A positive allosteric modulator of the β1AR with antagonist activity for catecholaminergic polymorphic ventricular tachycardia.

ABSTRACT: Orthosteric β-blockers represent the leading pharmacological intervention for managing heart diseases owing to their ability to competitively antagonize β-adrenergic receptors (βARs). However, their use is often limited by the development of adverse effects such as fatigue, hypotension, and reduced exercise capacity, due in part to the nonselective inhibition of multiple βAR subtypes. These challenges are particularly problematic in treating catecholaminergic polymorphic ventricular tachycardia (CPVT), a disease characterized by lethal tachyarrhythmias directly triggered by cardiac β1AR activation. To identify small molecule allosteric modulators of the β1AR that could offer enhanced subtype specificity and robust functional antagonism of β1AR-mediated signaling, we conducted a DNA-encoded

SUBMITTER: Grogan A 

PROVIDER: S-EPMC12700548 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature