β1AR antagonist Compound 11 (β1AR PAM antagonist C11) is a selective, allosteric modulator of β1-adrenergic receptor (β1AR) and PAM antagonist, selectively potentiates the binding affinity of orthosteric agonists to the β1AR while potently inhibiting downstream signaling following β1AR activation.
C11 potentiates the binding affinity of agonists and a subset of antagonists to the β1AR.
C11 suppresses G protein and β-arrestin signaling downstream of agonist-activated β1AR.
C11 acts as an unbiased functional NAM of agonist-activated β1AR since it potently inhibits both Gs and β-arrestin signaling.
C11 is highly selective for β1ARs over alternative GPCRs of the cardiovascular system including the β2AR, AT1R, and M3R.
C11 reduces basal contractility and suppresses the isoproterenol response in isolated wild type cardiomyocytes.
C11 restores regular contractile rhythm and suppresses spontaneous Ca2+ release in CSQ2 /- cardiomyocytes.
C11 (10 mg/kg) suppresses exercise-induced ventricular tachycardia in vivo.