Key result
TRPV4 antagonist Compound 26 suppresses fibrosis and improves cardiac function in organoid and murine models.
Why the study?
Cardiac fibrosis drives adverse ventricular remodeling and progression to heart failure, but small-molecule therapies targeting mechanosensitive profibrotic signaling remain challenging.
Does compound 26 improve cardiac function and attenuate adverse remodeling in preclinical models of cardiac fibrosis?
Does compound 26 improve cardiac function and attenuate adverse remodeling in preclinical models of cardiac fibrosis?
Compound 26, a novel TRPV4 antagonist, demonstrates anti-fibrotic efficacy in 3D myocardial organoids and improves cardiac function in a murine pressure-overload model, highlighting its potential as a therapeutic candidate for cardiac fibrosis.
Answers are grounded in this paper and cite their sources.
Supports TRPV4 antagonism in preclinical fibrosis; hypothesis-generating and should not change practice.
Cardiac fibrosis drives adverse ventricular remodeling and progression to heart failure, yet small-molecule therapies targeting mechanosensitive profibrotic signaling remain challenging. Herein, starting from our reported vicinal-diol TRPV4 antagonist AH001, we performed structure-guided optimization to generate a focused series of active analogues. A single-point TRPV4 Ca2+ influx assay (5 μM) was used for rapid screening and SAR analysis, followed by tissue-level validation in oxygen–glucose deprivation (OGD)-induced 3D myocardial organoids. Compound 26 markedly suppressed fibrosis-associated phenotypes in this organoid model, with a phenotypic IC50 of 6.45 μM. In vivo, compound 26 improved cardiac function and attenuated adverse remodeling in a murine transverse aortic constriction (TAC) pressure-overload model. Together, these findings support compound 26 as a promising candidate for the treatment of cardiac fibrosis.
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Chen et al. (2026) studied Cardiac fibrosis. Compound 26 was evaluated on Fibrosis-associated phenotypes and cardiac function/remodeling (IC50 6.45 μM). Compound 26, a novel TRPV4 antagonist, suppressed fibrosis-associated phenotypes in a 3D myocardial organoid model and improved cardiac function in a murine pressure-overload model.
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