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.

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.

Difamilast is an inhibitor of phosphodiesterase IV.

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.

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

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 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-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.

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.

PDE4B-IN-4 is an inhibitor of PDE4B (IC50: 2.82 nM) and TNF-α (IC50: 7.20 nM). It demonstrates anti-inflammatory properties by reducing neutrophilia in a mouse model of lipopolysaccharide (LPS)-induced sepsis.

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

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-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.

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.

PF-07038124 HCl is a selective and potent PDE4 inhibitor with an IC50 of 0.5 nM for PDE4B2.PF-07038124 HCl inhibits IL-13, IL-4, and IFNγ, and can be used in the study of skin disorders such as atopic dermatitis and plaque psoriasis.

Roflumilast (APTA 2217) is an orally available, long-acting inhibitor of phosphodiesterase (PDE) type 4 (PDE4), with anti-inflammatory and potential antineoplastic activities. Upon administration, roflumilast and its active metabolite roflumilast N-oxide selectively and competitively bind to and inhibit PDE4, which leads to an increase of both intracellular levels of cyclic-3', 5'-adenosine monophosphate (cAMP) and cAMP-mediated signaling.

FCPR03 is a selective inhibitor of phosphodiesterase 4 (PDE4) with IC50s of 31 nM, 47 nM, and 60 nM for PDE4B1, PDE4D7, and PDE4 catalytic domain, respectively. FCPR03 has neuroprotective, anti-inflammatory, and antidepressant-like effects.

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.

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.

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].

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].

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.

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].