pde

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.

PDE-I2 is a parasite schizogony inhibitor.

PDE-9 inhibitor is used for treatment neurodegenerative diseases.

ethyl 1-(4-aminophenyl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxylate, also known as EAPT, is a potent and selective PDE4 inhibitor that regulates intracellular cyclic adenosine monophosphate (cAMP) levels. It has been used in a variety of scientific applications, including the study of cAMP-mediated signaling pathways, and has potential as a therapeutic agent for the treatment of inflammatory and immune-related diseases.

PDE9-IN-1 is a selective and orally bioavailable Inhibitor of PDE9A(IC50 of 8.7 nM).

K-Ras-PDEδ-IN-1 is a potent inhibitor of competitive K-Ras-PDEδ that binds to the farnesyl binding pocket of PDEδ (Kd of 8 nM).

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.

PDE4-IN-4 is a compound acting as both a potent M3 antagonist (p IC 50 = 10.2) and a PDE4 inhibitor (p IC 50 = 8.8), designed for inhalation-based treatment of pulmonary diseases.

PDE4-IN-3 is a newly developed oral compound that acts as a potent inhibitor of the enzyme phosphodiesterase 4 (PDE4), displaying a high affinity for inhibition with an IC50 value of 4.2 nM.

PDE12-IN-1 is a powerful and specific inhibitor of PDE12, exhibiting a pIC 50 value of 9.1 for enzyme inhibition. It effectively enhances levels of 2′,5′-linked adenylate polymers (2-5A), with a pEC 50 value of 7.7. Additionally, PDE12-IN-1 demonstrates antiviral activity.

PDE2A-IN-1 is a phosphodiesterase 2A (PDE2A) inhibitor with an IC50 value of 1.3 nM.

PDE10-IN-5, a phosphodiesterase 10 (PDE10) inhibitor, is utilized for studying certain central nervous system disorders.

PDE7-IN-3 (Example 2) serves as an inhibitor of phosphodiesterase PDE7 and exhibits potential analgesic properties. It is applicable in the research of various pain types including inflammatory, neuropathic, visceral, and nociceptive pain [1].

PDE5-IN-10 (compound 4b), a potent phosphodiesterase type 5 (PDE5) inhibitor, exhibits an effective half-maximal inhibitory concentration (IC50) of 20 nM, enhanced in vitro microsomal stability (t 1/2 = 44.6 min), and excellent efficacy in restoring long-term potentiation, making it suitable for Alzheimer’s disease (AD) research [1].

PDE4-IN-13 is a phosphodiesterase 4 (PDE4) inhibitor exhibiting anti-inflammatory and antioxidant activities, with an half maximal inhibitory concentration (IC50) value of 1.56 μM. It is used in the research of chronic obstructive pulmonary disease (COPD) [1].

PDE4-IN-9 (Compound 5j) is a potent PDE4 inhibitor with an IC50 value of 1.4 μM against PDE4 in vitro enzyme assays, which is lower than the 2.0 μM of parent rolipram, and demonstrates good in vivo activity in LPS-induced animal models of asthma COPD and sepsis [1].

PDE4-IN-8 (Example 5) is a potent Phosphodiesterase 4 (PDE4) inhibitor with an IC50 value of 0.93 nM for PDE4B2. However, it has minimal effects on IL13, IL4, and IFNy, with IC50 values of 4.04 nM, 36.33 nM, and 2394 nM, respectively [1].

PDE4-IN-10 (compound 7a) is a potent PDE4 inhibitor with an IC50 of 7.01 μM for PDE4B, demonstrating selectivity, microsomal stability, TNF-α inhibition, and no major toxicities in vitro [1].

PDE4-IN-14 (Compound 1) is a phosphodiesterase 4 (PDE4) inhibitor used in research on PDE4-related diseases, such as inflammatory and immune disorders, cancer, and metabolic diseases [1].

PDE5-IN-11 is a potent PDE5 inhibitor with an IC50 of 40 nM and displays inhibitory activity against PDE4 and PDE6 with IC50 values of 1.78 μM and 0.09 μM, respectively [1].

PDE4B-IN-3 is a potent PDE4B inhibitor (IC50: 0.94 μM) with anti-inflammatory effects.

PDE7-IN-2 is an inhibitor of phosphodiesterase 7 (IC50 = 2.1 µM) and can be used in Parkinson's disease studies.

PDE4-IN-6 is a safe, potent and moderately selective inhibitor of PDE4, acting on PDE4B (IC50: 0.125 μM) and PDE4D (IC50: 0.43 μM). PDE4-IN-6 is able to down-regulate TNF-α and IL-6 expression levels, exhibits anti-inflammatory and anti-arthritic effects, and has potent immunomodulatory activity. PDE4-IN-6 has potential for anti-rheumatoid arthritis studies.

PDE5/HDAC-IN-1 is a potent inhibitor of phosphodiesterase 5 (PDE5) and HDAC, with IC50 values of 46.3 nM and 14.5 nM, respectively.

Compound 22, a 5-hydroxynitrile rubber 7 receptor antagonist (5-HT1A Ki=8 nm, Kb=0.04 nm; 5-nitrile rubber 7K I=451 nm, Kb=460 nm), exhibits inhibitory activity against PDE4B/PDE7A (PDE4B IC50=80.4 μM; PDE7A IC50=151.3 μM). It demonstrates significant passive biofilm penetration capabilities and high metabolic stability in vitro. Pharmacological assessment has revealed precognitive and antidepressant effects in rat behavioral tests, highlighting its potential therapeutic applications.

PDE1-IN-4 is a potent and selective inhibitor of PDE1 (phosphodiesterase-1), acting on PDE1C (IC50: 10 nM), PDE1A (IC50: 145 nM) and PDE1B (IC50: 354 nM). PDE1-IN-4 regulates cAMP (3′,5′-cyclic adenosine monophosphate) and cGMP (3′,5′-cyclic guanosine monophosphate) and exhibits antifibrotic effects. PDE1-IN-4 can inhibit TGF-β1-induced differentiation of human lung fibroblasts, and can be used to study idiopathic pulmonary fibrosis (IPF).

PDE5-IN-4, a phosphodiesterase 5 (PDE5) inhibitor, is utilized in research concerning acute myocardial infarction and reperfusion-related damage, gastrointestinal diseases, diabetic complications, and liver failure.

PDE4-IN-11 is a potent phosphodiesterase isoenzyme 4 (PDE4) inhibitor, exhibiting remarkable bronchodilatory and anti-inflammatory characteristics. It is specifically designed for studying obstructive or inflammatory airway diseases [1] [2] [3].

PDE11-IN-1 is a PDE11 inhibitor used for adrenal insufficiency research [1].

PDE1-IN-5 (Compound 10c) is a selective PDE1C inhibitor with an IC50 of 15 nM, exhibiting anti-inflammatory properties through the inhibition of iNOS, TNF-α, IL-1α, IL-1β, and IL-6 expression induced by LPS. It has demonstrated efficacy in mitigating inflammatory bowel disease (IBD) symptoms in a dextran sodium sulfate (DSS)-induced colitis mouse model, suggesting its potential utility for IBD research [1].

PDE11A4-IN-1 (compound 23b) is a potent, selective inhibitor of PDE11A4 with an IC50 of 12 nM, demonstrating high selectivity against PDE1, PDE2, PDE7, PDE8, and PDE9 [1].

PDE5-IN-5 is a selective inhibitor of phosphodiesterase 5 (PDE5) (IC50: 2.0 nM).

This compound is a dual 5-HT1A/5-HT7 receptor antagonist (5-HT1A Ki = 8 nM, Kb = 0.04 nM; 5-HT7 Ki = 451 nM, Kb = 460 nM) with additional inhibitory activity against PDE4B/PDE7A (PDE4B IC50 = 80.4 μM; PDE7A IC50 = 151.3 μM). Its antidepressant-like effect surpasses that of the reference agent, escitalopram.

PDE1-IN-1can enhance levels of the second messengers cAMP/cGMP leading to the expression of neuronal plasticity-related genes, neurotrophic factors, and neuroprotective molecules. These neuronal plasticity enhancement properties make PDE1 inhibitors good candidates as therapeutic agents in many neurological conditions.

PDE5-IN-9 inhibits Phosphodiesterase PDE1c and is used to treat hypertension, heart failure, myocardial infarction, kidney failure, asthma, bronchitis, and dementia.

PDE5-IN-3 (compound 11j) is a potent inhibitor of PDE5 (IC50: 1.57 nM) and has a moderate inhibitory effect on EGFR (IC50: 5.827 μM). It markedly inhibits the Wnt β-catenin pathway (IC50: 1286.96 ng mL), induces the intrinsic apoptotic mitochondrial pathway in HepG2 cells, and exhibits significant antitumor effects.

AChE PDE4-IN-1 (compound 12c) is a highly effective and specific dual inhibitor of PDE4 and AChE, with IC50 values of 0.28 μM for AChE and 1.88 μM for PDE4D. This compound shows notable potential in reducing neuroinflammation associated with Alzheimer's disease research [1].

PDE4-IN-5 (compound 33a) is a highly potent and selective PDE4 inhibitor with an IC50 value of 3.1 nM, exhibiting excellent skin permeability and a well-characterized binding mechanism. It also shows a notable anti-psoriasis effect [1].

PDE4-IN-12 is a potent and safe ubiquitous PDE4 inhibitor with an IC50 of 3.5 nM (SI: 2.71) and also acts on PDE7 with an IC50 of 15 nM (SI: 4.27).

M3/PDE4 Modulator-1 (compound 10f) serves as a bifunctional entity functioning both as an M3 mAChR antagonist and a PDE4 inhibitor. When administered intravenously at concentrations ranging from 10 to 1000 nM/kg, this compound effectively diminishes eosinophil influx into cysts within the OVA rat model [1].

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.

Lanopepden (GSK 1322322) is a potent peptide deformylase inhibitor effective against Staphylococcus aureus strains ATCC 29213 and ATCC 25923, and is applicable in the study of pneumonia, dermatological, and infectious diseases.

Lanopepden mesylate is a peptide deformylase inhibitor against Staphylococcus aureus.

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.

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.

Diphylline (Diprophylline) is a xanthine derivative. Diphylline exerts bronchodilator effects and to a lesser extent vasodilator and diuretic properties. Diphylline probably acts as a competitive inhibitor of phosphodiesterase which leads to an increase in intracellular cAMP. This results in relaxation of bronchial smooth muscle and other smooth muscles. Diphylline may also antagonize adenosinereceptors. Diphylline is used in the treatment of acute bronchial asthma, chronic bronchitis and emphysema.