Phosphodiesterase (PDE) Inhibitor

PDE5-IN-10 (compound 4b) is a potent PDE5 inhibitor with an IC₅₀ of 20 nM. PDE5-IN-10 improves in vitro microsomal stability (t_1/2 = 44.6 min) as well as excellent efficacy in restoring long-term potentiation. PDE5-IN-10 can be used for Alzheimer’s disease (AD) research.

Anagrelide-¹³C₂,¹⁵N,d₂ is ¹⁵N and deuterated labeled Anagrelide (HY-B0523). Anagrelide is a potent inhibitor of phosphodiesterase type III (PDE3) (IC₅₀=36 nM). Anagrelide, an imidazoquinazoline derivative, acts as an inhibitor of platelet aggregation. Anagrelide inhibits bone marrow megakaryocytopoiesis. Anagrelide decreases gastrointestinal stromal tumor (GIST) cell proliferation and promotes their apoptosis in vitro. Anagrelide is a platelet-lowering agent and plays in the antithrombopoietic action.

JNJ-42314415 is a centrally active phosphodiesterase 10A (PDE10A) inhibitor, with K_i values of 35 nM and 64 nM for human recombinant PDE10A and rPDE10A, respectively.

LH17, a Kaempferol (HY-14590) derivative, is a potent and selective PDE4 inhibitor (PDE4D2 IC₅₀ = 73 nM, PDE4B2 IC₅₀ = 190 nM). LH17 exhibits remarkable selectivity (>136-fold) against other PDE isoforms (PDE1B/2A/3A/5A/8A/9A/10A) (IC₅₀ > 10000 nM), with the exception of PDE7A1 (IC₅₀ = 300 nM). LH17 distinctly interacts with PDE4 M-pocket. LH17 demonstrates remarkable anti-fibrotic efficacy in both in vitro and in vivo models. LH17 can be used for idiopathic pulmonary fibrosis (IPF) research.

1,3,5-Trihydroxy-4-prenylxanthone is a Na⁺/H⁺ exchange system inhibitor with a minimum inhibitory concentration of 10 μg/mL. 1,3,5-Trihydroxy-4-prenylxanthone is a phosphodiesterase type 5 (PDE5) inhibitor with an IC₅₀ value of 3.0 μM. 1,3,5-Trihydroxy-4-prenylxanthone inhibits Lipopolysaccharide (LPS) (HY-D1056)-induced NO production in RAW264.7 macrophages, and has anti-inflammatory activities.

FR-181074 is a selective and orally active PDE V inhibitor. FR-181074 can specifically block PDE V to inhibit the degradation of cyclic guanosine monophosphate (cGMP) in order to relax smooth muscle. FR-181074 can be used for the researches of cardiovascular disease and endocrinology, such as hypertension and erectile dysfunction.

PDE4-IN-32 (Compound B05) is a selective, blood-brain barrier permeable PDE4B and PDE4D inhibitor with IC₅₀ values of 13.7 nM and 23.8 nM, respectively. PDE4-IN-32 promotes the recovery of motor and cognitive function in MCAO/R mouse models. PDE4-IN-32 reduces cerebral edema. PDE4-IN-32 can be used for the research of ischemic stroke.

NVP-ABE171 is an efficient, long-lasting and orally active PDE4 inhibitor with IC₅₀ values for PDE4D, PDE4B, PDE4A and PDE4C of 1.5, 34, 602 and 1230 nM respectively. NVP-ABE171 enhances the cAMP accumulation induced by isoproterenol, inhibits the oxidative burst of eosinophils and the release of inflammatory cytokines from T cells and monocytes. NVP-ABE171 exhibits potent anti-inflammatory activity in animal models of asthma and pulmonary inflammation. NVP-ABE171 can be used for research on asthma and chronic obstructive pulmonary disease.

PDE4B-IN-5 (compound 84) is a PDE4B inhibitor, with an IC₅₀ value <10 nM. PDE4B-IN-5 has anti-inflammatory activity.

PDE5/CA-IN-1 is a dual PDE5 and carbonic anhydrase (CA) inhibitor, with IC₅₀ values of 0.41, 38.4, and 9.1 nM against PDE5, hCA II, and hCA VA, respectively. PDE5/CA-IN-1 inhibits multiple hCA subtypes associated with Alzheimer's disease. As a cytoprotective agent and oxidative stress alleviator, PDE5/CA-IN-1 reduces oxidative stress, and prevents recognition memory and working memory impairments. PDE5/CA-IN-1 is available for the research of Alzheimer's disease.

PDE1-IN-12 (P78, the first compound in 12) is a PDE1 inhibitor. PDE1-IN-12 inhibits PDEl-mediated suppression of the dopamine D1 receptor intracellular pathway and can be used for narcolepsy.

PAT-078 is a type II autotaxin (ATX) inhibitor. PAT-078 mainly occupies the hydrophobic pocket of ATX, blocks the bottleneck region between the hydrophobic channel and the catalytic site, and does not interact with the zinc ion at the catalytic site.

ATI22-107 is a dual-pharmacophore compound designed to simultaneously inhibit cardiac phosphodiesterase (PDE-III) and L-type calcium channels (LTCC), with activity that has specific effects on calcium cycling and contractility in cat ventricular myocytes and trabeculae.

ATX inhibitor 26 is an Autotaxin (ATX) inhibitor with an IC₅₀ of 57 nM in human plasma. ATX inhibitor 26 inhibits cell migration and collagen gel contraction. ATX inhibitor 26 has significant anti-fibrotic effects, reducing collagen deposition in a Bleomycin (BLM) (HY-108345)-induced pulmonary fibrosis model.

12-epi-Tadalafil is a PDE5 inhibitor (IC₅₀: 0.09 μM). 12-epi-Tadalafil can be used for research of cardiovascular diseases.

THPP-2 is a tetrahydropyridopyrimidine-type phosphodiesterase 10A (PDE10A) inhibitor with a K_i of 94 nM. THPP-2 is applicable to the research of schizophrenia.

PDE1-IN-7 (Compound 13h) is a selective inhibitor of bPDE1 (IC₅₀= 10 nM). PDE1-IN-7 exhibits significant anti-fibrotic effects in a BDL-induced liver fibrosis rat model. PDE1-IN-7 can be used for research in liver fibrosis.

PDE5-IN-15 (compound 21) is a xanthine derivative and PDE5 inhibitor, with IC₅₀ values of 0.002, 0.180, 2.85 and 2.22 μM against hPDE5, bPDE6, bPDE1 and hPDE3, respectively. PDE5-IN-15 has good oral bioavailability in dogs. PDE5-IN-15 can be used in research on male erectile dysfunction.

NCI-14465 is an ectonucleotide pyrophosphatase/phosphodiesterase (ENPP1) inhibitor with an IC 50 of 26.4 μM. NCI-14465 can be used in cancer research.

Tibenelast (LY186655) free acid is a potent and orally active is a phosphodiesterase inhibitor. Tibenelast free acid is an anti-asthma agent Tibenelast free acid increases the heart rate response to isoproterenol (HY-108353). Tibenelast free acid shows anti-anaphylactic shock activity. Tibenelast free acid has the potential for the research of asthma and other respiratory diseases.