PDE/TRPA1/CHIT1-IN-1 is an inhibitor of PDEs, TRPA1, and hCHIT1 with a KD value of 37.7 μM. It acts as a broad-spectrum PDE inhibitor, effectively targeting key subtypes including PDE4B, PDE7A, PDE3A, and PDE8A with IC50 values of 15.54, 15.15, 8.39, and 16.46 μM, respectively. By inhibiting NLRP3 inflammasome activation and blocking NF-κB phosphorylation, PDE/TRPA1/CHIT1-IN-1 downregulates the expression of pro-inflammatory genes (TNF-α and IL-6) in vivo. This compound is useful for research into chronic obstructive pulmonary disease (COPD) and related inflammatory lung conditions.

PDE4B:15.54 μM

PDE/TRPA1/CHIT1-IN-1 (compound 39) demonstrates anti-inflammatory properties in Lipopolysaccharides (LPS)-stimulated RAW264.7 macrophages at a concentration of 10 μM for 1 hour. This compound inhibits multiple phosphodiesterases, including PDE1B, PDE2A, PDE4B, PDE7A, PDE3A, PDE4D, PDE5A, PDE8A, and PDE10A, with respective IC50 values of 54.47, 79.61, 15.54, 15.15, 8.39, 130.50, 26.86, 16.46, and 36.13 μM. At concentrations ranging from 1 to 50 μM for 1 hour, it inhibits bronchial smooth muscle cell proliferation and hypertrophy, reduces the secretion of extracellular matrix components in BSMC and MRC-5 cells, and suppresses fibroblast-to-myofibroblast transformation. Additionally, PDE/TRPA1/CHIT1-IN-1 exhibits a bronchodilatory effect with an IC50 of 1.56 μM, achieving a maximum relaxation rate of 100% in pre-contracted rat tracheal rings. The compound also shows high metabolic stability (t 1/2 = 53.42 minutes, intrinsic clearance Cl int = 32.43 μL/min/mg), negligible hepatotoxicity (IC50 = 34.70 μM in HepG2 cells), and moderate membrane permeability (logPe = -5.305).

PDE/TRPA1/CHIT1-IN-1 (compound 39) (25 mg/kg, administered intraperitoneally once daily for 2 weeks) exhibited anti-inflammatory properties and regulated the NLRP3 inflammasome in an elastase-induced emphysema model.