Ask about this productRelated genes to: Pde4d Blocking Peptide
- Gene:
- PDE4D NIH gene
- Name:
- phosphodiesterase 4D
- Previous symbol:
- DPDE3
- Synonyms:
- -
- Chromosome:
- 5q11.2-q12.1
- Locus Type:
- gene with protein product
- Date approved:
- 1992-06-08
- Date modifiied:
- 2018-07-11
Related products to: Pde4d Blocking Peptide
Related articles to: Pde4d Blocking Peptide
- : PDE4 is a key regulator of cAMP signaling and a clinically validated anti-inflammatory target; however, the use of PDE4 inhibitors is often limited by adverse effects such as nausea, vomiting, and diarrhea. The natural compound braylin was previously identified as a novel PDE4 inhibitor scaffold, exhibiting an IC of 0.96 µM. Using the PDE4-braylin co-crystal structure, we conducted structure-based design and optimization to enhance its potency. : A series of novel braylin derivatives was synthesized and characterized. Their inhibitory activities against PDE4D were evaluated via enzymatic assays, and binding thermodynamics were analyzed by isothermal titration calorimetry (ITC). Molecular modeling was used to predict binding modes, and anti-inflammatory effects were assessed in LPS-stimulated macrophages. : Structure-guided optimization yielded lead compound , which showed significantly improved PDE4D inhibition (IC = 67 nM) and high-affinity binding = 45 nM) as confirmed by ITC. also exhibited remarkable selectivity against PDE isoforms. Molecular simulations highlighted key interactions with Gln369 and hydrophobic residues in the PDE4 active site. In cellular assays, dose-dependently suppressed LPS-induced inflammation in macrophages at non-cytotoxic concentrations with efficacy comparable to roflumilast. : We developed , a potent and selective PDE4 inhibitor derived from natural braylin. It demonstrated promising in vitro anti-inflammatory activity and represents a valuable lead for further therapeutic development. - Source: PubMed
Publication date: 2026/04/23
Guo YongdanWang XueZhang FengZheng TianshenChen ZhuoWang SenYang GuofengWang HaiboYin WenboHuang ShuhengLuo Hai-BinHuang Yi-YouWu Deyan - Phosphodiesterase 4 (PDE4) enzymes regulate intracellular cyclic adenosine monophosphate (cAMP) and thereby influence multiple cancer-relevant processes. Metastasis and angiogenesis, which rely on coordinated cytoskeletal remodelling and integrin-mediated signalling are key determinants of cancer progression. We previously reported KTX207, a cereblon-based proteolysis-targeting chimera (PROTAC) that selectively degrade PDE4D shortforms and suppresses tumour cell proliferation. - Source: PubMed
Publication date: 2026/05/21
Zorn AlinaZhao YiGiblin AoifeBelka IgorTorres EduardoSwindlehurst CathyChan KyleStirling DavidBaillie George SSin Yuan Yan - Phosphodiesterase 4 (PDE4) is a validated target for chronic inflammatory diseases such as COPD, asthma, and psoriasis. Although four PDE4 inhibitors have received FDA approval (roflumilast, apremilast, crisaborole, and ensifentrine), all suffer dose-limiting gastrointestinal side effects due to insufficient PDE4B/PDE4D selectivity. Plant-derived natural products offer complementary chemical space for discovering inhibitors with novel binding modes and improved isoform selectivity. This review systematically surveys plant-derived PDE4 inhibitors reported from 1979 to 2024, spanning seven major scaffold classes: flavonoids (∼40%), terpenoids, coumarins, xanthones, benzofurans, fluorenones, and alkaloids. Structure-activity analyses reveal that hydroxylation patterns, C2C3 unsaturation, and B-ring substitution govern flavonoid potency. Structure-guided optimization of toddacoumalone ultimately yielded compound 33a (IC = 3.1 nM, PDE4D), the fluorenone selaginpulvilin K (IC = 11 nM, 30-909-fold family selectivity), and a semi-synthetic α-mangostin derivative (IC = 17 nM). Despite promising potencies, critical gaps persist in subtype selectivity profiling, pharmacokinetic characterization, and metabolic stability. We propose that integrating AI-guided optimization, structure-informed isoform-selective design, nanodelivery systems, and biotechnology-enhanced production can accelerate clinical translation of these scaffolds. - Source: PubMed
Publication date: 2026/05/19
Huang Hao - Cardiac ischemia-reperfusion (I/R) injury is a major contributor to morbidity following myocardial infarction. While PDE4D has been implicated in cerebral I/R injury, its role and regulatory mechanisms in the cardiac context remain unclear. - Source: PubMed
Publication date: 2026/04/06
Li BeibeiLiu Hui - A series of symmetric and asymmetric diarylpentanoids based on -isopropyl-4-piperidone were rationally designed and synthesized through a Claisen-Schmidt condensation reaction. This was done to investigate their potential as anticancer and anti-inflammatory agents. The synthesized compounds were evaluated for cytotoxic activity against the MCF-7 breast cancer cell line, as well as for nitric oxide inhibitory activity in LPS-stimulated RAW264.7 macrophages. Structure-activity relationship analysis revealed that the presence of electron-donating substituents and asymmetric aryl substitutions significantly enhanced biological activity. Among the synthesized derivatives, compound KB2d exhibited the strongest anticancer activity, with an IC value of 1.54 µM, while compound KB2c demonstrated promising anti-inflammatory activity, with an IC value of 2.51 µM. To understand the molecular basis of these activities, molecular docking simulations and 200 ns molecular dynamics were conducted on aromatase and PDE4D protein targets. The leading compound, KB2d, showed stable binding behavior, low ligand RMSD oscillations, and favorable binding free energy (Δ_bind ≈ -33 kcal mol) as calculated using the MM-PBSA method. These findings suggest that asymmetric -isopropyl-4-piperidone diarylpentanoids represent promising structural frameworks for the further development of anticancer and anti-inflammatory agents. - Source: PubMed
Publication date: 2026/05/01
Tran Huy-KhoaMai Truc-VyLe Van-DungMinh-An Tran-NguyenMai Dinh-TriTran Quoc-TuanQuyen Vu ThiNguyen Thanh-DanhDang Chi-Hien