PDE1 Inhibitor

ITI-214 is a potent, CNS-active, orally bioavailable PDE1 inhibitor (K_i of 58 pM) with excellent selectivity against other PDE family members and against a panel of enzymes, receptors, transporters and ion channels. ITI-214 inhibits recombinant full-length human PDE1A, PDE1B and PDE1C with K_is of 33 pM, 380 pM and 35 pM, respectively. ITI-214 shows efficacy in various animal models of motor and cognitive functions.

Avanafil (TA-1790) is a potent and selective phosphodiesterase-5 (PDE-5) inhibitor with IC₅₀ values of 5.2 nM, 630 nM, 5700 nM, 6200 nM, 12000 nM, 27000 nM, 51000 nM and 53000 nM for PDE-5, PDE-6, PDE-4, PDE-10, PDE-8, PDE-7, PDE-2 and PDE-1, respectively. Avanafil activates NO/cGMP/PKG signaling-pathway to decrease loss in BMD, bone atrophy, and oxidative stress. Avanafil inhibits cyclic guanosine monophosphate (cGMP) hydrolysis and thus increases cGMP levels. Avanafil can be used for the research of erectile dysfunction and osteoporosis.

Vardenafil is a selective and orally active inhibitor of phosphodiesterase-5 (PDE5), with an IC₅₀ of 0.7 nM. Vardenafil shows inhibitory towards PDE1, PDE6 with IC₅₀s of 180 nM, and 11 nM, while IC₅₀s are >1000 nM for PDE3 and PDE4. Vardenafil competitively inhibits cyclic guanosine monophosphate (cGMP) hydrolysis and thus increases cGMP levels. Vardenafil can be used for the research of erectile dysfunction, hepatitis, diabetes^[1]-[6].

Piclamilast (RP 73401) is a phosphodiesterase 4 (PDE4) inhibitor, with IC₅₀ values of 16 nM and 2 nM in pig aorta and eosinophil soluble, respectively.

Olprinone (Loprinone) is a potent and selective phosphodiesterase 3 (PDE3) inhibitor, with IC₅₀ values of 150, 100, 0.35, and 14 μM against PDE1, PDE2, PDE3, and PDE4, respectively. Olprinone exerts comprehensive protective effects including anti-inflammatory, antioxidant, and anti-apoptotic activities by elevating intracellular cAMP levels and inhibiting the NF-κB and MAPK signaling pathways. Olprinone can be used in studies related to lung injury, spinal cord injury, myocardial ischemia-reperfusion injury, and cerebral ischemic injury.

Olprinone (Loprinone) Hydrochloride is a potent and selective phosphodiesterase 3 (PDE3) inhibitor, with IC₅₀ values of 150, 100, 0.35, and 14 μM against PDE1, PDE2, PDE3, and PDE4, respectively. Olprinone Hydrochloride exerts comprehensive protective effects including anti-inflammatory, antioxidant, and anti-apoptotic activities by elevating intracellular cAMP levels and inhibiting the NF-κB and MAPK signaling pathways. Olprinone Hydrochloride can be used in studies related to lung injury, spinal cord injury, myocardial ischemia-reperfusion injury, and cerebral ischemic injury.

Multitarget AD-IN-6 (Compound 39) is a multi-target inhibitor, with an IC₅₀ of 15.54 μM against PDE4B, 15.15 μM against PDE7A, 8.39 μM against PDE3A, and a K_d of 37.7 μM against CHIT1. Multitarget AD-IN-6 acts as a TRPA1 antagonist, reduces the level of the NLRP3 inflammasome multiprotein complex to inhibit its activation, while inhibiting PDE4B, PDE7A and CHIT1, and decreasing the phosphorylation of NF-κB. Multitarget AD-IN-6 improves the pathology of elastase-induced emphysema in mice. Multitarget AD-IN-6 is applicable for the research of chronic obstructive pulmonary disease.

Vardenafil hydrochloride is a selective and orally active inhibitor of phosphodiesterase-5 (PDE5), with an IC₅₀ of 0.7 nM. Vardenafil hydrochloride shows inhibitory towards PDE1, PDE6 with IC₅₀s of 180 nM, and 11 nM, while IC₅₀s are >1000 nM for PDE3 and PDE4. Vardenafil hydrochloride competitively inhibits cyclic guanosine monophosphate (cGMP) hydrolysis and thus increases cGMP levels. Vardenafil hydrochloride can be used for the research of erectile dysfunction, hepatitis, diabetes^[1]-[6].

NPD-001 is a potent Trypanosoma brucei phosphodiesterases 1/2 (TbrPDEB1/2) inhibitor, with IC₅₀ values of 4 and 3 nM, respectively. NPD-001 also inhibits hPDE4. NPD-001 can increase cAMP levels in parasites, prevent cytokinesis, and cause the parasites to form multinucleated, multi-flagellated cells that eventually lyse. NPD-001 can be used for the research of infection.

DSR-141562 is a novel, orally active, and selective brain-penetrant phosphodiesterase 1 (PDE1) inhibitor. DSR-141562 shows preferential selectivity for human PDE1B with an IC₅₀ of 43.9 nM, and the IC₅₀ values for human PDE1A and 1C are 97.6 and 431.8 nM, respectively. DSR-141562 can be used for the study of positive symptoms, negative symptoms and cognitive impairments associated with schizophrenia.

Osoresnontrine (BI-409306) is a potent and selective PDE9A inhibitor, with an IC₅₀ of 52 nM, and shows weak activity against other PDEs, such as PDE1A (IC₅₀, 1.4 µM), PDE1C (IC₅₀, 1.0 µM), PDE2A, PDE3A, PDE4B, PDE5A, PDE6AB, PDE7A, and PDE10A (IC₅₀ all > 10 μM); Osoresnontrine can be used in the research of memory enhancement in CNS disorders.

CD00509 is a tyrosyl-DNA phosphodiesterase (PDE) Tdp1 inhibitor with an IC₅₀ of 0.71 μM. CD00509 increases DNA damage and promotes apoptosis of MCF-7 cells. CD00509 can sensitize breast cancer cells and wild-type murine embryonic fibroblasts (MEFs) to Camptothecin (CPT) (HY-16560). CD00509 can be used for the study of cancers such as breast cancer.

Vardenafil hydrochloride trihydrate is a selective and orally active inhibitor of phosphodiesterase-5 (PDE5), with an IC₅₀ of 0.7 nM. Vardenafil hydrochloride trihydrate shows inhibitory towards PDE1, PDE6 with IC₅₀s of 180 nM, and 11 nM, while IC₅₀s are >1000 nM for PDE3 and PDE4. Vardenafil hydrochloride trihydrate competitively inhibits cyclic guanosine monophosphate (cGMP) hydrolysis and thus increases cGMP levels. Vardenafil hydrochloride trihydrate can be used for the research of erectile dysfunction, hepatitis, diabetes^[1]-[6].

TAK-915 is a potent, selective, brain-penetrant and orally active phosphodiesterase 2A (PDE2A) inhibitor with an IC₅₀ of 0.61 nM. TAK-915 is >4100-fold more selectivity for PDE2A than PDE1A. TAK-915 has the potential for neuropsychiatric and neurodegenerative disorders treatment.

PDE5-IN-7 (compound 8) is a selective phosphodiesterase 5 (PDE 5) inhibitor with an IC₅₀ value of 5 nM, while an IC₅₀ of 300 nM for PDE 1.

Gisadenafil besylate (UK 369003-26) is a specific, orally active phosphodiesterase 5 (PDE5) inhibitor with an IC₅₀ of 3.6 nM and prevents degradation of cyclic guanosine monophosphate (cGMP).

Tovinontrine (IMR-687) is a highly potent and selective phosphodiesterase-9 (PDE9) inhibitor specifically for the treatment of sickle cell disease. IC₅₀s are 8.19 nM and 9.99 nM for PDE9A1 and PDE9A2, respectively.

(S)-C33 is a potent and selective PDE9 (phosphodiesterase-9) inhibitor, with an IC₅₀ of 11 nM. (S)-C33 can be used for central nervous system diseases and diabetes research.

MBCQ is a potent and selective cGMP-specific phosphodiesterase (PDE V; PDE5) inhibitor with an IC₅₀ of 19 nM. MBCQ lacks inhibitory activity toward other PDE isozymes (all IC₅₀s>100 μM). MBCQ dilates coronary arteries via specific inhibition of cGMP-PDE.

PDE1-IN-9 (Compound 7a) is a selective inhibitor for phosphodiesterase 1 (PDE1), that inhibits PDE1C with an IC₅₀ of 11 nM. PDE1-IN-9 reduces mRNA expression of IL-1β, IL-6, TNF-α and iNOS, inhibits the production of nitric oxide (NO) and reactive oxygen species (ROS). PDE1-IN-9 exhibits good metabolic stability in rat liver microsomes.