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.[2][3] Through this mechanism, PDE2A influences diverse biological processes including synaptic plasticity, neuronal signaling, mitochondrial function, cardiac remodeling, and cellular stress responses.[3][4][5] Mechanistically, PDE2A controls localized cyclic nucleotide microdomains and thereby regulates downstream protein kinase signaling pathways that govern cellular adaptation and homeostasis.[3][5] 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.[6][7][8] Inhibition of PDE2 enhances neuronal cGMP signaling, promotes synaptic plasticity, and improves memory performance in preclinical studies. 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.[2][3] 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.[2][4] Notably, PDE2A2 localizes to mitochondria and regulates mitochondrial respiration, morphology, and mitophagy, distinguishing it from other PDE2A isoforms.[4][5] 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.[7]
References:
- [1]. Uniprotkb.
- [2]. Sciencedirect.topics.
- [3]. Zaccolo M, et al. cAMP and cGMP signaling cross-talk: role of phosphodiesterases and implications for cardiac pathophysiology. Circ Res. 2007;100(11):1569-1578.
- [4]. Acin-Perez R, et al. A phosphodiesterase 2A isoform localized to mitochondria regulates respiration[J]. Journal of Biological Chemistry, 2011, 286(35): 30423-30432.
- [5]. Baliga RS, et al. Phosphodiesterase 2 inhibition preferentially promotes NO/guanylyl cyclase/cGMP signaling to reverse the development of heart failure. Proc Natl Acad Sci U S A. 2018 Jul 31;115(31):E7428-E7437. [Content Brief]
- [6]. Bubb KJ, et al. Inhibition of phosphodiesterase 2 augments cGMP and cAMP signaling to ameliorate pulmonary hypertension. Circulation. 2014 Aug 5;130(6):496-507. [Content Brief]
- [7]. Ruan L, et al. Phosphodiesterase-2 Inhibitor Bay 60-7550 Ameliorates Aβ-Induced Cognitive and Memory Impairment via Regulation of the HPA Axis. Front Cell Neurosci. 2019 Oct 2;13:432. [Content Brief]
All Product Categories
-
PDE2 Related Products (51)
Related Products (51)
-
Thioquinapiperifil dihydrochloride
0 ImagesSynonyms: KF31327Thioquinapiperifil dihydrochloride (KF31327), a potent, selective and non-competitive phosphodiesterase-5 (PDE-5, IC50 of 0.074 nM) inhibitor, is used for sexual enhancement study.
-
T-0156
0 ImagesCat. No.: HY-105349CAS No.: 324572-93-2T-0156 is a potent and selective phosphodiesterase type 5 (PDE5) inhibitor. T-0156 specifically inhibits the hydrolysis of cyclic guanosine monophosphate (cGMP) by PDE5 in a competitive manner (IC50=0.23 nM). T-0156 inhibits PDE6 (IC50=56 nM) and has low potencies against PDE1, PDE2, PDE3, and PDE4 (IC50>10 μM). T-0156 enhances the nitric oxide (NO)/cGMP pathway.
-
PDM-631
0 ImagesCat. No.: HY-102043CAS No.: 2095312-08-4PDM-631 is a selective and orally active PDE2A inhibitor with blood-brain barrier penetration. PDM-631 exhibits potent inhibitory activity against human and rat recombinant PDE2A with IC50 values of 1.5 nM and 4.2 nM, respectively. PDM-631 increases cGMP levels in the rat cerebral cortex. PDM-631 can be used for the study of schizophrenia and neurodegenerative disorders.
-
PF-04822163
0 ImagesCat. No.: HY-120741CAS No.: 1798334-07-2PF-04822163 is an orally active, selective, and blood-brain barrier permeable PDE1 inhibitor with IC50 values of 2 nM, 2.4 nM, and 7 nM for PDE1A, PDE1B, and PDE1C respectively. PF-04822163 can be used in the research of attention deficit hyperactivity disorder or Parkinson's disease.
-
Avanafil dibenzenesulfonate
0 ImagesCat. No.: HY-18252ACAS No.: 330784-48-0Synonyms: TA1790 dibenzenesulfonateAvanafil (TA-1790) dibenzenesulfonate 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 dibenzenesulfonate activates NO/cGMP/PKG signaling-pathway to decrease loss in BMD, bone atrophy, and oxidative stress. Avanafil dibenzenesulfonate inhibits cyclic guanosine monophosphate (cGMP) hydrolysis and thus increases cGMP levels. Avanafil dibenzenesulfonate can be used for the research of erectile dysfunction and osteoporosis.
-
PDE5-IN-2
0 ImagesCat. No.: HY-112704CAS No.: 2244517-61-9PDE5-IN-2 is a potent, highly selective, and orally active PDE5 inhibitor, with an IC50 of 0.31 nM, less potently inhibits PDE2A, PDE10A, PDE4D2, and PDE6C, with IC50s of 106, 46, 43, 1.2 nM, respectively. Anti-pulmonary arterial hypertension activity.
-
OPC 33540
0 ImagesCat. No.: HY-112631CAS No.: 189362-27-4OPC-33540 is a highly selective and competitive PDE3 inhibitor with IC50 values of 0.32 nM (PDE3A) and 1.5 nM (PDE3B). OPC-33540 exhibits IC50s against PDE1, PDE2, PDE4, PDE5, and PDE7 of 42.9, 52.3, 100.8, 2.5, and 51.3 μM, respectively. OPC-33540 significantly enhances cAMP accumulation in platelets and effectively inhibits thrombin-induced platelet aggregation. OPC-33540 can be used in antithrombotic studies.
-
Thioquinapiperifil
0 ImagesCat. No.: HY-119611CAS No.: 220060-39-9Synonyms: KF31327 free baseThioquinapiperifil (KF31327 free base), a potent, selective and non-competitive phosphodiesterase-5 (PDE-5, IC50 of 0.074 nM) inhibitor, is used for sexual enhancement study.
-
PDE2A-IN-2
0 ImagesCat. No.: HY-180526CAS No.: 2055901-03-4PDE2A-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 .
-
PDE5-IN-13
0 ImagesCat. No.: HY-170435PDE5-IN-13 (Compound 14b) inhibits phosphodiesterase 5 (PDE5A) with an IC50 of 3 nM. PDE5-IN-13 is a potential candidate for PAH (pulmonary arterial hypertension) research. PDE5-IN-13 has high selectivity for targets over PDE1, PDE2, PDE3, PDE4, PDE7, PDE8, PDE9, PDE10, and PDE11. PDE5-IN-13 is orally active.
-
Multitarget AD-IN-6
0 ImagesCat. No.: HY-181762Multitarget 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.
-
PDE2-IN-1
0 ImagesCat. No.: HY-179337PDE2-IN-1 is a potent and orally active PDE2 inhibitor with an IC50 of 0.6 μM, demonstrating neuroprotective effects. PDE2-IN-1 modulates the PKA/CREB/BDNF signaling pathway by inhibiting PDE2. PDE2-IN-1 improves memory deficits and cognitive impairment in an okadai acid (OKA)-induced Alzheimer’s disease (AD) mouse model. PDE2-IN-1 can be used for the research of AD.
-
AN-2898
0 ImagesCat. No.: HY-111167CAS No.: 906673-33-4AN-2898 is a selective PDE4 inhibitor with IC50 of 0.027 μM over other phosphodiesterase enzymes, such as PDE1A, PDE2A and PDE3A. AN-2898 also potently inhibits PDE4 subtypes (PDE4B1, PDE4A1A and PDE4D2). AN-2898 significantly inhibits the production of TNF-α, IL-2, IFN-γ, IL-5 and IL-10. AN-2898 can be used for mild to moderate atopic dermatitis (AD) and psoriasis research.
-
PDE/TRPA1/CHIT1-IN-1
0 ImagesCat. No.: HY-179503PDE/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.
-
PDE2A-IN-1
0 ImagesCat. No.: HY-142660CAS No.: 2648290-28-0PDE2A-IN-1 is a phosphodiesterase 2A (PDE2A) inhibitor with an IC50 value of 1.3 nM.
-
LH17
0 ImagesCat. No.: HY-180803LH17, 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.
-
PDE4D inhibitor 1
0 ImagesCat. No.: HY-173290PDE4-IN-1 is a PDE4 inhibitor with high potency (IC50 : 8.6 nM) and selectivity over other PDE subtypes. PDE4-IN-1 inhibits the release of inflammatory cytokines and chemokines. PDE4-IN-1 greatly restores impaired cAMP-CREB signaling pathway. PDE4-IN-1 inhibits proliferation and promotes differentiation to reverse the formation of psoriasis.
-
SLU-12091
0 ImagesCat. No.: HY-189060CAS No.: 3065124-09-3SLU-12091 is a phosphodiesterase (PDE) inhibitor and the more potent enantiomer of rac-11. SLU-12091 inhibits the activities of hPDE5, hPDE11, hPDE2A1, hPDE3A, hPDE3B, hPDE4A1A and hPDE4D2. SLU-12091 inhibits the growth of Cryptosporidium parvum without inhibiting the growth of host cells at the highest concentration tested. SLU-12091 can be used for the research of cryptosporidiosis.
-
Olprinone hydrochloride hydrate
0 ImagesCat. No.: HY-14254BCAS No.: 2072803-95-1Synonyms: Loprinone hydrochloride hydrateOlprinone (Loprinone) hydrochloride hydrate 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 hydrate 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 hydrate can be used in studies related to lung injury, spinal cord injury, heart failure, myocardial ischemia-reperfusion injury, and cerebral ischemic injury.
