2. Signaling Pathways
  3. Metabolic Enzyme/Protease
  4. Phosphodiesterase (PDE)
  5. PDE2 Isoform

PDE2

Phosphodiesterase 2A (PDE2A) is a dual-substrate cyclic nucleotide phosphodiesterase that hydrolyzes both cAMP and cGMP and functions as a key regulator of intracellular cyclic nucleotide signaling networks.[1] A defining feature of PDE2A is its allosteric activation by cGMP through the GAF-B regulatory domain, which enhances catalytic activity and enables bidirectional crosstalk between cGMP and cAMP signaling pathways.[10][2] Through this mechanism, PDE2A influences diverse biological processes including synaptic plasticity, neuronal signaling, mitochondrial function, cardiac remodeling, and cellular stress responses.[2][3][4] Mechanistically, PDE2A controls localized cyclic nucleotide microdomains and thereby regulates downstream protein kinase signaling pathways that govern cellular adaptation and homeostasis.[2][4] In disease-related experimental models, altered PDE2A activity has been associated with heart failure, pulmonary hypertension, neurodegenerative disorders, and cognitive dysfunction, highlighting its importance in pathological cyclic nucleotide signaling.[5][6][7] Inhibition of PDE2 enhances neuronal cGMP signaling, promotes synaptic plasticity, and improves memory performance in preclinical studies.[8] Compared with related phosphodiesterase families, PDE2A is unique because cGMP stimulates rather than inhibits its catalytic activity, allowing it to function as a central mediator of cAMP-cGMP signaling integration.[10][2] The PDE2A gene generates multiple isoforms, including PDE2A1, PDE2A2, and PDE2A3, which differ primarily in their N-terminal targeting sequences and subcellular localization rather than catalytic properties.[10][3] Notably, PDE2A2 localizes to mitochondria and regulates mitochondrial respiration, morphology, and mitophagy, distinguishing it from other PDE2A isoforms.[3][4] For experimental applications, selective PDE2 inhibitors such as BAY 60-7550 are widely used to investigate cyclic nucleotide compartmentalization, neuroplasticity, cardiovascular signaling, and mitochondrial regulatory mechanisms.[6][8][9]

PDE2 Related Products (45):

Cat. No. Product Name Effect Purity
  • HY-103160A
    EHNA hydrochloride
    		Inhibitor 99.67%
    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.
  • HY-14992
    Bay 60-7550
    		Inhibitor 98.39%
    Bay 60-7550 is a potent and selective PDE2 inhibitor with a Ki of 3.8 nM.
  • HY-18252
    Avanafil
    		Inhibitor 98.66%
    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.
  • HY-111371
    PF-05180999
    		Inhibitor 99.96%
    PF-05180999 (PF-999) is a phosphodiesterase 2A (PDE2A) inhibitor, with an IC50 of 1.6 nM.
  • HY-12887
    Piclamilast
    		Inhibitor 99.74%
    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.
  • HY-180526
    PDE2A-IN-2
    		Inhibitor
    PDE2A-IN-2 is a selective and brain-penetrant PDE2A inhibitor (Ki = 5.49 nM and 100 > fold selectivity over other PDE isoforms). The 11C-labeled PDE2A-IN-2 serves as a positron emission tomography (PET) tracer for brain imaging in patients with neurodegenerative diseases. PDE2A-IN-2 educes the radiotracer signal in PDE2A-rich regions in vitro. PDE2A-IN-2 exhibits low binding affinity in vivo. PDE2A-IN-2 can be used for neurodegenerative diseases .
  • HY-181762
    Multitarget AD-IN-6
    		Inhibitor
    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 Kd 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.
  • HY-179503
    PDE/TRPA1/CHIT1-IN-1
    		Inhibitor
    PDE/TRPA1/CHIT1-IN-1 is a phosphodiesterases (PDEs), TRPA1, and hCHIT1 (KD of 37.7 μM) inhibitor. PDE/TRPA1/CHIT1-IN-1 is a broad-spectrum PDE inhibitor, potently targeting key isoforms including PDE4B, PDE7A, PDE3A, and PDE8A with IC50s of 15.54, 15.15, 8.39 and 16.46 μM. PDE/TRPA1/CHIT1-IN-1 suppresses NLRP3 inflammasome activation and inhibits NF-κB phosphorylation, downregulating the expression of pro-inflammatory genes (TNF-α and IL-6) in vivo. PDE/TRPA1/CHIT1-IN-1 can be used for chronic obstructive pulmonary disease (COPD) and related inflammatory lung disorders research.
  • HY-102050
    PF-05085727
    		Inhibitor 99.53%
    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.
  • HY-136637
    NPD-001
    		Inhibitor 98.11%
    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.
  • HY-N1465
    Aristolochic acid D
    		Inhibitor 99.74%
    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.
  • HY-14254A
    Olprinone
    		Inhibitor 99.58%
    Olprinone (Loprinone) is a potent phosphodiesterase (PDE) 3 inhibitor, with IC50s of 150, 100, 0.35 and 14 μM for PDE1, PDE2, PDE3 and PDE4, respectively. Olprinone is used for the research of heart failure due to its positive inotropic and vasodilative effects. Anti-inflammatory activity.
  • HY-155830
    Morcamilast
    		Inhibitor 98.92%
    Morcamilast (ME3183) is a selective and orally active PDE4 inhibitor, with IC50s of 1.28 nM (PDE4A1A), 2.33 nM (PDE4B1), and 1.63 nM (PDE4D2) respectively. Morcamilast shows weak inhibition of PDEs other than PDE4s Morcamilast is an anti-inflammatory agent and inhibits LPS (HY-D1056)-induced release of TNF-α, IL-12/23p40, IL-23, and IL-17A in human PBMCs and T cells. Morcamilast has antipruritic effect and can be used in the study of psoriasis, atopic dermatitis, and other inflammatory diseases.
  • HY-103493
    TAK-915
    		Inhibitor 99.57%
    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.
  • HY-A0165
    Tofisopam
    		Inhibitor 99.46%
    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.
  • HY-U00186
    K134
    		Inhibitor 99.76%
    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.
  • HY-124775
    (S)-C33
    		Inhibitor 99.46%
    (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.
  • HY-114672
    MBCQ
    		Inhibitor 99.80%
    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.
  • HY-132993
    Hcyb1
    		Inhibitor 98.20%
    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.
  • HY-U00427
    PDE2A-IN-3
    		Inhibitor 99.88%
    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.