Compound 11

Compound 11 (C11) is a novel, selective small molecule identified as a positive allosteric modulator antagonist (PAMA) of the beta-1 adrenergic receptor (β1AR). Discovered through a DNA-encoded small-molecule library screen, it represents an emerging class of allosteric modulators that positively influence orthosteric agonist binding affinity while simultaneously blocking downstream signaling and functional receptor activation. This mechanism provides robust functional antagonism of β1AR-mediated signaling with high subtype specificity, potentially overcoming the clinical limitations of traditional orthosteric beta-blockers, such as fatigue and hypotension caused by nonselective inhibition. Compound 11 has demonstrated efficacy in preventing agonist-induced spontaneous contractile activity and exercise-induced ventricular tachycardia in murine models of catecholaminergic polymorphic ventricular tachycardia (CPVT), making it a promising therapeutic candidate for cardiac diseases characterized by excessive β1AR activation.

Other names

C11C-11C 11