Basic Characteristics

Product Name	TAK-438
CAS Number	1260141-27-2
Molecular Formula	C21H20FN3O6S
Formula Weight	461.46
Synonyms	Vonoprazan Fumarate; TAK-438; 1260141-27-2; Vonoprazan fumurate; TAK438.
Appearance	White to off-white powder
Storage and Handling	Dry, dark and at 0 – 4 C for short term (days to weeks) or -20 C for long term (months to years).

 

TAK-438 Description

TAK438, also known as Vonoprazan Fumarate, is a new medicine for treating acid-related diseases with a novel mechanism of action called potassium-competitive acid blockers (P-CABs) which competitively inhibits the binding of potassium ions to H+,K+-ATPase (also known as the proton pump) in the final step of gastric acid secretion in gastric parietal cells, controls gastric acid secretion.  It provides a strong and sustained acid secretion inhibitory effect.

In cultured gastric glands, TAK-438 treatment resulted in a longer and stronger acid formation inhibition. The inhibition effect of TAK-438 on acid secretion seemed to be associated with gastric parietal cell physiology.

 

TAK-438 Mechanism of Action

TAK-438 (Vonoprazan fumarate) is a pyrole derivative and potassium-competitive acid blocker (P-CAB) that competitively blocks the potassium-binding site of gastric H(+),K(+)-ATPase, a key enzyme in the process of gastric acid secretion. The compound can accumulate in acid environments and should provide a longer duration of inhibition due to an alkaline pKa of 9.06.

In cultured gastric glands, TAK-438 treatment resulted in a longer and stronger acid formation inhibition. The inhibition effect of TAK-438 on acid secretion seemed to be associated with gastric parietal cell physiology.

 

TAK-438 Application

TAK-438 (Vonoprazan fumarate or Vonoprazan) is a new medicine for treating acid-related diseases with a novel mechanism of action called potassium-competitive acid blockers (P-CABs) which competitively inhibits the binding of potassium ions to H+,K+-ATPase (also known as the proton pump) in the final step of gastric acid secretion in gastric parietal cells. The drug is approved in Japan for the treatment of acid-related diseases, including gastric ulcer, duodenal ulcer, reflux esophagitis and Adjunct to Helicobacter pylori eradication in the case of Helicobacter pylori gastritis.

 

TAK-438 Side Effects & Warning

The common side effects included:

▪ diarrhoea,

▪ nausea and vomiting,

▪ constipation,

▪ abdominal pain,

▪ skin rash,

▪ heartburn.

 

These are not all the possible side effects of TAK438. For more information, ask your doctor or pharmacist. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

 

Reference

[1] Arikawa Y, Nishida H, Kurasawa O, Hasuoka A, Hirase K, Inatomi N, Hori Y, Matsukawa J, Imanishi A, Kondo M, Tarui N, Hamada T, Takagi T, Takeuchi T, Kajino M. Discovery of a novel pyrrole derivative 1-[5-(2-fluorophenyl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrol-3-yl]-N-methylmethanamin e fumarate (TAK-438) as a potassium-competitive acid blocker (P-CAB). J Med Chem. 2012 May 10;55(9):4446-56. doi: 10.1021/jm300318t. Epub 2012 Apr 30. PubMed PMID: 22512618.

[2] Kondo M, Kawamoto M, Hasuoka A, Kajino M, Inatomi N, Tarui N. High-throughput screening of potassium-competitive acid blockers. J Biomol Screen. 2012 Feb;17(2):177-82. doi: 10.1177/1087057111421004. Epub 2011 Sep 22. PubMed PMID: 21940711.

[3] Shin JM, Inatomi N, Munson K, Strugatsky D, Tokhtaeva E, Vagin O, Sachs G. Characterization of a novel potassium-competitive acid blocker of the gastric H,K-ATPase, 1-[5-(2-fluorophenyl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrol-3-yl]-N-methylmethanamin e monofumarate (TAK-438). J Pharmacol Exp Ther. 2011 Nov;339(2):412-20. doi: 10.1124/jpet.111.185314. Epub 2011 Aug 9. PubMed PMID: 21828261; PubMed Central PMCID: PMC3199995.

[4] Hori Y, Matsukawa J, Takeuchi T, Nishida H, Kajino M, Inatomi N. A study comparing the antisecretory effect of TAK-438, a novel potassium-competitive acid blocker, with lansoprazole in animals. J Pharmacol Exp Ther. 2011 Jun;337(3):797-804. doi: 10.1124/jpet.111.179556. Epub 2011 Mar 16. PubMed PMID: 21411494.

[5] Matsukawa J, Hori Y, Nishida H, Kajino M, Inatomi N. A comparative study on the modes of action of TAK-438, a novel potassium-competitive acid blocker, and lansoprazole in primary cultured rabbit gastric glands. Biochem Pharmacol. 2011 May 1;81(9):1145-51. doi: 10.1016/j.bcp.2011.02.009. Epub 2011 Mar 1. PubMed PMID: 21371447.

[6] Hori Y, Imanishi A, Matsukawa J, Tsukimi Y, Nishida H, Arikawa Y, Hirase K, Kajino M, Inatomi N. 1-[5-(2-Fluorophenyl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrol-3-yl]-N-methylmethanamin e monofumarate (TAK-438), a novel and potent potassium-competitive acid blocker for the treatment of acid-related diseases. J Pharmacol Exp Ther. 2010 Oct;335(1):231-8. doi: 10.1124/jpet.110.170274. Epub 2010 Jul 12. PubMed PMID: 20624992.

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