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 (197)
Related Products (197)
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Catramilast
0 ImagesCat. No.: HY-14918CAS No.: 183659-72-5Catramilast is a PDE4D inhibitor. Catramilast can be used in pain research.
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Z21115
0 ImagesCat. No.: HY-161936CAS No.: 2958668-54-5Z21115 is an orally active inhibitor for phosphodiesterase 4 (PDE4), that inhibits PDE4D7 with IC50 of 10.5 nM. Z21115 inhibits Lipopolysaccharide (HY-D1056)-induced expression of IL-6, TNF-α and iNOS. Z21115 exhibits anti-inflammatory activity in DSS (HY-116282)-induced mouse colitis models without significant toxicity (1 g/kg).
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L-869298
0 ImagesCat. No.: HY-122167CAS No.: 362718-73-8L-869298 is a potent and selective PDE4 inhibitor with an IC50 of 0.5 nM for PDE4A. L-869298 shows less active against hERG potassium channel.
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AhR/PDE4 modulator-1
0 ImagesCat. No.: HY-189218AhR/PDE4 modulator-1 is a AhR/PDE4D dual-target modulator, with an AhR agonistic EC50 of 0.11 μM and a PDE4D inhibitory IC50 of 2.12 μM. AhR/PDE4 modulator-1 activates the AhR-CYP1A1 signaling pathway, promotes AhR nuclear translocation, and upregulates downstream CYP1A1; it inhibits PDE4D activity, elevates intracellular cAMP levels, and activates the downstream cAMP-PKA-CREB signaling pathway. Topical administration of AhR/PDE4 modulator-1 exerts anti-inflammatory effects in the Imiquimod (HY-B0180)-induced psoriasis-like mouse model, alleviates epidermal hyperplasia and inflammatory infiltration, and suppresses the expression of IL-17A/F. AhR/PDE4 modulator-1 can be used in research related to psoriasis.
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PDE4/5-IN-1
0 ImagesCat. No.: HY-181774CAS No.: 1807631-43-1PDE4/5-IN-1 is a selective phosphodiesterase 4/5 (PDE4/5) dual inhibitor. PDE4/5-IN-1 functionally inhibits PDE5, PDE4B2, and PDE4D2 activity. PDE4/5-IN-1 relaxes isolated rat prostate tissue, enhances nitric oxide-induced relaxation in isolated rat prostate tissue, and reduces alpha-1 adrenoceptor-mediated contractile responses in isolated rat prostate tissue. PDE4/5-IN-1 inhibits proliferation of human hyperplastic prostate cells. PDE4/5-IN-1 can be used for the research of benign prostatic hyperplasia.
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V11294
0 ImagesCat. No.: HY-182451CAS No.: 162278-10-6V11294 is a phosphodiesterase 4 (PDE4) inhibitor with a Ki value of 436 nM against human lung PDE4. V11294 exhibits anti-inflammation activity.
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PDE1-IN-4
0 ImagesCat. No.: HY-147946CAS No.: 3031349-98-8PDE1-IN-4 (compound 2g) is a potent and selective PDE1 (phosphodiesterase-1) inhibitor, with IC50 values of 10, 145, and 354 nM for PDE1C, PDE1A, and PDE1B, respectively. PDE1-IN-4 inhibits myofibroblast differentiation of human lung fibroblasts induced by TGF-β1. PDE1-IN-4 shows anti-fibrosis effects through the regulation of cAMP (3′,5′-cyclic adenosine monophosphate) and cGMP (3′,5′-cyclic guanosine monophosphate). PDE1-IN-4 can be used for idiopathic pulmonary fibrosis (IPF) research.
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BC-54
0 ImagesCat. No.: HY-124635CAS No.: 534579-04-9
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PDE4-IN-19
0 ImagesCat. No.: HY-159654CAS No.: 3042879-82-0PDE4-IN-19 (compound 1) is a PDE4 inhibitor, with IC50 values of <10 nM and 10-100 nM for PDE4B1 and PDE4D3, respectively.
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PDE4-IN-10
0 ImagesCat. No.: HY-147950CAS No.: 2413564-66-4PDE4-IN-10 (compound 7a) is a potent PDE4 inhibitor, with an IC50 of 7.01 μM for PDE4B. PDE4-IN-10 shows selectivity, microsomal stability, inhibition of TNF-α and no major toxicities in vitro.
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Ensifentrine tosylate
0 ImagesCat. No.: HY-119708ACAS No.: 3098314-20-3Synonyms: RPL-554 tosylateEnsifentrine (RPL-554) tosylate is an inhaled dual inhibitor of PDE3 and PDE4 with IC50s of 0.4 nM and 1479 nM, respectively. Ensifentrine tosylate blocks PDE3 and PDE4 enzymes, thereby increasing the levels of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) in lung cells, dilating the bronchi, and inhibiting the activation and migration of inflammatory cells. Ensifentrine tosylate can be used in the research of chronic obstructive pulmonary disease (COPD).
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Pumafentrine
0 ImagesCat. No.: HY-114766CAS No.: 207993-12-2Pumafentrine is an orally active, potent dual PDE3/PDE4 inhibitor. Pumafentrine dose-dependently ameliorates the clinical score and colonic TNFα production in murine Dextran sulphate sodium (DSS; HY-116282C)-induced colitis in a preventive setting.
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Girisopam
0 ImagesCat. No.: HY-187129CAS No.: 82230-53-3Girisopam is a PDE inhibitor with IC50 values of 3.2, 4.0, and 12.5 μM against PDE4, PDE2, and PDE5, respectively. Girisopam exhibits anxiolytic, antidepressant, anti-aggressive, and antipsychotic activities. The binding sites of Girisopam are enriched exclusively in the basal ganglia of rat brains, and depletion of these sites is associated with damage to the striatonigral pathway. Girisopam enhances the potency of μ-opioid receptor agonists, attenuates the antagonistic effect of low-dose Naloxone (HY-17417A), and synergistically potentiates the anti-fighting effect of Chlorpromazine (HY-12708). Girisopam can be used in studies related to psychiatric disorders such as anxiety and depression.
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Ronomilast
0 ImagesCat. No.: HY-15179CAS No.: 418794-42-0Synonyms: Elbimilast; ELB353Ronomilast (Elbimilast; ELB353) is an orally active phosphodiesterase-4 (PDE4) inhibitor with an IC50 of 3 nM. Revamilast can be used for research to inflammation related diseases.
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D-159404
0 ImagesCat. No.: HY-187591CAS No.: 1158221-32-9D-159404 is an orally active, blood-brain barrier-permeable, selective allosteric PDE4D inhibitor. It partially inhibits cAMP hydrolysis by binding to the UCR2 regulatory domain, elevates intracellular cAMP levels, and triggers calcium influx, thereby improving working memory and episodic memory consolidation. D-159404 is used in research on asthma, chronic obstructive pulmonary disease, and cognitive impairment.
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CP-220629
0 ImagesCat. No.: HY-129785CAS No.: 162141-96-0CP-220629 is a potent inhibitor of PDE4, with the IC50 of 0.44 μM. CP-220629 is efficacious in the guinea pig aerosolized antigen induced airway obstruction assay (ED50 2.0 mg/kg).
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CC-3052
0 ImagesCat. No.: HY-117954CAS No.: 216884-02-5CC-3052 is a phosphodiesterase 4 (PDE4) inhibitor with immunomodulatory activities. CC-3052 reduces neutrophil apoptosis in HIV⁺. CC-3052 is promising for research of HIV-related diseases.
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UK-500001
0 ImagesCat. No.: HY-119799CAS No.: 582332-31-8UK-500001 is an orally active inhibitor for phosphodiesterase 4 (PDE4), which inhibits PDE4D3 (IC50 is 0.28 nM), PDE4B2 (IC50 is 22.8 nM), PDE4A4 (IC50 is 26.1 nM) and PDE4C2 (IC50 is 271 nM). UK-500001 exhibits anti-inflammatory efficacy and inhibits TNF-α and IFN-γ release in human and rodent macrophagic cell lines in nanomolar levels. UK-500001 ameliorates chronic obstructive pulmonary disease (COPD) and asthma.
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AWD 12-281
0 ImagesSynonyms: GW 842470AWD 12-281 is an orally active and highly selective phosphodiesterase 4 (PDE4) inhibitor (IC50 = 9.7 nM). AWD 12-281 is used in the study of allergic dermatitis, asthma, chronic obstructive pulmonary disease (COPD), and allergic rhinitis.
