Moracin M derivative targeting PDE4 for the treatment of psoriasis DOI Creative Commons
Liru Chen, Deyan Wu,

Sen Wang

и другие.

Acta Materia Medica, Год журнала: 2025, Номер 4(2)

Опубликована: Янв. 1, 2025

Phosphodiesterase-4 (PDE4), a member of the phosphodiesterase superfamily, has highly important roles in cyclic nucleotide signaling pathways and variety skin disorders. Blocking PDE4 activity with inhibitors increases intracellular cAMP levels effectively relieves inflammatory phenotype psoriasis. However, traditional may cause adverse effects such as gastrointestinal reactions. Natural products typically exhibit safety profiles structural novelty, which are particularly advantageous for drug discovery. LW, derivative natural product Moracin M, was found to have favorable inhibitory (PDE4 IC 50 = 54 nM). Examination LW psoriasis treatment demonstrated good anti-inflammatory cellular models. In an imiquimod-induced mouse model, markedly improved psoriatic symptoms, evidenced by increased PASI scores ameliorated pathology. Moreover, significantly downregulated Inflammatory factors serum alleviated spleen damage. Therefore, substantial therapeutic potential, through decreasing factor ameliorating phenotypes. Our findings support potential candidate compound developing new treatments.

Язык: Английский

5‐hydroxymethylcytosine features of portal venous blood predict metachronous liver metastases of colorectal cancer and reveal phosphodiesterase 4 as a therapeutic target DOI Creative Commons
Nuo Xu, Zhaoya Gao, Deyan Wu

и другие.

Clinical and Translational Medicine, Год журнала: 2025, Номер 15(2)

Опубликована: Фев. 1, 2025

Abstract Metachronous liver metastases (MLM) are characterised by high incidence and mortality in clinical colorectal cancer treatment. Currently traditional methods cannot effectively predict prevent the occurrence of metachronous metastasis cancer. Based on 5hmC‐Seal analysis blood tissue samples, this study found that portal venous was more relevant to tumour gDNA than peripheral blood. We performed a novel epigenetic liquid biopsy strategy using 10 5hmC alterations, accurately distinguish MLM patients from without metastases. Among these phosphodiesterase 4 (PDE4D) highly increased correlated with poor survival. Moreover, our studies demonstrated PDE4D key metastasis‐driven target for drug development. Interfering function significantly repressed Similarly, roflumilast, PDE4 inhibitor chronic obstructive pulmonary disease (COPD) therapy, also inhibits Further indicate blocking can affect CRC invasion through HIF‐1α‐CCN2 pathway. To develop efficient reduce adverse events, we designed several new compounds based 2‐arylbenzofurans discovered lead L11 potent affinity significant suppression In work, provides promising predicting discovers as potential repurposed inhibiting metastasis, which have benefit future. Key points markers derived could promoted via The newly synthesised compound specifically inhibit abolish obvious toxic side effects.

Язык: Английский

Процитировано

2
Moracin M derivative targeting PDE4 for the treatment of psoriasis DOI Creative Commons
Liru Chen, Deyan Wu,

Sen Wang

и другие.

Acta Materia Medica, Год журнала: 2025, Номер 4(2)

Опубликована: Янв. 1, 2025

Phosphodiesterase-4 (PDE4), a member of the phosphodiesterase superfamily, has highly important roles in cyclic nucleotide signaling pathways and variety skin disorders. Blocking PDE4 activity with inhibitors increases intracellular cAMP levels effectively relieves inflammatory phenotype psoriasis. However, traditional may cause adverse effects such as gastrointestinal reactions. Natural products typically exhibit safety profiles structural novelty, which are particularly advantageous for drug discovery. LW, derivative natural product Moracin M, was found to have favorable inhibitory (PDE4 IC 50 = 54 nM). Examination LW psoriasis treatment demonstrated good anti-inflammatory cellular models. In an imiquimod-induced mouse model, markedly improved psoriatic symptoms, evidenced by increased PASI scores ameliorated pathology. Moreover, significantly downregulated Inflammatory factors serum alleviated spleen damage. Therefore, substantial therapeutic potential, through decreasing factor ameliorating phenotypes. Our findings support potential candidate compound developing new treatments.

Язык: Английский

Процитировано

0