ArticleACS medicinal chemistry letters2023
Conversion of a Cardiac Muscle Modulator from an Inhibitor to an Activator.
Article in ACS medicinal chemistry letters, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
2 citing papers in PubMed, 3 citations in OpenAlex.
- Emerging Concepts of Mechanisms Controlling Cardiac Tension: Focus on Familial Dilated Cardiomyopathy (DCM) and Sarcomere-Directed Therapies.Biomedicines · 2024Review
- Synthesis and Biophysical Characterization of Fingolimod Derivatives as Cardiac Troponin Antagonists.ACS medicinal chemistry letters · 2024Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
The binding of calcium to cardiac troponin C (cTnC) enhances the binding of troponin I (cTnI) switch region to the regulatory domain of cTnC (cNTnC) and triggers muscle contraction. Several molecules alter the response of the sarcomere by targeting this interface; virtually all have an aromatic core that binds to the hydrophobic pocket of cNTnC and an aliphatic tail that interacts with the switch region of cTnI. W7 has been extensively studied, and the positively charged tail has been shown to be important for its inhibitory action. Herein we investigate the importance of the aromatic core of W7 by synthesizing compounds that have the core region of calcium activator dfbp-o with various lengths of the same tail (D-series). These compounds all bind more tightly to cNTnC-cTnI chimera (cChimera) than the analogous W-series compounds and show increased calcium sensitivity of force generation and ATPase activity, demonstrating that the cardiovascular system is tightly balanced.
Identifiers
What OpenQuestion holds
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.