PDE2 Inhibitor

EHNA hydrochloride is a potent and selective dual inhibitor of cyclic nucleotide phosphodiesterase 2 (PDE2)(IC₅₀=4 μM) and adenosine deaminase (ADA). EHNA hydrochloride exerts a concentration inhibition of the cGMP-stimulated PDE II (cGs-PDE)(IC₅₀:0.8 μM (human), 2 μM (porcine myocardium)), but has smaller inhibitory effect on the unstimulated PDE2 activity. EHNA hydrochloride play roles in mediating diverse pharmacological responses, including antiviral, antitumour and antiarrhythmic effects.

Bay 60-7550 is a potent and selective PDE2 inhibitor with a K_i of 3.8 nM.

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.

PF-05180999 (PF-999) is a phosphodiesterase 2A (PDE2A) inhibitor, with an IC₅₀ of 1.6 nM.

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.

PF-05085727 is a potent, selective and brain penetrant inhibitor of cGMP-dependent PDE2A (IC₅₀=2 nM). PF-05085727 inhibits PDE2A >4,000-fold selectivity over PDE1 and PDE3-11.

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.

Aristolochic acid D (Aristolochic acid-IVa) is an orally active PDE2 (IC₅₀: 4.673 μM) and CDK2 (IC₅₀: 25 μM) inhibitor that can be isolated from Aristolochia indica L. Aristolochic acid D exhibits anti-inflammatory activity and is non-carcinogenic and non-nephrotoxic. Aristolochic acid D can be used in the research of inflammation and tumor-related diseases.

Morcamilast (ME3183) is a potent, orally active, selective phosphodiesterase 4 (PDE4) inhibitor, with IC₅₀ values of 1.28 nM, 2.33 nM and 1.63 nM against human PDE4A1A, PDE4B1 and PDE4D2, respectively. Morcamilast inhibits the production of TNF-α, IL-12/23p40, IL-23, IL-17A, IL-4, IL-5 and IL-13 in human PBMCs and T cells, and alleviates chronic Oxazolone (HY-126360)-induced dermatitis, Substance P (HY-P0201)-induced pruritus, Imiquimod (HY-B0180)-induced psoriasis-like dermatitis and LPS (HY-D1056)-induced arthritis. Morcamilast is used for the research of psoriasis, atopic dermatitis, psoriatic arthritis and other inflammatory and immune-related diseases.

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.

Tofisopam, a 2,3-benzodiazepine compound, is an orally active anxiolytic agent. Tofisopam can inhibit phosphodiesterase PDE isoenzyme activity, withIC₅₀ values of 2.11 μM, 1.98 μM, 0.42 μM, and 0.92 μM for PDE-2A3, PDE-3A, PDE-4A1, and PDE-10A1, respectively. Tofisopam can be used for the study of anxiety.

K134 is a phosphodiesterase 3 (PDE3) inhibitor. The IC₅₀s of K134 toward PDE3A, PDE3B, PDE5, PDE2 and PDE4 are 0.1, 0.28, 12.1, >300 and >300 µM, 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.

Hcyb1 is a highly selective, orally active PDE2 inhibitor. Hcyb1 has a highly selective inhibition of PDE2A (IC₅₀=0.57 μM) and over 250-fold selectivity against other recombinant PDE family members. Hcyb1 produces neuroprotective and antidepressant‐like effects most likely mediated by cAMP/cGMP-CREB-BDNF signaling.

PDE2A-IN-3 (Example Ic1) is a selective phosphodiesterase 2A (PDE2A) inhibitor with IC₅₀s of 69 nM and 1762 nM for PDE2A and PDE10, respectively. PDE2A-IN-3 can be used for the study of neurological and psychiatric disorders.

RS-25344 hydrochloride is a selective cAMP-phosphodiesterase 4 (PDE 4; PDE IV) inhibitor with an IC₅₀ of 0.28 nM in human lymphocytes. RS-25344 hydrochloride has only weak inhibitory effects on PDE I, II, III (IC₅₀ of >100 μM, 160 μM, 330 μM, respectively). RS-25344 hydrochloride has anti-inflammatory, memory- and cognition enhancing, and antineoplastic effects.