phosphodiesterase

Phosphodiesterase (PDE), an enzyme capable of catalyzing the hydrolysis of the 3' ring phosphate bond in cyclic nucleotides, plays a crucial role in biochemical research and acts as a vital regulator in signal transduction processes involving the second messenger molecules cAMP and cGMP. Distinguished by their specificity to cyclic nucleotides, PDEs are categorized into different types ranging from PDE1 to PDE11, presenting potential significance in the study and treatment of various diseases [1].

IBMX (Methylisobutylxanthine) is a broad-spectrum phosphodiesterase (PDE) inhibitor with inhibitory activity against PDE3, PDE4, and PDE5 (IC50=6.5 26.3 31.7 μM). IBMX enhances the intracellular cAMP level.

Bucladesine sodium (DC2797) is a cAMP analog with cell-permeable properties. Bucladesine sodium is also a cAMP-dependent protein kinase (PKA) activator and a phosphodiester (PDE) inhibitor. Bucladesine sodium has anti-inflammatory activity.

Theophylline (1,3-Dimethylxanthine) is a methyl xanthine derivative from tea with diuretic, smooth muscle relaxant, bronchial dilation, cardiac, and central nervous system stimulant activities. It inhibits the 3', 5'-cyclic nucleotide phosphodiesterase that degrades cyclic AMP, thus potentiating the actions of agents that act through adenylyl cyclases and cyclic AMP.

Vesnarinone (Arkin) (INN) is a mixed phosphodiesterase 3 inhibitor and ion-channel modifier that has modest, dose-dependent, positive inotropic activity, but minimal negative chronotropic activity. It also suppresses cell proliferation and induces apoptosis by inducing the expression of p21, an inhibitor of cyclin-dependent kinase activity in p53-mediated cell cycle arrest.

Pentoxifylline (PTX) modulates immunologic activity by stimulating cytokine production. Pentoxifylline is a methylxanthine derivative that inhibits phosphodiesterase and affects blood rheology. It also inhibits platelet aggregation and improves blood flow by increasing erythrocyte and leukocyte flexibility.

Vardenafil (Vivanza) is an oral therapy for the treatment of erectile dysfunction. It is a selective inhibitor of cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase type 5 (PDE5). Penile erection is a hemodynamic process initiated by the relaxation of smooth muscle in the corpus cavernosum and its associated arterioles. During sexual stimulation, nitric oxide is released from nerve endings and endothelial cells in the corpus cavernosum. Nitric oxide activates the enzyme guanylate cyclase resulting in increased synthesis of cyclic guanosine monophosphate (cGMP) in the smooth muscle cells of the corpus cavernosum. The cGMP in turn triggers smooth muscle relaxation, allowing increased blood flow into the penis, resulting in erection. The tissue concentration of cGMP is regulated by both the rates of synthesis and degradation via phosphodiesterases (PDEs). The most abundant PDE in the human corpus cavernosum is the cGMPspecific phosphodiesterase type 5 (PDE5); therefore, the inhibition of PDE5 enhances erectile function by increasing the amount of cGMP.

Vinpocetine (RGH-4405) is a selective inhibitor of cyclic GMP phosphodiesterase (PDE).

Doxofylline (Doxophylline) is a methylxanthine derivative with the presence of a dioxolane group in position 7. As a drug used in the treatment of asthma, doxofylline has shown similar efficacy to theophylline but with significantly fewer side effects in animal and human studies.

Milrinone (Win 47203) is a Phosphodiesterase 3 Inhibitor. The mechanism of action of milrinone is as a Phosphodiesterase 3 Inhibitor.

N-Methylbenzamide is a potent inhibitor of phosphodiesterase 10A (PDE10A) with demonstrated anti-cancer activity.

Amrinone (Inocor) is a positive inotropic cardiotonic (cardiotonic agent) with vasodilator properties, phosphodiesterase 3 inhibitory activity.

Dipyridamole (Persantin) is a Platelet Aggregation Inhibitor. The physiologic effect of dipyridamole is by means of Decreased Platelet Aggregation.

Ibudilast (MN-166)(KC-404;AV-411;MN-166) is a relatively nonselective phosphodiesterase inhibitor. It is approved for use as an anti-inflammatory in Japan.

Acefylline (Theophylline-7-acetic acid), a stimulant drug of the xanthine chemical class, acts as an adenosine receptor antagonist. It is combined with diphenhydramine in the pharmaceutical preparation Etanautine to help offset its stimulant effects

Avanafil (TA1790) is a selective inhibitor of phosphodiesterase type 5 (PDE5) and is used as therapy of erectile dysfunction.

Icariin (Ieariline) belongs to the flavonol glycoside group of natural products, can inhibit PDE5 and PDE4 activity (IC50=432 73.50 μM), is also a PPARα activator. Icariin can increase cardiovascular and cerebrovascular blood flow, promote hematopoiesis, immunity and bone metabolism.

Crisaborole (AN-2728) is a phosphodiesterase 4 inhibitor.

Vardenafil hydrochloride is a New Phosphodiesterase Type 5(PDE5) Inhibitor, in the Treatment of Erectile Dysfunction in Men With Diabetes

Ziritaxestat (GLPG1690), an autotaxin inhibitor, currently being evaluated in an exploratory phase 2 study in idiopathic pulmonary fibrosis patients.

Butein is a cAMP-specific PDE inhibitor, protein tyrosine kinase inhibitor, and SIRT1 activator. It sensitizes HeLa cells to Cisplatin by targeting FoxO3a via the AKT and ERK p38 MAPK pathways.

ITI-214 is a picomolar PDE1 inhibitor with excellent selectivity against other PDE family members and against a panel of enzymes, receptors, transporters, and ion channels, exhibits potent PDE1 inhibitory activity (Ki = 58 pM).

Udenafil is an inhibitor of PDE5 .

Balipodect (TAK063) is a highly effective and selective PDE10A inhibitor (IC50: 0.30 nM); Its selectivity is >15000-fold over other PDEs.