New drugs to suppress acid secretion: current and future developments

Scarpignato, Carmelo

doi:10.1016/j.ddstr.2007.09.003

Cited by 9 publications

(9 citation statements)

References 28 publications

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“…This pharmacological phenomenon results in a decline in acid suppression that limits the regular use of H2RAs in clinical practice [23,24]. Thus, it is still unknown if the new H 2 RAs have a similar limitation.…”

Section: Lavoltidine (Ah234844)mentioning

confidence: 97%

Novel Upcoming Therapies

Maradey–Romero

Fass

2015

Diagnosis and Treatment of Gastroesophageal Reflux Disease

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Section: Lavoltidine (Ah234844)mentioning

confidence: 97%

Novel Upcoming Therapies

Maradey–Romero

Fass

2015

Diagnosis and Treatment of Gastroesophageal Reflux Disease

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“…This pharmacological phenomenon results in a decline in acid suppression that limits the regular use of H2RAs in clinical practice 29,30. Thus, it is still unknown if the new H2RAs have a similar limitation.…”

Section: Histamine Type 2 Receptor Antagonistsmentioning

confidence: 99%

New and Future Drug Development for Gastroesophageal Reflux Disease

Maradey–Romero

Fass

2014

J Neurogastroenterol Motil

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Medical therapy remains the most popular treatment for gastroesophageal reflux disease (GERD). Whilst interest in drug development for GERD has declined over the last few years primarily due to the conversion of most proton pump inhibitor (PPI)'s to generic and over the counter compounds, there are still numerous areas of unmet needs in GERD. Drug development has been focused on potent histamine type 2 receptor antagonist's, extended release PPI's, PPI combination, potassium-competitive acid blockers, transient lower esophageal sphincter relaxation reducers, prokinetics, mucosal protectants and esophageal pain modulators. It is likely that the aforementioned compounds will be niched for specific areas of unmet need in GERD, rather than compete with the presently available anti-reflux therapies.

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“…H + ,K + -ATPase inhibitors include two classes: proton pump inhibitors (PPIs) and potassium-competitive acid blockers (P-CABs) [9] , [10] . PPIs such as omeprazole, lansoprazole, rabeprazole, pantoprazole, tenatoprazole and leminoprazole, are irreversible inhibitors of H + ,K + -ATPase, which form a covalent complex with the protein at specific cysteine residues [11] , [12] .…”

Section: Introductionmentioning

confidence: 99%

Protonated Form: The Potent Form of Potassium-Competitive Acid Blockers

Deng

Zou

2014

PLoS ONE

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Potassium-competitive acid blockers (P-CABs) are highly safe and active drugs targeting H+,K+-ATPase to cure acid-related gastric diseases. In this study, we for the first time investigate the interaction mechanism between the protonated form of P-CABs and human H+,K+-ATPase using homology modeling, molecular docking, molecular dynamics and binding free energy calculation methods. The results explain why P-CABs have higher activities with higher pKa values or at lower pH. With positive charge, the protonated forms of P-CABs have more competitive advantage to block potassium ion into luminal channel and to bind with H+,K+-ATPase via electrostatic interactions. The binding affinity of the protonated form is more favorable than that of the neutral P-CABs. In particular, Asp139 should be a very important binding site for the protonated form of P-CABs through hydrogen bonds and electrostatic interactions. These findings could promote the rational design of novel P-CABs.

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New drugs to suppress acid secretion: current and future developments

Cited by 9 publications

References 28 publications

Novel Upcoming Therapies

Novel Upcoming Therapies

New and Future Drug Development for Gastroesophageal Reflux Disease

Protonated Form: The Potent Form of Potassium-Competitive Acid Blockers

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