8WDO

Crystal structure of PDE4D complexed with DCN

Summary for 8WDO

• Entry DOI: 10.2210/pdb8wdo/pdb
• Descriptor: cAMP-specific 3',5'-cyclic phosphodiesterase 4D, MAGNESIUM ION, ZINC ION, ... (6 entities in total)
• Functional Keywords: pde4d, complex, inhibitor, hydrolase
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 2
• Total formula weight: 81307.20

Authors

Liu, J.Y.,Li, M.J.,Xu, Y.C. (deposition date: 2023-09-15, release date: 2024-08-28)

Primary citation

Gu, C.,Liu, J.,Qian, F.,Yu, W.,Huang, D.,Shen, J.,Feng, C.,Chen, K.,Li, Y.,Jiang, X.,Xu, Y.,Zhang, L.
Identification of Dihydrobenzofuran Neolignans as Novel PDE4 Inhibitors and Evaluation of Antiatopic Dermatitis Efficacy in DNCB-Induced Mice Model.
J.Med.Chem., 67:4855-4869, 2024

PubMed Abstract: Atopic dermatitis is a chronic relapsing skin disease characterized by recurrent, pruritic, localized eczema, while PDE4 inhibitors have been reported to be effective as antiatopic dermatitis agents. 3',4--dimethylcedrusin (DCN) is a natural dihydrobenzofuran neolignan isolated from with moderate potency against PDE4 (IC = 3.26 ± 0.28 μM) and a binding mode similar to that of apremilast, an approved PDE4 inhibitor for the treatment of psoriasis. The structure-based optimization of DCN led to the identification of that showed high inhibitory potency on PDE4 (IC = 0.17 ± 0.02 μM), good anti-TNF-α activity (EC = 0.19 ± 0.10 μM), remarkable selectivity profile, and good skin permeability. The topical treatment of resulted in the significant benefits of pharmacological intervention in a DNCB-induced atopic dermatitis-like mice model, demonstrating its potential for the development of novel antiatopic dermatitis agents.

PubMed: 38489246
DOI: 10.1021/acs.jmedchem.3c02424

Experimental method

X-RAY DIFFRACTION (1.67 Å)