Key result
High-throughput screening of 2,684 FDA-approved compounds identified 60 hits that modulate the interaction between cardiac myosin-binding protein C and actin or bind directly to cC0-C2.
Why the study?
Phosphorylation of cMyBP-C is often decreased in heart failure patients and cardioprotective in model systems, making it a potential target for drugs that mimic phosphorylation or perturb interactions with actin or myosin.
Population
FDA-approved drug library tested against labeled actin and cMyBP-C C0-C2 fragments
Design
In vitro high-throughput screening study
Authors
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Hits require validation in heart failure models; leaves open therapeutic translation.
This high-throughput screening approach successfully identified FDA-approved small molecules that specifically modulate cardiac myosin-binding protein C, providing potential starting points for novel heart failure therapeutics.
Bunch et al. (2023) studied Heart failure (n=2,684). FDA-approved compounds vs. DMSO control was evaluated on Change in fluorescence lifetime (FLT) > 4 SD relative to control. High-throughput screening of 2,684 FDA-approved compounds identified 60 hits that modulate the interaction between cardiac myosin-binding protein C and actin or bind directly to cC0-C2.
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