pde1

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

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.

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.

Vardenafil hydrochloride trihydrate (BAY38-9456) is a new type PDE inhibitor with IC50 of 0.7 and 180 nM for PDE5 and PDE1, respectively.

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).

Vardenafil dihydrochloride (Levitra) is a new type PDE inhibitor with IC50 of 0.7 and 180 nM for PDE5 and PDE1, respectively.

PDE1-IN-2 is an PDE1 inhibitor(PDE1C, PDE1B and PDE1A with IC50 values of 6, 140 and 164 nM, respectvely).

PDE1-IN-3 is a selective inhibitor of human phosphodiesterase 1 (PDE1).

PDE1-IN-9 (Compound 7a) is a selective inhibitor of phosphodiesterase 1 (PDE1), targeting PDE1C with an IC50 value of 11 nM. It effectively reduces the mRNA expression of IL-1β, IL-6, TNF-α, and iNOS, while also inhibiting the production of nitric oxide (NO) and reactive oxygen species (ROS). Additionally, PDE1-IN-9 demonstrates good metabolic stability in rat liver microsomes.

PDE1-IN-8 (Compound 3f) acts as an inhibitor of PDE1, with an IC50 of 11 nM. It hinders cAMP and cGMP signaling pathways, impeding the differentiation and proliferation of cells into myofibroblasts, and demonstrates antifibrotic effects in the Bleomycin-induced rat model of pulmonary fibrosis.

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).

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.

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].

PDE1-IN-6 (compound 6c) functions as a highly selective PDE1 inhibitor, exhibiting an IC 50 value of 7.5 nM. It notably inhibits proliferation and induces apoptosis in acute myelogenous leukemia cells [1].

PDE1-IN-7 (Compound 13h), with an IC50 value of 10 nM, selectively inhibits bPDE1. This compound demonstrates significant anti-fibrotic effects in a BDL-induced liver fibrosis rat model and is useful for research purposes in studying liver fibrosis [1].

PDE10-IN-1 (SEP-0372814) is used for treating CNS and metabolic disorders.

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].

PDE12-IN-3 is an inhibitor of phosphodiesterase 12 (PDE12) (pXC50 of 7.68),with antiviral activity.

PDE2 PDE10-IN-1 is an inhibitor of phosphodiesterase 2 (PDE2) and PDE10, with IC50 values of 29 nM and 480 nM, respectively.

PDE11A4-IN-2 (compound 4g) is an orally bioavailable, brain-penetrant, selective, and potent inhibitor of PDE11A4.

PDE10A-IN-8 is a potent inhibitor of PDE10A.

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.

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

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