PDE

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.

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.

Luteolin (Luteolol) belongs to the flavonoid group of natural products and is a Nrf2 inhibitor, PDE inhibitor. Luteolin has a wide range of biological activities including antitumor, antioxidant, anti-inflammatory, antimicrobial, antiviral, antiallergic, and procoagulant.

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.

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.

MR-L2 is a reversible and noncompetitive allosteric activator of long-isoform phosphodiesterase-4 (PDE4).

PF-04822163 is a potent inhibitor of PDE1 with IC50 value of 0.0024 μM.

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).

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

Zaprinast is a cGMP-selective phosphodiesterase (PDE) inhibitor and a GPR35 agonist. It has a strong activating effect on rat GPR35 and a certain activating effect on human GPR35. It reduces vascular remodeling through anti-proliferative and pro-apoptotic effects.

TPN171 is potent PDE5 inhibitor with subnanomolar potency for PDE5 and good selectivity over PDE6, which has the potential for the treatment of pulmonary arterial hypertension (PAH). TPN171 was proven to exert a longer lasting effect than sildenafil in animal models, providing a foundation for a once-daily oral administration for its clinical use.

Isoprenaline hydrochloride (NCI-c55630) is a potent beta-adrenergic agonist with the peripheral vasodilator, bronchodilator, and cardiac stimulating properties.

Difamilast is an inhibitor of phosphodiesterase IV.

Roflumilast N-oxide is an inhibitor of PDE type 4.

Tanimilast (CHF-6001) is a novel, potent, and selective phosphodiesterase 4 inhibitor with an IC50 value of 0.026 ± 0.006 nM. It exhibits potent anti-inflammatory activity and is indicated for topical use in the lungs. Tanimilast was studied for its effects on obstructive lung disease.

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.

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.

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).

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.

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.

Cudetaxestat (BLD-0409) is a potent, orally active autotaxin inhibitor.

PF-04957325 is a potent and selective inhibitor of PDE8.PF-04957325 has an IC50 of 0.7 nM for PDE8A and 0.3 nM for PDE8B.PF-04957325 can be used to study autoimmune encephalomyelitis.

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.

Tadalafil (IC-351) is a carboline-based compound with vasodilatory activity that selectively inhibits the cyclic guanosine monophosphate (cGMP)-specific type 5 phosphodiesterase (PDE-5), preventing cGMP degradation in the smooth muscle of the corpus cavernosa and corpus spongiosum of the penis, thereby causing prolonged muscle relaxation, vasodilation, and enhanced penile erection.

Levosimendan (OR1259) is a calcium sensitizer used in the management of acutely decompensated congestive heart failure. It increases the sensitivity of the heart to calcium, thus increasing cardiac contractility without a rise in intracellular calcium. Levosimendan exerts its effect by increasing calcium sensitivity of myocytes by binding to cardiac troponin C in a calcium-dependent manner.

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

Naproxen is a COX-1 and COX-2 inhibitor (IC50s: 8.72 and 5.15 μM, respectively in cell assay). Naproxen etemesil is a lipophilic and non-acidic prodrug of naproxen. It is hydrolyzed to pharmacologically active Naproxen once absorbed.

Moracin M, a phenolic compound found in the skin of Morus alba Linn., effectively inhibits phosphodiesterase-4 (PDE4), exhibiting IC50 values of 2.9 μM and 4.5 μM for PDE4D2 and PDE4B2, respectively, and showing significantly lesser activity on PDE5A1 and PDE9A2 with values over 40 μM and 100 μM, respectively. This compound demonstrates notable anti-inflammatory activity.

Drotaverine hydrochloride is a type 4 cyclic nucleotide phosphodiesterase (PDE4) inhibitor，and is an antispasmodic drug, used to enhance cervical dilation during childbirth. Drotaverine hydrochloride is structurally related to papaverine

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.

Indomethacin (Indomethacin) is a COX1 and COX2 inhibitor (IC50=18 26 nM) with blood-brain barrier permeability and non-selectivity. Indomethacin is a non-steroidal anti-inflammatory agent with anti-tumor and anti-infective activity.

Nortadalafil (Demethyl Tadalafil) is demethyl Tadalafil, which is a PDE5 inhibitor, treating erectile dysfunction (ED) ; and under the name Adcirca for the treatment of pulmonary arterial hypertensio.

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

Enpp-1-IN-14 is a potent inhibitor of Ectonucleotide Pyrophosphatase Phosphodiesterase-1 (ENPP1) with an IC50 value of 32.38 nM for recombinant human ENPP-1. Enpp-1-IN-14 has anti-tumor activity.

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

Dovramilast (CC-11050) is an orally active phosphodiesterase 4 (PDE4) inhibitor that reduces the production of pro-inflammatory mediators and cytokines. Dovramilast is used in the study of Mycobacterium tuberculosis infections and lupus erythematosus.

Fraxin (Fraxoside) is a glucoside of fraxetin.

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.

Sildenafil citrate (UK-92480 citrate) , a cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase type 5 (PDE5) Inhibitor, is used extensively for erectile dysfunction and less commonly for pulmonary hypertension.

Theobromine (3,7-Dimethylxanthine), a xanthine alkaloid, is used as a bronchodilator and as a vasodilator.

TP-10 is a selective inhibitor of PDE10A against other PDEs with IC50 of 0.8 nM.

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.

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.

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.

Carbazeran (UK-31,557) is an inhibitor of PDE2 and PDE3 and can be used for studies about metabolic diseases. Carbazeran shows inotropic and chronotropic effects in vivo(EC50 = 100 μM).

Triflusal (UR1501) is a 2-acetoxy-4-trifluoromethylbenzoic acid and it is an aspirin chemically-related molecule but not a derivative.

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.

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.

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

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