Phosphodiesterase (PDE) Inhibitor

IBMX is a broad-spectrum phosphodiesterase (PDE) inhibitor, with IC₅₀s of 6.5, 26.3 and 31.7 μM for PDE3, PDE4 and PDE5, respectively.

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

Rolipram is a PDE4 inhibitor, with blood-brain barrier permeability, that reverses β-amyloid-induced learning and memory impairment in rats. Rolipram elevates intracellular cAMP and clevels and regulates the cAMP/CREB signaling pathway, thereby alleviating neuroinflammation and apoptotic responses. Rolipram promotes neuronal differentiation of human bone marrow mesenchymal stem cells and inhibits Methamphetamine- and morphine-induced hyperlocomotion in mice. Rolipram also reduces the viability of glioblastoma stem-like cells and enhances Bevacizumab (HY-P9906)-induced cell death. Rolipram inhibits the expression of proinflammatory cytokines and enhances central noradrenergic transmission. Rolipram is mainly used in studies related to various central nervous system diseases including Alzheimer's disease, major depressive disorder, glioblastoma multiforme, and multiple sclerosis.

Roflumilast (APTA-2217) is a selective PDE4 inhibitor with IC₅₀s of 0.7, 0.9, 0.7, and 0.2 nM for PDE4A1, PDE4A4, PDE4B1, and PDE4B2, respectively, without affecting PDE1, PDE2, PDE3 or PDE5 isoenzymes from various cells.

Sildenafil (UK-92480) is a potent phosphodiesterase type 5 (PDE5) inhibitor with an IC₅₀ of 5.22 nM.

Avanafil (TA-1790) is a potent and selective phosphodiesterase-5 (PDE-5) inhibitor with IC₅₀ values of 5.2 nM, 630 nM, 5700 nM, 6200 nM, 12000 nM, 27000 nM, 51000 nM and 53000 nM for PDE-5, PDE-6, PDE-4, PDE-10, PDE-8, PDE-7, PDE-2 and PDE-1, respectively. Avanafil activates NO/cGMP/PKG signaling-pathway to decrease loss in BMD, bone atrophy, and oxidative stress. Avanafil inhibits cyclic guanosine monophosphate (cGMP) hydrolysis and thus increases cGMP levels. Avanafil can be used for the research of erectile dysfunction and osteoporosis.

Icariin is a flavonol glycoside. Icariin inhibits PDE5 and PDE4 activities with IC₅₀s of 432 nM and 73.50 μM, respectively. Icariin also is a PPARα activator.

Theophylline (1,3-Dimethylxanthine) is a potent phosphodiesterase (PDE) inhibitor, adenosine receptor antagonist, and histone deacetylase (HDAC) activator. Theophylline (1,3-Dimethylxanthine) inhibits PDE3 activity to relax airway smooth muscle. Theophylline (1,3-Dimethylxanthine) has anti-inflammatory activity by increase IL-10 and inhibit NF-κB into the nucleus. Theophylline (1,3-Dimethylxanthine) induces apoptosis. Theophylline (1,3-Dimethylxanthine) can be used for asthma and chronic obstructive pulmonary disease (COPD) research.

Ro 20-1724 (Ro 20-174) is a potent inhibitor of cAMP-specific phosphodiesterase (PDE4/PDE IV) with a K_i of 1930 nM. Neuroprotective effect.

Dipyridamole is an orally active phosphodiesterase (PDE) inhibitor. Dipyridamole also is an antiplatelet agent used in secondary prophylaxis against stroke. Dipyridamole can induce cancer cell-specific apoptosis.

Milrinone is a PDE3 inhibitor, and also an inotrope and vasodilator.

Apremilast (CC-10004) is an orally available inhibitor of type-4 cyclic nucleotide phosphodiesterase (PDE-4) with an IC₅₀ of 74 nM. Apremilast inhibits TNF-α release by lipopolysaccharide (LPS) with an IC₅₀ of 104 nM.

W-7 hydrochloride is a selective calmodulin antagonist. W-7 hydrochloride inhibits the Ca²⁺-calmodulin-dependent phosphodiesterase and myosin light chain kinase with IC₅₀ values of 28 μM and 51 μM, respectively. W-7 hydrochloride induces apoptosis and has antitumor and vascular relaxing activity. W-7 hydrochloride is a blocker of Kv4.3 and can be used for research of arrhythmias.

Tadalafil (IC-351) is a PDE5 inhibitor with an IC₅₀ value of 1.8 nM.

Cilostazol (OPC 13013) is a potent and selective inhibitor of phosphodiesterase (PDE) 3A, the isoform of PDE 3 in the cardiovascular system, with an IC₅₀ of 0.2 μM.

Sildenafil citrate is a potent phosphodiesterase type 5 (PDE5) inhibitor with IC₅₀ of 5.22 nM.

Cilostamide is a selective and potent PDE3 inhibitor, with IC₅₀s of 27 nM and 50 nM for PDE3A and PDE3B, respectively, and has antithrombotic and anti-intimal hyperplastic activity.

Pentoxifylline (BL-191), a haemorheological agent, is an orally active non-selective phosphodiesterase (PDE) inhibitor, with immune modulation, anti-inflammatory, hemorheological, anti-fibrinolytic and anti-proliferation effects. Pentoxifylline can be used for the research of peripheral vascular disease, cerebrovascular disease and a number of other conditions involving a defective regional microcirculation.

Crisaborole (AN-2728) is a potent inhibitor of PDE4 and cytokine release; inhibit PDE4 with an IC₅₀ of 0.49 μM.

ITI-214 is a potent, CNS-active, orally bioavailable PDE1 inhibitor (K_i of 58 pM) with excellent selectivity against other PDE family members and against a panel of enzymes, receptors, transporters and ion channels. ITI-214 inhibits recombinant full-length human PDE1A, PDE1B and PDE1C with K_is of 33 pM, 380 pM and 35 pM, respectively. ITI-214 shows efficacy in various animal models of motor and cognitive functions.