ArticleJournal of medicinal chemistry2020
Molecular Basis for Omapatrilat and Sampatrilat Binding to Neprilysin-Implications for Dual Inhibitor Design with Angiotensin-Converting Enzyme.
Article in Journal of medicinal chemistry, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
9 citing papers in PubMed, 22 citations in OpenAlex.
- MBind: A Web-Based Platform for Metalloprotein and Nonmetalloprotein Docking with Optional ML Docking Integration.Molecules (Basel, Switzerland) · 2026Article
- Design of Novel Mercapto-3-phenylpropanoyl Dipeptides as Dual Angiotensin-Converting Enzyme C-Domain-Selective/Neprilysin Inhibitors.Journal of medicinal chemistry · 2025Article
- Advances in the structural basis for angiotensin-1 converting enzyme (ACE) inhibitors.Bioscience reports · 2024Review
- Comprehensive review on neprilysin (NEP) inhibitors: design, structure-activity relationships, and clinical applications.Frontiers in pharmacology · 2024Review
- Is It Still Relevant to Discover New ACE Inhibitors from Natural Products? YES, but Only with Comprehensive Approaches to Address the Patients' Real Problems: Chronic Dry Cough and Angioedema.Molecules (Basel, Switzerland) · 2023Review
- Small molecule angiotensin converting enzyme inhibitors: A medicinal chemistry perspective.Frontiers in pharmacology · 2022Review
- Exploring the Impact of ACE Inhibition in Immunity and Disease.Journal of the renin-angiotensin-aldosterone system : JRAAS · 2022Review
- PDE-Mediated Cyclic Nucleotide Compartmentation in Vascular Smooth Muscle Cells: From Basic to a Clinical Perspective.Journal of cardiovascular development and disease · 2021Review
- In Vitro Modeling of Bradykinin-Mediated Angioedema States.Pharmaceuticals (Basel, Switzerland) · 2020Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
Neprilysin (NEP) and angiotensin-converting enzyme (ACE) are two key zinc-dependent metallopeptidases in the natriuretic peptide and kinin systems and renin-angiotensin-aldosterone system, respectively. They play an important role in blood pressure regulation and reducing the risk of heart failure. Vasopeptidase inhibitors omapatrilat and sampatrilat possess dual activity against these enzymes by blocking the ACE-dependent conversion of angiotensin I to the potent vasoconstrictor angiotensin II while simultaneously halting the NEP-dependent degradation of vasodilator atrial natriuretic peptide. Here, we report crystal structures of omapatrilat, sampatrilat, and sampatrilat-ASP (a sampatrilat analogue) in complex with NEP at 1.75, 2.65, and 2.6 Å, respectively. A detailed analysis of these structures and the corresponding structures of ACE with these inhibitors has provided the molecular basis of dual inhibitor recognition involving the catalytic site in both enzymes. This new information will be very useful in the design of safer and more selective vasopeptidase inhibitors of NEP and ACE for effective treatment in hypertension and heart failure.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.