1-[5-(2-Fluorophenyl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrol-3-yl]-N-methylmethanamine monofumarate (TAK-438), a novel and potent potassium-competitive acid blocker for the treatment of acid-related diseases

The Journal of Pharmacology and Experimental Therapeutics
Yasunobu HoriNobuhiro Inatomi

Abstract

Proton pump inhibitors (PPIs) are widely used in the treatment of acid-related diseases. However, several unmet medical needs, such as suppression of night-time acid secretion and rapid symptom relief, remain. In this study, we investigated the pharmacological effects of 1-[5-(2-fluorophenyl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrol-3-yl]-N-methylmethanamine monofumarate (TAK-438), a novel potassium-competitive acid blocker (P-CAB), on gastric acid secretion in comparison with lansoprazole, a typical PPI, and SCH28080 [3-(cyanomethyl)-2-methyl,8-(phenylmethoxy)imidazo(1,2-a)pyridine], a prototype of P-CAB. TAK-438, SCH28080, and lansoprazole inhibited H(+),K(+)-ATPase activity in porcine gastric microsomes with IC(50) values of 0.019, 0.14, and 7.6 μM, respectively, at pH 6.5. The inhibitory activity of TAK-438 was unaffected by ambient pH, whereas the inhibitory activities of SCH28080 and lansoprazole were weaker at pH 7.5. The inhibition by TAK-438 and SCH28080 was reversible and achieved in a K(+)-competitive manner, quite different from that by lansoprazole. TAK-438, at a dose of 4 mg/kg (as the free base) orally, completely inhibited basal and 2-deoxy-d-glucose-stimulated gastric acid secretion in rats, and its effect on both wa...Continue Reading

References

Jan 1, 1988·Annual Review of Pharmacology and Toxicology·G SachsB Wallmark
Jan 1, 1995·Annual Review of Pharmacology and Toxicology·G SachsS Hersey
Apr 28, 1999·Archives of Internal Medicine·R H Hunt
Nov 24, 1999·European Journal of Gastroenterology & Hepatology·H G Dammann, F Burkhardt
Jun 10, 2000·Alimentary Pharmacology & Therapeutics·P O KatzD O Castell
Jun 30, 2000·Japanese Journal of Pharmacology·Y TsukimiH Tanaka
May 9, 2001·Biochimica Et Biophysica Acta·S A MousaviA Brech
Sep 13, 2003·Alimentary Pharmacology & Therapeutics·P MalfertheinerW Fuchs
Dec 19, 2003·Journal of Clinical Pharmacology·Kyung-Sang YuByoung-Seok Moon
May 11, 2005·Expert Opinion on Investigational Drugs·Michael E Parsons, David J Keeling
Jun 1, 2005·International Journal of Clinical Practice·M Robinson
Jul 1, 2005·Drug Metabolism and Pharmacokinetics·Takahisa FurutaTakashi Ishizaki
Jul 8, 2005·Pharmacology & Therapeutics·Kjell Andersson, Enar Carlsson
Jul 14, 2005·Alimentary Pharmacology & Therapeutics·R FassJ Sewell
Sep 9, 2005·World Journal of Gastroenterology : WJG·John-P Geibel
May 17, 2006·Alimentary Pharmacology & Therapeutics·P O KatzA N Barkun
Nov 4, 2006·Biochemical Pharmacology·Karin GeddaKjell Andersson
Mar 21, 2007·The Journal of Pharmacology and Experimental Therapeutics·W A SimonS Postius
Sep 14, 2007·Scandinavian Journal of Gastroenterology·Michael HerrmannThomas Klein
Oct 24, 2007·Clinical Gastroenterology and Hepatology : the Official Clinical Practice Journal of the American Gastroenterological Association·Peter J KahrilasGoran Hasselgren

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Citations

Oct 7, 2010·Current Gastroenterology Reports·George SachsRichard Hunt
May 24, 2014·Digestive Diseases and Sciences·George SachsDavid R Scott
Feb 21, 2016·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Tomoki YoneyamaSatoru Asahi
Jan 13, 2016·Alimentary Pharmacology & Therapeutics·P O Katz, F Schnoll-Sussman
Jul 16, 2011·Angewandte Chemie·Tao XuGuosheng Liu
Sep 29, 2011·Annals of the New York Academy of Sciences·Joel E RichterRichard H Hunt
Mar 7, 2015·Drugs·Karly P Garnock-Jones
May 27, 2016·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Akifumi KogameSatoru Asahi
Jun 12, 2016·Advances in Therapy·Kazuyoshi OtakeNobuhiro Inatomi
Jul 15, 2016·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Hitomi YamasakiSatoru Asahi
Aug 16, 2016·Pharmacology & Therapeutics·Nobuhiro InatomiKazuyoshi Otake
Aug 6, 2016·Digestive Endoscopy : Official Journal of the Japan Gastroenterological Endoscopy Society·Daisuke MaruokaOsamu Yokosuka
Jul 19, 2016·Expert Opinion on Drug Metabolism & Toxicology·Edoardo SavarinoCorrado Blandizzi
Nov 3, 2016·Therapeutic Advances in Gastroenterology·Yuko AkazawaYutaka Fukuda
Mar 8, 2017·Digestive Endoscopy : Official Journal of the Japan Gastroenterological Endoscopy Society·Izumi TsuchiyaMotoyoshi Izumi
Jun 29, 2017·Expert Opinion on Pharmacotherapy·Irene MartinucciEdoardo Savarino
Jun 21, 2017·European Journal of Pharmacology·Cheng-Yuan LiYun-Man Li
Apr 17, 2018·Journal of Applied Toxicology : JAT·Tianyi LiXuejun He
Nov 22, 2016·World Journal of Gastrointestinal Pharmacology and Therapeutics·Shinya YamadaNorimasa Yoshida
May 10, 2018·Journal of Neurogastroenterology and Motility·Tadayuki Oshima, Hiroto Miwa
Sep 7, 2018·Nihon yakurigaku zasshi. Folia pharmacologica Japonica·Jun MatsukawaYasuhiro Tsukimi
Mar 19, 2019·Journal of Gastroenterology and Hepatology·Hirota MiyazakiToshiro Tango
Jun 28, 2019·Internal Medicine·Shu KiyotokiIsao Sakaida
Nov 29, 2017·The Journal of Pharmacology and Experimental Therapeutics·Nobuyuki Takahashi, Yukinori Take
Mar 22, 2019·The Journal of Pharmacology and Experimental Therapeutics·Dong Kyu KimShin-Young Ryu
Mar 18, 2011·The Journal of Pharmacology and Experimental Therapeutics·Yasunobu HoriNobuhiro Inatomi

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