TAK-438

"目录号: HY-15295

Membrane Transporter/Ion Channel-

TAK-438是钾竞争性的酸阻滞剂,能可逆的抑制H_addition_/K_addition_-ATPase,IC50为19 nM(pH 6.5)。

Proton Pump

相关产品

Omeprazole-Pantoprazole sodium-(R)-Lansoprazole-Zinc Pyrithione-AZD0865-Ilaprazole-Esomeprazole Magnesium trihydrate-TAK-438 free base-Bamaquimast-Rabeprazole sodium-Soraprazan-Chebulinic acid-Picoprazole-SKF96067-Tenatoprazole sodium-

生物活性

Description

TAK-438 is a novel P-CAB (potassium-competitive acid blocker) that reversibly inhibits H+/K+, ATPase with IC50 of 19 nM (pH 6.5), controls gastric acid secretion.IC50 value: 19 nM [1]Target: H+/K+ATPasein vitro: TAK-438 is a pyrrole derivative with a chemical structure that is completely different from the P-CABs developed to date. TAK-438 inhibits gastric H+, K+-ATPase activity in a concentration-dependent manner. Under neutral conditions (pH 7.5), the inhibitory activity of TAK-438 is almost the same as that under weakly acidic conditions (pH 6.5). TAK-438 does not inhibit Na+, K+-ATPase activity even at concentration 500 times higher than their IC50 values against gastric H+,K+-ATPase activity. TAK-438 inhibits gastric H+, K+-ATPase in a K+-competitive manner with Ki of 3 nM [2]. in vivo: TAK-438 inhibits basal gastric acid secretion in a dose-dependent manner, and the ID50 value is 1.26 mg/kg . Intravenous administration of TAK-438 dose-dependently increases the pH of the gastric perfusate, and the increase in pH is sustained for 5 h after administration. At the 1 mg/kg dose, the pH plateaues 90 min after administration, and the highest pH value reached is 5.9 [2]. In addition, TAK-438 shows a potent and longer-lasting inhibitory effect on the histamine-stimulated gastric acid secretion in rats and dogs. TAK-438 shows significant antisecretory activity through high accumulation and slow clearance from the gastric tissue. TAK-438 is unaffected by the gastric secretory state, unlike PPIs [3].

Clinical Trial

NCT02141711

Takeda

Erosive Esophagitis(EE)-Gastroesophageal Reflux Disease (GERD)

October 2008

Phase 1

NCT02774902

Takeda

Healthy Volunteers

August 2010

Phase 1

NCT03085836

Takeda

Healthy Participants

April 25, 2017

Phase 1

NCT01452776

Takeda

Erosive Esophagitis

September 2011

Phase 3

NCT02123953

Takeda

Dose Finding Study

October 2008

Phase 1

NCT02123927

Takeda

Ascending Single Dose Study

September 2007

Phase 1

NCT02954848

Takeda

Non-erosive Gastroesophageal Reflux Disease

December 1, 2016

Phase 3

NCT01459367

Takeda

Erosive Esophagitis

October 2011

Phase 3

NCT02141698

Takeda-Richmond Pharmacology Limited

Dose Finding Study

October 2007

Phase 1

NCT02892409

Takeda

Helicobacter Pylori

September 21, 2016

Phase 1

NCT01474369

Takeda

Non-erosive Gastroesophageal Reflux Disease

December 2011

Phase 3

NCT01505127

Takeda

H. Pylori Infection

January 2012

Phase 3

NCT01452698

Takeda

Erosive Esophagitis

Phase 3

NCT01452711

Takeda

Gastric Ulcer

November 2011

Phase 3

NCT03050307

Takeda

Gastric Ulcer-Peptic Ulcer-Gastrointestinal Diseases-Digestive System Diseases-Lansoprazole-Anti-Ulcer Agents-Gastrointestinal Agents-Proton Pump Inhibitors-Enzyme Inhibitors-Molecular Mechanisms of Pharmacological Action

April 17, 2017

Phase 3

NCT03050359

Takeda

Duodenal Ulcer

April 4, 2017

Phase 3

NCT01452724

Takeda

Duodenal Ulcer

October 2011

Phase 3

NCT01568398

Takeda

Gastric Ulcer-Duodenal Ulcer

May 2012

Phase 3

NCT01568385

Takeda

Gastric Ulcer-Duodenal Ulcer

April 2012

Phase 3

NCT01452763

Takeda

Gastric Ulcers-Duodenal Ulcers

October 2011

Phase 3

NCT01456247

Takeda

Gastric Ulcers-Duodenal Ulcers

March 2012

Phase 3

NCT01452750

Takeda

Gastric Ulcers-Duodenal Ulcers

October 2011

Phase 3

NCT01456260

Takeda

Gastric Ulcers-Duodenal Ulcers

September 2011

Phase 3

NCT01630746

Takeda

Erosive Esophagitis

July 2012

Phase 3

NCT03116841

Takeda

Reflux Esophagitis

April 21, 2017

Phase 4

NCT02679508

Takeda

Erosive Esophagitis

March 29, 2016

Phase 4

NCT02743949

Takeda

Gastroesophageal Reflux

July 14, 2016

Phase 2

NCT03214198

Takeda

A History of Gastric or Duodenal Ulcers

September 1, 2016

NCT03214094

Takeda

Gastric or Duodenal Ulcers

September 1, 2016

NCT03214952

Takeda

Gastric Ulcer, Duodenal Ulcer, and Reflux Esophagitis

March 1, 2016

NCT03214081

Takeda

Reflux Esophagitis

March 1, 2016

NCT02827942

Hamamatsu University

Gastritis Associated With Helicobacter Pylori

July 2016

Phase 3

NCT02388724

Takeda

Erosive Esophagitis

March 16, 2015

Phase 3

NCT02388737

Takeda

Erosive Esophagitis

April 2015

Phase 3

NCT02037477

Takeda

Healthy Volunteers

January 2014

Phase 3

NCT03219723

Takeda

Gastric/Duodenal Ulcer, Gastric MALT Lymphoma, Idiopathic Thrombocytopenic Purpura, or H. Pylori Gastritis, and Other

September 1, 2015

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References

[1].Arikawa Y, et al. Discovery of a novel pyrrole derivative 1-[5-(2-fluorophenyl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrol-3-yl]-N-methylmethanamine fumarate (TAK-438) as a potassium-competitive acid blocker (P-CAB). J Med Chem, 2012, 55(9), 4446-4456.

[2].Hori Y, et al. 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. J Pharmacol Exp Ther, 2010, 335(1), 231-238.

[3].Hori Y, et al. A study comparing the antisecretory effect of TAK-438, a novel potassium-competitive acid blocker, with lansoprazole in animals. J Pharmacol Exp Ther, 2011, 337(3), 797-804.

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