ArticleBritish journal of pharmacology2020
Discovery and characterization of ORM-11372, a novel inhibitor of the sodium-calcium exchanger with positive inotropic activity.
Article in British journal of pharmacology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 14 citations in OpenAlex.
- The NaThe Journal of veterinary medical science · 2026Review
- Pacemaking in the lymphatic system.The Journal of physiology · 2026Review
- D801N in ATP1A3-encoded Na/K-ATPase alpha 3 causes cardiac arrhythmogenesis through sodium-calcium exchanger-mediated calcium overload.JCI insight · 2026Article
- Druggability of Sodium Calcium Exchanger (NCX): Challenges and Recent Development.International journal of molecular sciences · 2025Review
- iPSC-cardiomyocytes in the preclinical prediction of candidate pharmaceutical toxicity.Frontiers in pharmacology · 2024Review
- Human induced pluripotent stem cell-derived cardiomyocytes as an electrophysiological model: Opportunities and challenges-The Hamburg perspective.Frontiers in physiology · 2023Review
- Antiarrhythmic and Inotropic Effects of Selective NaInternational journal of molecular sciences · 2022Review
- Regulation of APD and Force by the NaCells · 2022Article
- Arrhythmogenic and antiarrhythmic actions of late sustained sodium current in the adult human heart.Scientific reports · 2021Article
- Cardiotoxic Potential of Hydroxychloroquine, Chloroquine and Azithromycin in Adult Human Primary Cardiomyocytes.Toxicological sciences : an official journal of the Society of Toxicology · 2021Article
- Discovery and characterization of ORM-11372, a novel inhibitor of the sodium-calcium exchanger with positive inotropic activity.British journal of pharmacology · 2020Article
Corrections and comments
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Authors and funding
21 authors at 6 institutions in 3 countries.
Funding
Abstract
background and purposeThe lack of selective sodium-calcium exchanger (NCX) inhibitors has hampered the exploration of physiological and pathophysiological roles of cardiac NCX 1.1. We aimed to discover more potent and selective drug like NCX 1.1 inhibitor. EXPERIMENTAL APPROACH: A flavan series-based pharmacophore model was constructed. Virtual screening helped us identify a novel scaffold for NCX inhibition. A distinctively different NCX 1.1 inhibitor, ORM-11372, was discovered after lead optimization. Its potency against human and rat NCX 1.1 and selectivity against other ion channels was assessed. The cardiovascular effects of ORM-11372 were studied in normal and infarcted rats and rabbits. Human cardiac safety was studied ex vivo using human ventricular trabeculae. KEY
resultsORM-11372 inhibited human NCX 1.1 reverse and forward currents; IC CONCLUSION AND IMPLICATIONS: ORM-11372, a unique, novel, and potent inhibitor of human and rat NCX 1.1, is a positive inotropic compound. NCX inhibition can induce clinically relevant improvements in left ventricular contractions without affecting relaxation, heart rate, or BP, without pro-arrhythmic risk.
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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 OpenQuestion graph.