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].

Sphingomyelin phosphodiesterase, a hydrolase, plays a crucial role in sphingomyelin metabolism by catalyzing the conversion of sphingomyelin into phosphocholine and ceramide. Furthermore, it is instrumental in cellular differentiation, immune and inflammatory responses, as well as intracellular cholesterol trafficking and metabolism [1] [2].

Phosphodiesterase 2 (II), a key enzyme prominently involved in the hydrolysis of vital second messengers, cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP), is frequently utilized in biochemical research. This enzyme is expressed across various tissues including the adrenal medulla, brain, heart, platelets, macrophages, and endothelial cells, playing a significant role in the regulation of diverse intracellular processes [1].

Phosphodiesterase 4 (PDE4) inhibitor is an inhibitor of PDE4 with an IC50 value of 0.10 μM for the human recombinant enzyme.

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.

Butein (2’,3,4,4’-tetrahydroxy Chalcone), a plant polyphenol, is isolated from Rhus verniciflua. It can inhibit the activation of protein tyrosine kinase, NF-κB and STAT3, and also can inhibit EGFR.

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.

Apremilast (CC-10004) (CC-10004) is a potent and orally active PDE4 (IC50=74 nM) with anti-inflammation activities.

Theophylline monohydrate (Quibron) appears to inhibit phosphodiesterase and prostaglandin production, regulate calcium flux and intracellular calcium distribution, and antagonize adenosine. Theophylline monohydrate is a natural alkaloid derivative of xanthine isolated from the plants Camellia sinensis and Coffea arabica. Physiologically, this agent relaxes the bronchial smooth muscle, produces vasodilation (except in cerebral vessels), stimulates the CNS, stimulates the cardiac muscle, induces diuresis, and increases gastric acid secretion; it may also suppress inflammation and improve contractility of the diaphragm.

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.

Cilostazol (OPC 21) is a Phosphodiesterase 3 Inhibitor. The mechanism of action of cilostazol is as a Phosphodiesterase 3 Inhibitor.

Irsogladine (Dicloguamine) is an anti-gastric ulcer agent that facilitates gap-junctional intercellular communication through M1 muscarininc acetylcholine receptor binding.

Deltarasin is a small molecular inhibitor of KRAS-PDEδ interaction with Kd of 38 nM for binding to purified PDEδ.

Amlexanox (AA673) is an anti-aphthous ulcer drug. Amlexanox inhibits the synthesis and release of inflammatory mediators, including leukotrienes and histamine, from mast cells, neutrophils, and mononuclear cells. Amlexanox also acts as a leukotriene D4 antagonist and a phosphodiesterase inhibitor. Amlexanox decreases the time ulcers take to heal as well as the pain associated with the ulcers.

Icariin (Ieariline) is a flavonol glycoside, inhibiting PDE5 and PDE4 activities. Icariin also is a PPARα activator.

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.

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.

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

OPC18750 HCl is a potential phosphodiesterase inhibitor with positive inotropic effects that can be used to study asthma, cancer, diabetes, and psychiatric disorders.

RS-25344 is a potent and selective phosphodiesterase (PDE) 4 inhibitor. It inhibits eosinophil chemotaxis and increases progressive motility of spermatozoa in vitro.

Arofylline (LAS 31025) is a PDE4 inhibitor and can be used for asthma studies.

Gisadenafil (UK-369003) is a selective inhibitor of phosphodiesterase 5 (PDE5) with an IC50 of 3.6 nM and prevents degradation of cGMP.

Torbafylline, a xanthine derivative, is a phosphodiesterase (PDE) inhibitor that attenuates burn-induced protein hydrolysis in rat skeletal muscle through activation of the PDE4/cAMP/EPAC/PI3K/Akt pathway, and inhibits the enhanced ubiquitin-proteasome-dependent protein hydrolysis in skeletal muscle of cancer- and sepsis-prone rats.

Anagrelide (Xagrid) is a Platelet-reducing Agent. The mechanism of action of anagrelide is as a Phosphodiesterase 3 Inhibitor. The physiologic effect of anagrelide is by means of Decreased Platelet Production.

WAY-313170 Inhibits hedgehog signaling and phosphodiesterase.

Imazodan hydrochloride (CI-914 HCl) is a potent and selective type III phosphodiesterase inhibitor used in the treatment of chronic congestive heart failure.

Mopidamol (RA 233) is a phosphodiesterase inhibitor, a dipyridamole derivative, with anticancer activity that prevents retinal vascular defects in experimental diabetes.

5,7-Diacetoxy-8-methoxyflavone is derived from the roots of Scutellaria baicalensis and inhibits cAMP phosphodiesterase.

Filaminast (UNII-CDD69JC61J) is an analog of a phosphodiesterase 4 inhibitor (PDE4 inhibitor) and roliplam, which is used as an anti-asthma drug.

CP 461 (UNII-68OJX9I7DT), a specific PDE2A inhibitor, is a novel pro-apoptotic compound that inhibits cyclic GMP phosphodiesterase but not cyclooxygenase-1 or -2. CP 461 inhibits the growth of a variety of human tumor cell lines in vitro and selectively induces apoptosis in cancer cell lines, but not in normal cells.

PDE IV-IN-1 is a potent phosphodiesterase 4 (PDE4) inhibitor with anti-inflammatory activity for the treatment of asthma, chronic obstructive pulmonary disease and other inflammatory diseases, and is a potential compound for the study of depression.

PDE9-IN-(S)-C33 ((S)-C33) is a potent and selective inhibitor of PDE9 (IC50 = 11 nM). PDE9-IN-(S)-C33 can be used for central nervous system diseases and diabetes research.

PF-03049423 is a potent and highly selective phosphodiesterase-5A inhibitor with an IC50 of approximately 0.2 nM for rat and human thrombomodulin. PF-03049423 can be used in studies about acute ischemic stroke studies.

uk-50001 is a phosphodiesterase (PDE) 4 inhibitor that can be used for many diseases, especially inflammation, allergies, respiratory diseases, disorders and conditions and wounds.

GEBR-7b (3-(Cyclopentyloxy)-4-methoxybenzaldehyde) is a phosphodiesterase-4 (PDE4) inhibitor.

WAY127093B racemate is the racemate of WAY127093B. WAY127093B is a phosphodiesterase IV inhibitor with oral activity in rats and guinea pigs.

CALP2 acetate is an antagonist of calmodulin showing high affinity for binding to the CaM EF-hand/Ca2+-binding site with a Kd of 7.9 µM. CALP2 acetate potently inhibits of adhesion and degranulation. CALP2 acetate is also a strong activator of alveolar macrophages. CALP2 acetate inhibits CaM-dependent phosphodiesterase activity and increases intracellular Ca2+ concentrations.

Vesnarinone HCl (OPC-8212 HCl) is an orally active phosphodiesterase 3 (PDE3) inhibitor.Vesnarinone HCl modulates calcium and potassium ions, increasing calcium flux and decreasing potassium flux.Vesnarinone HCl is a new positive inotropic compound that enhances myocardial contractility and can be be used in heart failure studies.

Parogrelil Free Base (NM-702 Free Base) is a selective phosphodiesterase 3 inhibitor with bronchodilatory and anti-inflammatory effects, inhibits leukotriene (LT)D(4) and histamine-induced constriction of isolated guinea pig tracheal strips, and can be used in the study of bronchial asthma.

Nanterinone (UK 61260), an orally available partial phosphodiesterase inhibitor, is a novel positive inotropic and balanced vasodilator compound.Nanterinone, when administered orally, results in significant improvements in acute haemodynamics, which may depend on pre-existing left ventricular filling pressures.Nanterinone is a novel positive inotropic and balanced vasodilator that has demonstrated acute hemodynamic effects in patients with mild to moderate heart failure.

Imazodan, a small molecule compound with positive inotropic activity, is a selective type III phosphodiesterase inhibitor and can be used to study heart failure.

UK 227786 is an inhibitor of phosphodiesterase 5 (PDE5), used for treatment of prostatic diseases.

CALP1 acetate is a calmodulin (CaM) agonist (Kd of 88 µM) that binds to the CaM EF-hand/Ca2+-binding site. CALP1 blocks calcium influx and apoptosis (IC50 of 44.78 µM) by inhibiting the open of calcium channel. CALP1 blocks glutamate receptor channels and blocks a store-operated nonselective cation channel. CALP1 activates CaM-dependent phosphodiesterase activity.

Isomazole is a novel orally available phosphodiesterase (PDE) inhibitor with calcium-sensitizing properties that inhibits PDE3 and PDE4.

Tanimilast (CHF-6001) is a novel, potent and selective phosphodiesterase 4 inhibitor with an IC 50 value of 0.026 ± 0.006 nM.Tanimilast has potent anti-inflammatory activity and is indicated for topical use in the lungs.Tanimilast was used in the study of obstructive lung disease.

Nauclefine (Parvine) is a plant indole alkaloid natural product and induces apoptosis of diverse cancer cells via a PDE3A-SLFN12 dependent death pathway. Nauclefine binds PDE3A but does not inhibit the PDE3A's phosphodiesterase activity.

T-0156 is a novel, potent and selective phosphodiesterase type 5 inhibitor that inhibits the hydrolysis of cyclic guanosine monophosphate (cGMP) with low affinity for PDE6, PDE1, PDE2, PDE3 and PDE4.

AWD 12-281 is a selective phosphodiesterase 4 (PDE4) inhibitor with anti-inflammatory and bronchodilator activity used in the study of chronic obstructive pulmonary disease (COPD).

5-Bromoimidazo[1,2-a]pyrazine inhibits phosphodiesterase and beta-adrenergic receptors.5-Bromoimidazo[1,2-a]pyrazine shows antibronchospastic activity in vitro.

MK-0873 is a novel and potent selective phosphodiesterase 4 (PDE4) inhibitor.