki = 10.6 nM | [9] | ||
N-benzyl-4-cyclopentylpiperazine-1-carboxamide | Drug Info | Ki = 94 nM | [8] | ||
N-methyl-2-(pyridin-2-yl)ethanamine | Drug Info | Ki = 2030 nM | [17] | ||
Pitolisant | Drug Info | Ki = 0.16 nM | [16] | ||
ST-1025 | Drug Info | Ki = 11.2 nM | [25] | ||
ST-1093 | Drug Info | Ki = 20 nM | [25] | ||
UCL-2138 | Drug Info | Ki = 11 nM | [15] | ||
Verongamine | Drug Info | IC50 = 500 nM | |||
VUF-5297 | Drug Info | Ki = 4.3 nM | [3] | ||
Action against Disease Model | Cipralisant | Drug Info | GT-2331 demonstrated full agonism relative to (R)-alpha-methylhistamine in cAMP assays. In [35S]GTPgammaS binding assays, GT-2331 demonstrated partial agonism. Imetit showed full agonism in most assays, but it was slightly less efficacious in a neurotransmitter release assay and in [35S]GTPgammaS binding at the h uMan H3 receptor. To further examine these ligands, we coexpressed G alpha16 or chimeric G alpha q/i5 in h uMan embryonic kidney cells expressing the h uMan H3 receptor and assayed intracellular calci uM and cAMP levels. GT-2331 demonstrated full agonism in all assays of cAMP activity. However, in cells expressing G alpha16, they exhibited minimal agonism in calci uM mobilization assays, whereas imetit showed partial agonism. When G alpha q/i5 was used, the activity of both GT-2331 and proxyfan increased, whereas imetit became a full agonist | [29] | |
References | |||||
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REF 19 | Synthesis and structure-activity relationships of 2-(1,4'-bipiperidin-1'-yl)thiazolopyridine as H3 receptor antagonists. Bioorg Med Chem Lett. 2009 Nov 1;19(21):6176-80. | ||||
REF 20 | Histamine H3 and H4 receptor affinity of branched 3-(1H-imidazol-4-yl)propyl N-alkylcarbamates. Bioorg Med Chem Lett. 2009 Dec 1;19(23):6682-5. | ||||
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REF 22 | In vitro studies on a class of quinoline containing histamine H3 antagonists. Bioorg Med Chem Lett. 2010 Jun 1;20(11):3295-300. | ||||
REF 23 | Discovery of N-{1-[3-(3-oxo-2,3-dihydrobenzo[1,4]oxazin-4-yl)propyl]piperidin-4-yl}-2-phenylacetamide (Lu AE51090): an allosteric muscarinic M1 rec... J Med Chem. 2010 Sep 9;53(17):6386-97. | ||||
REF 24 | Investigation of the histamine H3 receptor binding site. Design and synthesis of hybrid agonists with a lipophilic side chain. J Med Chem. 2010 Sep 9;53(17):6445-56. | ||||
REF 25 | Azole derivatives as histamine H3 receptor antagonists, part 2: C-C and C-S coupled heterocycles. Bioorg Med Chem Lett. 2010 Oct 1;20(19):5883-6. | ||||
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