ArticleJournal of molecular and cellular cardiology2016
Probing the mechanism of cardiovascular drugs using a covalent levosimendan analog.
Article in Journal of molecular and cellular cardiology, 2016. 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, 17 citations in OpenAlex.
- Integrative Methods for Studying Cardiac Energetics.Methods in molecular biology (Clifton, N.J.) · 2021Article
- Discovery of Novel Small-Molecule Calcium Sensitizers for Cardiac Troponin C: A Combined Virtual and Experimental Screening Approach.Journal of chemical information and modeling · 2020Article
- Levosimendan Efficacy and Safety: 20 Years of SIMDAX in Clinical Use.Journal of cardiovascular pharmacology · 2020Review
- Levosimendan Efficacy and Safety: 20 years of SIMDAX in Clinical Use.Cardiac failure review · 2020Review
- Optimizing fluorine labelling forJournal of biomolecular NMR · 2020Article
- Mechanism of Cardiac Troponin C Calcium Sensitivity Modulation by Small Molecules Illuminated by Umbrella Sampling Simulations.Journal of chemical information and modeling · 2019Article
- Thioimidate Bond Formation between Cardiac Troponin C and Nitrile-containing Compounds.ACS medicinal chemistry letters · 2019Article
- Article
- Dynamic Equilibrium of Cardiac Troponin C's Hydrophobic Cleft and Its Modulation by CaBioconjugate chemistry · 2017Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
One approach to improve contraction in the failing heart is the administration of calcium (Ca(2+)) sensitizers. Although it is known that levosimendan and other sensitizers bind to troponin C (cTnC), their in vivo mechanism is not fully understood. Based on levosimendan, we designed a covalent Ca(2+) sensitizer (i9) that targets C84 of cTnC and exchanged this complex into cardiac muscle. The NMR structure of the covalent complex showed that i9 binds deep in the hydrophobic pocket of cTnC. Despite slightly reducing troponin I affinity, i9 enhanced the Ca(2+) sensitivity of cardiac muscle. We conclude that i9 enhances Ca(2+) sensitivity by stabilizing the open conformation of cTnC. These findings provide new insights into the in vivo mechanism of Ca(2+) sensitization and demonstrate that directly targeting cTnC has significant potential in cardiovascular therapy.
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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.