PDE8 Inhibitor

PDE4-IN-30 is a selective PDE4 inhibitor with an IC₅₀ of 2.7 nM for PED4D2, targeting PDE4 through halogen bonding and metal coordination. PDE4-IN-30 exhibits at least 67-fold selectivity for other PDE subfamilies. PDE4-IN-30 can be used for the research of idiopathic pulmonary fibrosis.

PDE4-IN-34 is a phosphodiesterase 4 (PDE4) inhibitor, with IC₅₀ values of 19 pM and 14 pM against PDE4B1 and PDE4D2, respectively. PDE4-IN-34 shows weak inhibitory activity against PDE8A1, with an IC₅₀ value of 4.092 μM, and exhibits significant selectivity over other subtypes (IC₅₀ > 10 μM). PDE4-IN-34 improves pulmonary function, reduces inflammatory responses and alleviates lung tissue damage in a rat model induced by cigarette smoke combined with LPS (HY-D1056). PDE4-IN-34 can be used for research related to chronic obstructive pulmonary disease.

PDE5-IN-13 (Compound 14b) inhibits phosphodiesterase 5 (PDE5A) with an IC₅₀ of 3 nM. PDE5-IN-13 is a potential candidate for PAH (pulmonary arterial hypertension) research. PDE5-IN-13 has high selectivity for targets over PDE1, PDE2, PDE3, PDE4, PDE7, PDE8, PDE9, PDE10, and PDE11. PDE5-IN-13 is orally active.

PDE4-IN-12 is a potent pan-PDE4 inhibitor, with IC₅₀s of 3.5 and 15 nM for PDE4 and PDE7, respectively (SI=2.71 and 4.27, respectively). PDE4-IN-12 shows well tolerated, can be used in study of inflammatory bowel diseases (IBDs).

Multitarget AD-IN-6 (Compound 39) is a multi-target inhibitor, with an IC₅₀ of 15.54 μM against PDE4B, 15.15 μM against PDE7A, 8.39 μM against PDE3A, and a K_d of 37.7 μM against CHIT1. Multitarget AD-IN-6 acts as a TRPA1 antagonist, reduces the level of the NLRP3 inflammasome multiprotein complex to inhibit its activation, while inhibiting PDE4B, PDE7A and CHIT1, and decreasing the phosphorylation of NF-κB. Multitarget AD-IN-6 improves the pathology of elastase-induced emphysema in mice. Multitarget AD-IN-6 is applicable for the research of chronic obstructive pulmonary disease.

PDE/TRPA1/CHIT1-IN-1 is a phosphodiesterases (PDEs), TRPA1, and hCHIT1 (K_D of 37.7 μM) inhibitor. PDE/TRPA1/CHIT1-IN-1 is a broad-spectrum PDE inhibitor, potently targeting key isoforms including PDE4B, PDE7A, PDE3A, and PDE8A with IC₅₀s of 15.54, 15.15, 8.39 and 16.46 μM. PDE/TRPA1/CHIT1-IN-1 suppresses NLRP3 inflammasome activation and inhibits NF-κB phosphorylation, downregulating the expression of pro-inflammatory genes (TNF-α and IL-6) in vivo. PDE/TRPA1/CHIT1-IN-1 can be used for chronic obstructive pulmonary disease (COPD) and related inflammatory lung disorders research.

BC8-15 is a PDE inhibitor with IC₅₀ values of 0.28, 0.22, and 6.46 µM for inhibiting PDE8A, PDE4A, and PDE7A, respectively. BC8-15 can enhance steroidogenesis in mouse Leydig cells.

LH17, a Kaempferol (HY-14590) derivative, is a potent and selective PDE4 inhibitor (PDE4D2 IC₅₀ = 73 nM, PDE4B2 IC₅₀ = 190 nM). LH17 exhibits remarkable selectivity (>136-fold) against other PDE isoforms (PDE1B/2A/3A/5A/8A/9A/10A) (IC₅₀ > 10000 nM), with the exception of PDE7A1 (IC₅₀ = 300 nM). LH17 distinctly interacts with PDE4 M-pocket. LH17 demonstrates remarkable anti-fibrotic efficacy in both in vitro and in vivo models. LH17 can be used for idiopathic pulmonary fibrosis (IPF) research.

PDE4-IN-1 is a PDE4 inhibitor with high potency (IC₅₀ : 8.6 nM) and selectivity over other PDE subtypes. PDE4-IN-1 inhibits the release of inflammatory cytokines and chemokines. PDE4-IN-1 greatly restores impaired cAMP-CREB signaling pathway. PDE4-IN-1 inhibits proliferation and promotes differentiation to reverse the formation of psoriasis.

PDE3/4-IN-4 is an orally active PDE3A and PDE4B inhibitor with IC₅₀ values of 10 nM and 9.4 nM, respectively. PDE3/4-IN-4 shows selective activity relative to most other PDE family members. PDE3/4-IN-4 modulates the cAMP/PKA/CREB signaling pathway. PDE3/4-IN-4 inhibits pro-inflammatory factor IL-6. PDE3/4-IN-4 reduces expression of inflammatory markers in liver tissue. PDE3/4-IN-4 attenuates liver fibrosis. PDE3/4-IN-4 limits liver damage in cholestatic and sepsis-induced liver disease mice models. PDE3/4-IN-4 can be used for the research of liver injury, cholestatic liver diseases, sepsis-induced liver injury.

PDE1-IN-8 (Compound 3f) is the inhibitor for PDE1 with an IC₅₀ of 11 nM. PDE1-IN-8 inhibits cAMP and cGMP signaling pathway, inhibits the differentiation and proliferation of cells into myofibroblast, and exhibits anti-fibrotic efficacy in Bleomycin (HY-17565)-induced rat pulmonary fibrosis model.