PDE4-IN-34

PDE4-IN-34 is a phosphodiesterase 4 (PDE4) inhibitor with IC50 values of 19 pM for PDE4B1 and 14 pM for PDE4D2. It exhibits weak inhibitory activity against PDE8A1 with an IC50 of 4.092 μM, showing significant selectivity for other subtypes (IC50 > 10 μM). In a rat model induced by cigarette smoke and LPS, PDE4-IN-34 improves lung function, reduces inflammation, and alleviates lung tissue damage. This compound is applicable in research related to chronic obstructive pulmonary disease.

PDE4B1:19 pM

PDE4-IN-34 (Compound P29) demonstrates potent inhibition of TNF-α release from LPS-induced human peripheral blood mononuclear cells (PBMCs) with an IC50 of 0.3 nM across concentrations of 1 fM to 1 µM over 18 hours. At 1 μM, PDE4-IN-34 binds to 99.5% of human plasma proteins over 6 hours. In human liver microsomes, it metabolizes with a hepatic clearance rate of 0.0522 mL/min/mg and a half-life of 26.6 minutes. PDE4-IN-34 does not significantly inhibit the hERG potassium channel up to 30 μM, suggesting a low risk of cardiotoxicity. Furthermore, it shows no significant inhibition of human liver enzymes CYP1A2, CYP2C9, CYP2C19, CYP2D6, or CYP3A4 up to 10 μM, indicating a low potential for drug-drug interactions.

PDE4-IN-34 (Compound P29), administered via tracheal route at doses of 0.1-3 μmol/kg daily for 28 days, effectively alleviates cigarette smoke and LPS-induced COPD in rats by inhibiting the activity of inflammatory cells and cytokine release in a dose-dependent manner. Additionally, PDE4-IN-34, when administered as a single dose via tracheal route at 3-10 mg/kg, does not induce vomiting in Beagle dogs even at inhalation doses up to 10 mg/kg.