| Target Validation Information | |||||
|---|---|---|---|---|---|
| Target ID | T51666 | ||||
| Target Name | Potassium-transporting ATPase alpha chain 1 | ||||
| Target Type | Successful |
||||
| Drug Potency against Target | Rabeprazole | Drug Info | Ki = 1600 nM | [552838] | |
| Lansoprazole | Drug Info | Ki = 0.4~1.5 uM | [552597] | ||
| Pantoprazole | Drug Info | IC50 = 6800 nM | [552372] | ||
| Action against Disease Model | Omeprazole | 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. | [553150] | Drug Info | |
| Lansoprazole | IC50 on acid formation stimulated by dibutyryl cyclic AMP in isolated canine parietal cells: 59/82nM | [552592] | Drug Info | ||
| References | |||||
| Ref 553150 | Omeprazole, cimetidine, and ranitidine: inhibition of acid production in isolated human parietal cells. Scand J Gastroenterol. 1985 Oct;20(8):917-21. | ||||
| Ref 552592 | Effects of the enantiomers of lansoprazole (AG-1749) on (H+ + K+)-ATPase activity in canine gastric microsomes and acid formation in isolated canine parietal cells. Biochem Pharmacol. 1991 Oct 24;42(10):1875-8. | ||||
| Ref 552838 | Drug target identification using side-effect similarity. Science. 2008 Jul 11;321(5886):263-6. doi: 10.1126/science.1158140. | ||||
| Ref 552597 | Development and validation of an in silico P450 profiler based on pharmacophore models. Curr Drug Discov Technol. 2006 Mar;3(1):1-48. | ||||
| Ref 552372 | Pantoprazole: a novel H+/K(+)-ATPase inhibitor with an improved pH stability. Eur J Pharmacol. 1992 Aug 6;218(2-3):265-71. | ||||
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