Cilostazol(OPC 13013; OPC 21) is a potent inhibitor of PDE3A, the isoform of PDE 3 in the cardiovascular system (IC50=0.2 uM).IC50 Value: 0.2 uM [1]Target: PDE3Ain vitro: Cilostazol caused a concentration-dependent increase in the cAMP level in rabbit and human platelets with similar potency. Furthermore, cilostazol and milrinone were equally effective in inhibiting human platelet aggregation with a median inhibitory concentration (IC50) of 0.9 and 2 microM, respectively. In rabbit ventricular myocytes, however, cilostazol elevated cAMP levels to a significantly lesser extent (p < 0.05 vs. milrinone) [2]. Cilostazol inhibited SIPA dose-dependently in vitro. The IC50 value of cilostazol for inhibition of SIPA was 15 +/- 2.6 microM (m +/- SE, n=5), which was very similar to that (12.5 +/- 2.1 microM) for inhibition of ADP-induced platelet aggregation. Cilostazolpotentiates the inhibition of SIPA by PGE1 and enhances its ability to increase cAMP concentrations [3].in vivo: A single oral adminstration of 100 mgcilostazol to healthy volunteers produced a significant inhibition of SIPA [3]. Male C57BL/6J mice were assigned to five groups: mice fed a normal diet (groups 1 and 2); 0.1% or 0.3% cilostazol-containing diet (groups 3 and 4, respectively); and 0.125% clopidogrel-containing diet (group 5). Two weeks after feeding, groups 2-5 were intraperitoneally administered carbon tetrachloride (CCl4 ) twice a week for 6 weeks, while group 1 was treated with the vehicle alone [4].Toxicity: Cilostazol in addition to dual antiplatelet therapy appears to be effective in reducing the risk of restenosis and repeat revascularization after PCI without any significant benefits for mortality or stent thrombosis [5].
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.IC50 value: 3.2 pM [1]Target: PDE4Bin vitro: GSK256066 is a slow and tight binding inhibitor of PDE4B with apparent IC50 of 3.2 pM. GSK256066 is an extremely potent inhibitor of LPS-stimulated TNFα production in PBMCs with pIC50 of 11.0 and IC50 of 10 pM and human whole-blood cultures with pIC50 of 9.90 and IC50 of 126 pM. GSK256066 is highly selective for PDE4 (>3.8 × 105-fold versus PDE1, PDE2, PDE3, PDE5, and PDE6 and >2.5 × 103-fold against PDE7). GSK256066 inhibits PDE4 isoforms A-D with equal affinity [1].in vivo: GSK256066 inhibits the LPS-induced pulmonary neutrophilia with an ED50 of 1.1 μg/kg, achieving maximal inhibition of 72% at 30 μg/kg when given in the aqueous suspension. GSK256066 inhibits the LPS-induced pulmonary neutrophilia with ED50 of 2.9 μg/kg, achieving maximal inhibition of 62% when given in the dry powder formulation. GSK256066 shows a moderate plasma clearance of 39 ml/min/kg, a moderate volume of distribution of 0.8 L/kg, and a relatively short half-life of 1.1 hour in the male CD rat [1]. GSK256066 sustains at a high lung concentration of 2.6 μg/g after intra-tracheal administration as an aqueous suspension at a dose of 30 μg/kg in rats [2]. GSK256066 (10 μg/kg) is administered intratracheally at different times (2, 6, 12, 18, 24, and 36 hours) before LPS administration, inhibiting LPS-Induced Pulmonary Neutrophilia in rat lipopolysaccharide (LPS)-induced models of acute pulmonary inflammation. GSK256066 (0.3–100 μg/kg) inhibits LPS-induced increases in exhaled nitric oxide with ED50 of 35 μg/kg in rat. GSK256066 (10 μg/kg) is administered half a hour before OVA administration in rat, inhibiting OVA-induced pulmonary eosinophilia with ED50 of 0.4 μg/kg. GSK256066 administered intratracheally as a dry powder blended in respiratory-grade lactose at doses of 3 to 100 μg/kg 2 hours before inhaled LPS challenge in ferrets, inhibiting LPS-induced pulmonary neutrophilia with ED50 of 18 μg/kg without inducing emetic episodes [3].
PDE5-IN-9 (Compound 59) is a PDE5 inhibitor (IC50: 11.2 μM). PDE5-IN-9 shows interaction with Gln 817, Tyr 612, and Ala 767 amino acid residues. PDE5-IN-9 can be used for research of cardiovascular disease[1].
MK-0952 is a selective and orally active PDE4 inhibitor, with an IC50 of 0.53 nM. MK-0952 has the potential for Alzheimer’s disease study[1][2].
FR-229934 is a PDE V inhibitor extracted from patent WO2019130052A1. FR-229934 can be used for the research of pulmonary arterial hypertension and erectile dysfunction[1].
Norbraylin, a natural prenylated coumarin, is a PDE4D2 inhibitor with an IC50 value of 7.15 μM[1].
Isopedicin potently and concentration-dependently inhibits superoxide anion (O2 U?) production in formyl-L-methionyl-L-leucyl-L-phenylalanine (FMLP)-activated cells. Isopedicin increases cAMP formation and PKA activity in FMLP-activated cells by inhibiting phosphodiesterase (PDE) activity[1].
PF-05180999 is a phosphodiesterase 2A (PDE2A) inhibitor, with an IC50 of 1.6 nM.
Mirodenafil-d7 (SK-3530-d7) dihydrochloride is the deuterium labeled Mirodenafil dihydrochloride. Mirodenafil dihydrochloride (SK3530 dihydrochloride) is a phosphodiesterase type 5 (PDE-5) inhibitor developed for the treatment of erectile dysfunction[1][2].
Win-62005 is a cyclic AMP phosphodiesterase III (PDE III) inhibitor with Kis of 25 and 26 nM for rat heart and canine aorta, respectively.
Amrinone (Inamrinone) is a positive inotropic-vasodilator agent. Amrinone is a selective phosphodiesterase III inhibitor that increases cyclic adenosine monophosphate by preventing its breakdown. Amrinone is also an orally active, non-glycosidic and non-catecholamine cardiotonic agent[1][2][3].
PDE4-IN-14 (Compound 1) is a PDE4 inhibitor that can be used in the study of PDE4-related diseases (such as inflammatory and immune diseases, cancer, and metabolic diseases, etc.)[1].
PAT-048 is a potent, selective and orally active autotaxin inhibitor, inhibits IL-6 mRNA expression, but shows no effect on autotaxin protein and pulmonary lysophosphatidic acid (LPA) production in lung fibrosis model. PAT-048 shows an IC50 and IC90 of 20 nM and 200 nM for autotaxin in mouse plasma. PAT-048 reduces dermal fibrosis in vivo[1][2].
PAT-347 is an Autotaxin (ATX) inhibitor. ATX is a secretory enzyme that hydrolyzes lysophosphatidylcholine (LPC) and regulates lysophosphatidic acid (LPA) production in the blood[1][2].
(R)-(-)-Rolipram is the R-enantiomer of Rolipram. Rolipram is a selective inhibitor of phosphodiesterases PDE4 with IC50 of 3 nM, 130 nM and 240 nM for PDE4A, PDE4B, and PDE4D, respectively.
Sildenafil Mesylate is an orally active and selective phosphodiesterase type 5 (PDE5) inhibitor. Sildenafil Mesylate can be used in studies of erectile dysfunction and cancer[1].
Deltarasin hydrochloride is an inhibitor of KRAS-PDEδinteraction with Kd of 38 nM for binding to purified PDEδ.
(S)-(+)-Rolipram is a PDE4-inhibitor and an anti-inflammatory agent, less potent than its R enantiomer.Target: PDE4B; PDE4DRolipram, a selective inhibitor of the cyclic AMP-specific phosphodiesterase (PDE IV). Rolipram did not inhibit 5-lipoxygenase activity but did inhibit human monocyte production of leukotriene B4 (LTB4, IC50 3.5 microM). Rolipram inhibited arachidonic acid-induced inflammation in the mouse, while the low Km-cyclic-GMP PDE inhibitor. Rolipram had a modest effect on LTB4 production in the mouse, but markedly reduced LTB4-induced PMN infiltration [1]. In humans and animals rolipram produces thereby a variety of biological effects. These effects include attenuation of endogenous depression and inflammation in the central nervous system (CNS), both effects are of potential clinical relevance [2].
PDE5-IN-5 (Compound 11) is a potent, selective phosphodiesterase 5 (PDE5) inhibitor with an IC50 of 2.0 nM[1].
PDE5-IN-42 (Compound 42) is a potent and orally active PDE5 inhibitor with an IC50 of 0.04 nM. PDE5-IN-42 maintains selectivity over PDE6 and PDE11[1].
Tanimilast (CHF-6001) is a novel highly potent and selective phosphodiesterase 4 inhibitor(IC50=0.026 ± 0.006 nM) with robust anti-inflammatory activity and suitable for topical pulmonary administration.Tanimilast is used for the research of obstructive lung diseases[1].
Nauclefine is an indole alkaloid isolated from Nauclea officinalis. Nauclefine acts as a PDE3A modulator to induce cancer cell apoptosis through a PDE3A-SLFN12-dependent death pathway[1].
Senazodan is a Ca2+ sensitiser, and also shows inhibition effect on PDE III.
Dyphylline acts as an adenosine receptor antagonist and phosphodiesterase inhibitor, which is used in the treatment of respiratory disorders.Target: Adenosine Receptor; PDEDyphylline (trade names Dilor, Lufyllin), also known as diprophylline, is a xanthine derivative with bronchodilator and vasodilator effects. It is used in the treatment of respiratory disorders like asthma, cardiac dyspnea, and bronchitis. It acts as an adenosine receptor antagonist and phosphodiesterase inhibitor.
Bay 60-7550 is a potent and selective PDE2 inhibitor with a Ki of 3.8 nM.
A novel small molecule inhibitor of PDE6δ/KRas interaction with Kd of 203 pM; inhibits PDE6δ/KRas interaction in cells with Kd of 85 nM, selectively inhibits growth of KRas mutated and -dependent cells.
TPN729 is a novel potent, selective phosphodiesterase type 5 (PDE5) inhibitor with IC50 of 2.28 nM, shows better selectivity profile 2.5 times higher than sildenafil against PDE6 and 500 times higher than tadalafil against PDE11; selectively inhibits PDE5 and blocks the degradation of cyclic guanosine monophosphate, and is a promising PDE5 inhibitor providing fewer side effects and better compliance.
Deltasonamide 2 is a PDEδ inhibitor with a Kd of ~385 pM[1].
Enpp-1-IN-17 (example 274) is a potent ENPP1 inhibitor, with the inhibition constants (Ki values) toward cGAMP and ATP hydrolysis of 100 nM-1 μM and > 1 μM, respectively. The selectivity ratio for inhibition of cGAMP hydrolysis versus ATP hydrolysis is >6.4[1].
Anagrelide, an inhibitor of phosphodiesterase type III (PDEIII) (IC50=36 nM), inhibits platelet production. Anagrelide, an imidazoquinazoline derivative, acts as an inhibitor of platelet aggregation. Anagrelide plays in the antithrombopoietic action. The platelet-lowering agent[1].