PDE5-IN-1

PDE5-IN-1 (compound 2) is a PDE5 inhibitor with an IC₅₀ of 5.6 nM and oral bioavailability. PDE5-IN-1 forms hydrogen bond interactions with the Q817 residue in the catalytic domain of PDE5, and aromatic π-π stacking interactions with the F820 residue. PDE5-IN-1 exerts anti-cardiac hypertrophy and vasodilatory effects, reduces mean pulmonary arterial pressure and right ventricular hypertrophy index. PDE5-IN-1 can be used in the research of pulmonary arterial hypertension^[1]. In Vitro:PDE5-IN-1 (compound 2) (multiple concentrations; 15 min) potently inhibits the PDE5A catalytic domain with an IC₅₀ of 5.6 nM^[1].
PDE5-IN-1 (multiple concentrations; 15 min) shows remarkable selectivity for PDE5A over other PDE families, with selectivity indices ranging from 10 (vs PDE6A) to >1700 (vs PDE1B, PDE3A, PDE7A1, PDE9A2)^[1].
PDE5-IN-1 (multiple concentrations) has weak inhibitory effects on major human hepatic CYP isoenzymes, with only moderate inhibition of CYP1A2 (IC₅₀ = 7.6 μM) and no significant inhibition of six other key isoenzymes^[1].
PDE5-IN-1 (multiple concentrations) shows weak inhibition of the hERG potassium channel, with an IC₅₀ >10 μM^[1].
PDE5-IN-1 (0.5 μM; incubated to determine T_1/2) is stable in both rat and human liver microsomes, with significantly longer half-lives than the positive control midazolam^[1]. In Vivo:PDE5-IN-1 (compound 2) (5.0 mg/kg; p.o.; daily; 3 weeks) produces a statistically significant reduction in mPAP and RVHI in MCT-induced PAH rats, with superior efficacy to sildenafil citrate at 10.0 mg/kg^[1].