pde4d

Oglemilast (GRC 3886) suppresses pulmonary cell infiltration, including eosinophilia and neutrophilia in vitro and in vivo. Oglemilast is an effective and orally active phosphodiesterase-4 (PDE4) inhibitor (IC50: 0.5 nM for PDE4D3). Oglemilast has the potential for inflammatory airway diseases.

ADORA2A PDE4D-IN-1 (Compound 9) is a dual inhibitor of the adenosine A2a receptor (ADORA2A) and phosphodiesterase 4D (PDE4D). This compound is applicable for research in bronchial asthma.

PDE4-IN-1 is a PDE4 inhibitor characterized by high potency (IC50: 8.6 nM) and superior selectivity over other PDE subtypes. This compound inhibits the release of inflammatory cytokines and chemokines. Additionally, PDE4-IN-1 significantly restores the damaged cAMP-CREB signaling pathway, inhibits proliferation, and promotes differentiation to reverse psoriasis formation.

Rolipram (SB 95952) is a phosphodiesterase 4 inhibitor with antidepressant properties.

Zatolmilast (BPN14770) is an allosteric inhibitor of selective phosphodiesterase 4D (PDE4D; IC50s: 7.8 nM and 7.4 nM for PDE4D7 and PDE4D3).

PDE2 PDE10-IN-1 is an inhibitor of phosphodiesterase 2 (PDE2) and PDE10, with IC50 values of 29 nM and 480 nM, respectively.

Compound 4p (PDE4B D-IN-4) is an effective inhibitor of PDE-4B and PDE-4D, with IC50 values of 5.50 nM and 6.81 nM respectively. Following the administration of PDE4B D-IN-4, intracellular cAMP levels are elevated.

PDE1-IN-8 (Compound 3f) acts as an inhibitor of PDE1, with an IC50 of 11 nM. It hinders cAMP and cGMP signaling pathways, impeding the differentiation and proliferation of cells into myofibroblasts, and demonstrates antifibrotic effects in the Bleomycin-induced rat model of pulmonary fibrosis.

PDE4-IN-24 (compound 14h) is a potent inhibitor of PDE4D with an IC50 value of 0.57 nM and exhibits over 4100-fold selectivity compared to other PDE families. It plays a significant role in the treatment of inflammatory diseases.

PDE4-IN-26 (Compound A5) is an orally active, highly selective inhibitor of PDE4. It exhibits anti-inflammatory properties by inhibiting p38 MAPK phosphorylation. In mouse models of acute lung injury and chronic obstructive pulmonary disease, PDE4-IN-26 reduces lung inflammation, damage, and fibrosis, while promoting sputum secretion and alleviating cough. It is useful for researching lung injury-related diseases.

Apremilast, (+/-)-, is a small molecule inhibitor of phosphodiesterase 4 (PDE4) with oral activity. It is used to treat psoriatic arthritis.

GSK356278 is an effective and selective inhibitor of phosphodiesterase 4 (PDE4), with pIC50s of 8.6, 8.8, and 8.7 for human PDE4A, PDE4B, and PDE4D, respectively. GSK356278 has anti-inflammatory, anxiolytic, and cognition-enhancing effects.

PF-06445974 has good selectivity for PDE4D, excellent brain permeability, and has a high level of specific binding in the cold tracer study.

PDE4B-IN-2 (A 33) is an orally active and selective PDE4B inhibitor with an IC50 of 15 nM. PDE4B-IN-2 inhibits PDE4D (IC50=1.7 µM). PDE4B-IN-2 exhibits potent anti-inflammatory effects.

LEO 39652, a dual-soft PDE4 inhibitor, demonstrates potent inhibition of PDE4 subtypes A, B, C, and D with respective IC50 values of 1.2 nM, 1.2 nM, 3.0 nM, and 3.8 nM. Additionally, it inhibits TNF-α with an IC50 of 6.0 nM, indicating its potential for topical Atopic dermatitis (AD) research [1].

D159687 is a selective PDE4D inhibitor,had a procognitive profile as it improved memory in the novel object recognition test but had no antidepressant or anxiolytic benefit.

AChE PDE4-IN-1 (compound 12c) is a highly effective and specific dual inhibitor of PDE4 and AChE, with IC50 values of 0.28 μM for AChE and 1.88 μM for PDE4D. This compound shows notable potential in reducing neuroinflammation associated with Alzheimer's disease research [1].

LASSBio-1632 is a novel anti-asthmatic lead candidate that selectively inhibits PDE4A and PDE4D isoenzymes, leading to the suppression of airway hyper-reactivity (AHR) and TNF-α production in lung tissue. With high experimental BBB permeability, LASSBio-1632 (7j) efficiently crosses the blood-brain barrier through passive diffusion [1].

PDE4-IN-6 is a safe, potent and moderately selective inhibitor of PDE4, acting on PDE4B (IC50: 0.125 μM) and PDE4D (IC50: 0.43 μM). PDE4-IN-6 is able to down-regulate TNF-α and IL-6 expression levels, exhibits anti-inflammatory and anti-arthritic effects, and has potent immunomodulatory activity. PDE4-IN-6 has potential for anti-rheumatoid arthritis studies.

mTOR inhibitor-11 (Compound 9) is a brain-penetrant compound that inhibits mTOR with an IC50 of 21 nM for pS6 and exhibits inhibitory activity against pCHK1 and PDE4D with IC50 values of 17.2 μM and 17.0 μM, respectively. This compound is utilized in CNS disease research [1].

PDE4B D-IN-2 (example 19) serves as a highly effective inhibitor of PDE4, exhibiting IC50 values of 0.023 nM for PDE4B2 and 0.066 nM for PDE4D.

PDE4B/D-IN-1 (example 8), a potent inhibitor of PDE4B, demonstrates inhibitory effects with IC50 values of 0.07 nM for PDE4B2 and 0.09 nM for PDE4D, respectively.

PDE4B D-IN-3 (example 22) is an effective inhibitor targeting PDE4, exhibiting IC50 values of 0.071 nM for PDE4B2 and 0.09 nM for PDE4D, respectively.

Z21115 is an orally effective phosphodiesterase 4 (PDE4) inhibitor that can inhibit PDE4D7 with an IC50 of 10.5 nM. It suppresses the expression of IL-6, TNF-α, and iNOS induced by Lipopolysaccharide. In a DSS-induced mouse colitis model, Z21115 demonstrates anti-inflammatory activity without significant toxicity at doses up to 1 g kg.