pde4b

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.

PDE4B-IN-3 is a potent PDE4B inhibitor (IC50: 0.94 μM) with anti-inflammatory effects.

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.

This compound is a dual 5-HT1A 5-HT7 receptor antagonist (5-HT1A Ki = 8 nM, Kb = 0.04 nM; 5-HT7 Ki = 451 nM, Kb = 460 nM) with additional inhibitory activity against PDE4B PDE7A (PDE4B IC50 = 80.4 μM; PDE7A IC50 = 151.3 μM). Its antidepressant-like effect surpasses that of the reference agent, escitalopram.

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.

Compound 22, a 5-hydroxynitrile rubber 7 receptor antagonist (5-HT1A Ki=8 nm, Kb=0.04 nm; 5-nitrile rubber 7K I=451 nm, Kb=460 nm), exhibits inhibitory activity against PDE4B PDE7A (PDE4B IC50=80.4 μM; PDE7A IC50=151.3 μM). It demonstrates significant passive biofilm penetration capabilities and high metabolic stability in vitro. Pharmacological assessment has revealed precognitive and antidepressant effects in rat behavioral tests, highlighting its potential therapeutic applications.

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.

Difamilast is an inhibitor of phosphodiesterase IV.

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

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

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.

Mesembrine ((+)-Mesembrine), a primary alkaloid distinguished by its aryloctahydroindole structure, acts as a potent 5-HT transporter inhibitor with an inhibition constant (K i) of 1.4 nM. Additionally, it demonstrates inhibitory activity against phosphodiesterase 4B (PDE4B) with an inhibitory concentration 50% (IC50) of 7.8 μM [1] [2].

PDE4-IN-10 (compound 7a) is a potent PDE4 inhibitor with an IC50 of 7.01 μM for PDE4B, demonstrating selectivity, microsomal stability, TNF-α inhibition, and no major toxicities in vitro [1].

GSK256066 is a selective PDE4B(equal affinity to isoforms A-D) inhibitor with IC50 of 3.2 pM, >380, 000-fold selectivity versus PDE1 2 3 5 6 and >2500-fold selectivity against PDE4B versus PDE7.Phase 2.

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.

MDL3, a novel inhibitor of PDE4B and PDE5A, demonstrates resilience against liver damage and inflammation while inhibiting pathological remodeling of adipose tissue.

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.

P7-2302 inhibits PDE7 and PDE4B with IC50 values of 0.18 nM and 77.3 nM, respectively. It also inhibits the efflux of P-gp and BCRP (breast cancer resistance protein) and shows low uptake in rat brains. When labeled with 18F, P7-2302 can be used as a PET tracer.

Nerandomilast (BI 1015550) is an orally active PDE4B inhibitor with IC50 of 7.2 nM. BI 1015550 has potential applications in inflammation, allergic diseases, pulmonary fibrosis and chronic obstructive pulmonary disease (COPD) with a good safety profile.

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].

GSK 256066 Trifluoroacetate is a selective and high-affinity phosphodiesterase 4 (PDE) inhibitor (IC50: 3.2 pM for PDE4B). It can be used for the treatment of chronic obstructive pulmonary disease.