vonoprazan   Click here for help

GtoPdb Ligand ID: 11549

Synonyms: compound 13e [PMID: 22512618] | TAK-438 | TAK438 | Takecab® | TAKECAB® | Vocinti® | Voquezna®
Approved drug PDB Ligand
vonoprazan is an approved drug (Japan (2014), FDA (2022))
Compound class: Synthetic organic
Comment: Vonoprazan (TAK-438) is a first-in-class, potassium competitive acid blocker (P-CAB) class agent [4,7]. It reduces gastric acid production via reversible inhibition of the gastric proton pump ATPase (a.k.a. gastric H+,K+-ATPase) [1-2,7]. The compound appears to dock within the luminal vestibule of the proton pump's alpha subunit (ATP4A) and prevents K+ access to the ion binding domain, with a Ki of 3 nM for the wild type H+,K+-ATPase [7]. Vonoprazan has a faster onset of action than widely used proton pump inhibitors (PPI), doesn't require acid-mediated activation and provides long-lasting inhibition (due to its slow dissociation rate) of the gastric H+,K+-ATPase [5-6].
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 4
Hydrogen bond donors 1
Rotatable bonds 5
Topological polar surface area 72.37
Molecular weight 345.09
XLogP 2.5
No. Lipinski's rules broken 0
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Canonical SMILES CNCc1cc(n(c1)S(=O)(=O)c1cccnc1)c1ccccc1F
Isomeric SMILES CNCc1cc(n(c1)S(=O)(=O)c1cccnc1)c1ccccc1F
InChI InChI=1S/C17H16FN3O2S/c1-19-10-13-9-17(15-6-2-3-7-16(15)18)21(12-13)24(22,23)14-5-4-8-20-11-14/h2-9,11-12,19H,10H2,1H3
1. Abe K, Irie K, Nakanishi H, Suzuki H, Fujiyoshi Y. (2018)
Crystal structures of the gastric proton pump.
Nature, 556 (7700): 214-218. [PMID:29618813]
2. Arikawa Y, Nishida H, Kurasawa O, Hasuoka A, Hirase K, Inatomi N, Hori Y, Matsukawa J, Imanishi A, Kondo M et al.. (2012)
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, 55 (9): 4446-56. [PMID:22512618]
3. Garnock-Jones KP. (2015)
Vonoprazan: first global approval.
Drugs, 75 (4): 439-43. [PMID:25744862]
4. Inatomi N, Matsukawa J, Sakurai Y, Otake K. (2016)
Potassium-competitive acid blockers: Advanced therapeutic option for acid-related diseases.
Pharmacol Ther, 168: 12-22. [PMID:27514776]
5. Oshima T, Miwa H. (2018)
Potent Potassium-competitive Acid Blockers: A New Era for the Treatment of Acid-related Diseases.
J Neurogastroenterol Motil, 24 (3): 334-344. [PMID:29739175]
6. Otake K, Sakurai Y, Nishida H, Fukui H, Tagawa Y, Yamasaki H, Karashima M, Otsuka K, Inatomi N. (2016)
Characteristics of the Novel Potassium-Competitive Acid Blocker Vonoprazan Fumarate (TAK-438).
Adv Ther, 33 (7): 1140-57. [PMID:27287852]
7. Scott DR, Munson KB, Marcus EA, Lambrecht NW, Sachs G. (2015)
The binding selectivity of vonoprazan (TAK-438) to the gastric H+, K+ -ATPase.
Aliment Pharmacol Ther, 42 (11-12): 1315-26. [PMID:26423447]