PDE4
PDE4 (phosphodiesterase 4) is a cAMP-specific phosphodiesterase family that terminates intracellular cAMP signaling through hydrolysis of cyclic adenosine monophosphate, thereby regulating multiple inflammatory and immune responses[1][2]. PDE4-mediated control of cAMP signaling influences the activity of immune and resident tissue cells, including T lymphocytes, macrophages, monocytes, neutrophils, and epithelial cells, placing this enzyme family at the center of inflammatory signaling networks[1][3]. Mechanistically, inhibition of PDE4 elevates intracellular cAMP levels and suppresses the production and release of pro-inflammatory mediators, which has established PDE4 as a therapeutic target in chronic inflammatory diseases and experimental models of airway and immune dysfunction[1][3][4]. Disease relevance is supported by the clinical development and approval of PDE4 inhibitors for conditions such as chronic obstructive pulmonary disease, psoriatic arthritis, and atopic dermatitis, where modulation of inflammatory pathways contributes to therapeutic benefit[3][4]. Compared with related isoforms, the PDE4 family comprises four gene subfamilies, PDE4A, PDE4B, PDE4C, and PDE4D, with PDE4A, PDE4B, and PDE4D highly represented in immune cells, whereas PDE4C expression is generally limited in these cellular contexts[1]. Importantly, PDE4B has been associated with anti-inflammatory pharmacology, whereas PDE4D has been linked to nausea and emesis observed with nonselective PDE4 inhibition, motivating the development of subtype-selective inhibitors[3][5]. For experimental applications, inhibitors such as roflumilast, apremilast, and crisaborole are widely used to investigate cAMP-dependent regulation of inflammation and to evaluate isoform-selective pharmacological strategies[3][4].
References:
- [1]. Spina D. PDE4 inhibitors: current status. Br J Pharmacol. 2008 Oct;155(3):308-15. doi: 10.1038/bjp.2008.307. Epub 2008 Jul 28. PMID: 18660825; PMCID: PMC2567892. et al. PDE4 inhibitors: current status. Br J Pharmacol. 2008 Oct;155(3):308-15. [Content Brief]
- [2]. Jin J, et al. PDE4 Inhibitors: Profiling Hits through the Multitude of Structural Classes. Int J Mol Sci. 2023 Jul 15;24(14):11518. [Content Brief]
- [3]. Fan T, et al. PDE4 inhibitors: potential protective effects in inflammation and vascular diseases. Front Pharmacol. 2024 Jun 10;15:1407871. [Content Brief]
- [4]. Smith VB, et al. Selective phosphodiesterase 4 inhibitors in the treatment of allergy and inflammation. Curr Opin Investig Drugs. 2005 Nov;6(11):1136-41. [Content Brief]
- [5]. Blauvelt A, et al. Next Generation PDE4 Inhibitors that Selectively Target PDE4B/D Subtypes: A Narrative Review. Dermatol Ther (Heidelb). 2023 Dec;13(12):3031-3042. [Content Brief]
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PDE4 Related Products (198)
Related Products (198)
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S-Petasin
0 ImagesCat. No.: HY-N17617CAS No.: 70238-51-6S-Petasin is a phosphodiesterase (PDE) inhibitor with IC50 values of 25.5 μM and 17.5 μM for PDE3 and PDE4, respectively. S-Petasin inhibits cholesterol side-chain cleavage enzyme, 11β-hydroxylase, PPAR-γ, and iNOS induction at RNA and protein levels. S-Petasin induces apoptosis, activates caspases, cleaves PARP, modulates mitochondrial membrane permeability, and regulates BCL2/BAX, p53, Bcl-XL, MMP-2, MMP-9, p21, CDK4, and cyclin D1 expression. S-Petasin reduces inflammatory cell accumulation, cytokine and IgE levels, and enhances serum IgG2a levels. S-Petasin relaxes isolated sensitized guinea pig trachealis and exhibits gastrointestinal anti-spasmodic activity. S-Petasin reduces tonsillitis severity and asthmatic attack frequency. S-Petasin can be used for the research of prostate cancer, obesity, melanoma, allergic asthma, asthma, and peritonitis.
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Fenspiride
0 ImagesFenspiride, an orally active non-steroidal antiinflammatory agent, is an antagonist of H1-histamine receptor. Fenspiride inhibites phosphodiesterase 3 (PDE3), phosphodiesterase 4 (PDE4) and phosphodiesterase 5 (PDE5) activities with -log IC50 values of 3.44, 4.16 and approximately 3.8, respectively. Fenspiride can be used for the research of respiratory diseases.
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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.
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PDE4-IN-5
0 ImagesCat. No.: HY-144265CAS No.: 2768626-06-6PDE4-IN-5 (compound 33a) is a potent and selective PDE4 inhibitor (IC50=3.1 nM). PDE4-IN-5 has favorable skin permeability and a well-characterized binding mechanism. Anti-psoriasis effect.
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Mesembranol
0 ImagesCat. No.: HY-N17247CAS No.: 23544-42-5Synonyms: (-)-MesembranolMesembranol ((-)-Mesembranol) is a mesembrine-type alkaloid and serotonin reuptake inhibitor. Mesembranol can be found in Sceletium tortuosum and exhibits phosphodiesterase 4 (PDE4) inhibition. Mesembranol contributes to the psychoactive properties of Sceletium tortuosum. Mesembranol can be used for the research of central nervous system-related conditions.
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PDE4B/D-IN-5
0 ImagesCat. No.: HY-182060CAS No.: 3064814-26-9PDE4B/D-IN-5 (Compound P32) is a peripherally restricted, oral active inhibitor of PDE4B and PDE4D with extremely low blood-brain barrier penetration, with IC50 values of 3.4 nM and 2.2 nM, respectively. PDE4B-IN-8 inhibits the production of TNF-α. PDE4B/D-IN-5 significantly reduces the Bax/Bcl2 ratio, and alleviates oxidative stress by decreasing MPO activity and NO levels. PDE4B/D-IN-5 exhibits anti-inflammatory, antioxidant, and anti-apoptotic activities. PDE4B/D-IN-5 can be used for the research of acute lung injury.
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KW-4490
0 ImagesCat. No.: HY-19390CAS No.: 260561-48-6KW-4490 is a selective phosphodiesterase 4 (PDE4) inhibitor. KW-4490 can be used for the researches of inflammation and immunology, such as asthma.
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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.
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PDE4-IN-8
0 ImagesCat. No.: HY-144684CAS No.: 2415085-45-7PDE4-IN-8 (Example 5) is a potent PDE4 inhibitor with an IC50 of 0.93 nM for PDE4B2.PDE4-IN-8 has little effect on IL13 (IC50=4.04 nM), IL4 (IC50=36.33 nM), IFNy (IC50=2394 nM).
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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.
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Deacetylsclerotiorin
0 ImagesCat. No.: HY-126167CAS No.: 34696-50-9Deacetylsclerotiorin is a secondary metabolite of chloramphenicol isolated from the fungus Bartalinia robillardoides strain LF550. Deacetylsclerotiorin has significant inhibitory effects on Candida albicans (IC50=24 μM), Trichophyton rubrum (IC50=2.83 μM) and Septoria tritici (IC50=7..45 μM). In addition, Deacetylsclerotiorin also exhibits inhibitory effects on the enzyme phosphodiesterase 4 (PDE4) (IC50=2.8 μM).
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PDE4-IN-13
0 ImagesCat. No.: HY-155692PDE4-IN-13 is a PDE4 inhibitor with an IC50 of 1.56 μM. PDE4-IN-13 shows anti-inflammatory and antioxidant properties， and can be used for chronic obstructive pulmonary disease (COPD) research.
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Talaroterphenyl A
0 ImagesCat. No.: HY-163777Talaroterphenyl A (compound 1) is a p-terphenyl derivative present in the mangrove sediment-derived fungus Talaromyces sp. SCSIO 41412, which exhibits phosphodiesterase 4 (PDE4) inhibitory activity (IC50=1.2 μM). Talaroterphenyl A also exhibits anti-inflammatory and anti-fibrotic activities, significantly reducing the mRNA levels of pro-inflammatory cytokines IL-6, TNF-α, and IL-1β.
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PDE3/4-IN-2
0 ImagesPDE3/4-IN-2 is a dual PDE3A and PDE4B1 inhibitor, with an IC50 of 0.13 nM against PDE3A and 50 nM against PDE4B1. PDE3/4-IN-2 exhibits higher systemic exposure and longer retention time in lung tissues in ICR mice. PDE3/4-IN-2 can be used in research on respiratory diseases such as asthma and chronic obstructive pulmonary disease, as well as autoimmune inflammation-related studies.
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PDE3/4-IN-4
0 ImagesCat. No.: HY-181088CAS No.: 3088024-27-2PDE3/4-IN-4 is an orally active PDE3A and PDE4B inhibitor with IC50 values of 10 nM and 9.4 nM, respectively. PDE3/4-IN-4 shows selective activity relative to most other PDE family members. PDE3/4-IN-4 modulates the cAMP/PKA/CREB signaling pathway. PDE3/4-IN-4 inhibits pro-inflammatory factor IL-6. PDE3/4-IN-4 reduces expression of inflammatory markers in liver tissue. PDE3/4-IN-4 attenuates liver fibrosis. PDE3/4-IN-4 limits liver damage in cholestatic and sepsis-induced liver disease mice models. PDE3/4-IN-4 can be used for the research of liver injury, cholestatic liver diseases, sepsis-induced liver injury.
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PDE4B/7A-IN-1
0 ImagesPDE4B/7A-IN-1 is a dual PDE4B/PDE7A inhibitor. PDE4B/7A-IN-1 shows IC50 values of 69.0 μM for PDE4B and 57.0 μM for PDE7A, as well as Ki values of 539 nM for 5-HT1A and 328 nM for 5-HT7. PDE4B/7A-IN-1 shows favorable membrane permeability. PDE4B/7A-IN-1 can be used for the study of cognitive impairment and depression.
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AChE/PDE4-IN-1
0 ImagesCat. No.: HY-147846CAS No.: 3033234-46-4AChE/PDE4-IN-1 (compound 12c) is a potent and selective dual PDE4/AChE inhibitor, with IC50s of 0.28 μM and 1.88 μM for AChE and PDE4D, respectively. AChE/PDE4-IN-1 exhibits anti-neuroinflammatory effect for the research of Alzheimer's disease.
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PDE4B-IN-7
0 ImagesCat. No.: HY-181770CAS No.: 1226697-79-5PDE4B-IN-7 is a PDE-4B inhibitor with an IC50 of 160 nM. PDE4B-IN-7 can form a firm and stable binding with the active site of PDE-4B. PDE4B-IN-7 inhibits acetylcholine-induced bronchospasm in guinea pigs. PDE4B-IN-7 exerts activity against susceptible Gram-positive and Gram-negative bacterial strains. PDE4B-IN-7 can be used for the researches of asthma and bacterial agent.
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PDE4B/7A-IN-2
0 ImagesCat. No.: HY-146202CAS No.: 2511632-55-45-HT1A/5-HT7 receptor antagonist (5-HT1A Ki = 8 nM, Kb = 0.04 nM; 5-HT7 Ki = 451 nM, Kb = 460 nM) with PDE4B/PDE7A inhibitory activity (PDE4B IC50 = 80.4 μM; PDE7A IC50 = 151.3 μM) , its antidepressant like effect is stronger than that of escitalopram as a reference agent.
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Tofisopam (Standard)
0 ImagesTofisopam (Standard) is the analytical standard of Tofisopam (HY-A0165). This product is intended for research and analytical applications. 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.
