AGI-101

AGI-101 is a first-in-class small molecule inhibitor of phosphodiesterase 2A (PDE2A) being developed by Agiana Pharmaceuticals for the treatment of catecholaminergic polymorphic ventricular tachycardia (CPVT) and heart failure. PDE2A is a dual-specificity enzyme that hydrolyzes both cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP); it is uniquely regulated by cGMP, which binds to an allosteric GAF-B domain to stimulate cAMP hydrolysis. In cardiac myocytes, PDE2A is localized to key signaling microdomains, including those involving the ryanodine receptor (RyR2). In CPVT, mutations in RyR2 lead to diastolic calcium leaks and triggered activity. AGI-101 aims to restore cyclic nucleotide balance and stabilize calcium release from the sarcoplasmic reticulum, thereby preventing the life-threatening ventricular arrhythmias characteristic of the disease. The compound is currently in early-stage development.

Other names

PDE2 inhibitorPDE-2 inhibitorPDE 2 inhibitorPDE2A inhibitorPDE-2A inhibitorPDE 2A inhibitorPhosphodiesterase 2 inhibitorPhosphodiesterase2 inhibitorPhosphodiesterase-2 inhibitorPhosphodiesterase 2A inhibitorPhosphodiesterase2A inhibitorPhosphodiesterase-2A inhibitor