| Target Validation Information | |||||
|---|---|---|---|---|---|
| TTD ID | T30985 | ||||
| Target Name | Histamine H2 receptor (H2R) | ||||
| Type of Target |
Successful |
||||
| Drug Potency against Target | Cimetidine | Drug Info | IC50 = 370 nM | [5] | |
| Famotidine | Drug Info | Ki = 18 nM | [6] | ||
| Nizatidine | Drug Info | Ki = 7.1 nM | [6] | ||
| Ranitidine | Drug Info | Ki = 135 nM | [6] | ||
| (+/-)-nantenine | Drug Info | Ki = 672 nM | [2] | ||
| 4-(4-butylpiperidin-1-yl)-1-o-tolylbutan-1-one | Drug Info | Ki < 1000 nM | [3] | ||
| WAY-207024 | Drug Info | Ki = 850 nM | [1] | ||
| Action against Disease Model | Cimetidine | Drug Info | IC50 on acid production stimulated via H2-receptors by 5000nM of histamine: 1000nM | [7] | |
| Famotidine | Drug Info | The antisecretory properties of omeprazole, cimetidine, and ranitidine were studied in vitro, using h uMan gastric mucosal cells, which were obtained by sequential pronase and collagenase incubation of small tissue specimens obtained by endoscopic biopsy. Acid production was measured as the acc uMulation of radioactive aminopyrine in the acid compartments of the parietal cells. Acid production was stimulated via H2-receptors by histamine (10(-4) M or 5 X 10(-6) M) and via intracellular mechanisms by db-cAMP (10(-3) M). Omeprazole induced a dose-dependent inhibition of acid production for all stimulators (IC50 = 2 X 10(-7) M and 3 X 10(-8) M with high and low concentrations of histamine, respectively, and 5 X 10(-6) M with db-cAMP). The H2-receptor antagonists dose-dependently inhibited the histamine-stimulated acid production (IC50 for cimetidine = 10(-5) M and 10(-6) M and for ranitidine = 10(-5) M and 2 X 10(-7) M for high and low concentrations of histamine, respectively). Neither cimetidine nor ranitidine inhibited acid production after intracellular stimulation with db-cAMP. Omeprazole reduced the aminopyrine acc uMulation stimulated by histamine (10(-4)M) already within 5-10 min, whereas cimetidine (10(-3) M and ranitidine (10(-4) M) required 20-30 min. The unstimulated level of acid production was also inhibited by omeprazole but not by the H2-receptor antagonists.Histamine-induced adenylate cyclase activation was abolished IC50: 300 nM | [4] | ||
| Ranitidine | Drug Info | The antisecretory properties of omeprazole, cimetidine, and ranitidine were studied in vitro, using h uMan gastric mucosal cells, which were obtained by sequential pronase and collagenase incubation of small tissue specimens obtained by endoscopic biopsy. Acid production was measured as the acc uMulation of radioactive aminopyrine in the acid compartments of the parietal cells. Acid production was stimulated via H2-receptors by histamine (10(-4) M or 5 X 10(-6) M) and via intracellular mechanisms by db-cAMP (10(-3) M). Omeprazole induced a dose-dependent inhibition of acid production for all stimulators (IC50 = 2 X 10(-7) M and 3 X 10(-8) M with high and low concentrations of histamine, respectively, and 5 X 10(-6) M with db-cAMP). The H2-receptor antagonists dose-dependently inhibited the histamine-stimulated acid production (IC50 for cimetidine = 10(-5) M and 10(-6) M and for ranitidine = 10(-5) M and 2 X 10(-7) M for high and low concentrations of histamine, respectively). Neither cimetidine nor ranitidine inhibited acid production after intracellular stimulation with db-cAMP. Omeprazole reduced the aminopyrine acc uMulation stimulated by histamine (10(-4)M) already within 5-10 min, whereas cimetidine (10(-3) M and ranitidine (10(-4) M) required 20-30 min. The unstimulated level of acid production was also inhibited by omeprazole but not by the H2-receptor antagonists.IC50 on acid production stimulated via H2-receptors by 5000nM of histamine: 200nM | [7] | ||
| References | |||||
| REF 1 | Discovery of 6-({4-[2-(4-tert-butylphenyl)-1H-benzimidazol-4-yl]piperazin-1-yl}methyl)quinoxaline (WAY-207024): an orally active antagonist of the ... J Med Chem. 2009 Apr 9;52(7):2148-52. | ||||
| REF 2 | Synthetic studies and pharmacological evaluations on the MDMA ('Ecstasy') antagonist nantenine. Bioorg Med Chem Lett. 2010 Jan 15;20(2):628-31. | ||||
| REF 3 | 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 4 | Pharmacological control of the human gastric histamine H2 receptor by famotidine: comparison with H1, H2 and H3 receptor agonists and antagonists. Eur J Clin Invest. 1989 Feb;19(1):1-10. | ||||
| REF 5 | Enhancement by histamine of vascular endothelial growth factor production in granulation tissue via H(2) receptors. Br J Pharmacol. 2001 Dec;134(7):1419-28. | ||||
| REF 6 | Second-generation histamine H(2)-receptor antagonists with gastric mucosal defensive properties. Mini Rev Med Chem. 2009 May;9(5):581-9. | ||||
| REF 7 | Omeprazole, cimetidine, and ranitidine: inhibition of acid production in isolated human parietal cells. Scand J Gastroenterol. 1985 Oct;20(8):917-21. | ||||
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