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A Novel HDAC6 Inhibitor Ameliorates Imiquimod-Induced Psoriasis-Like Inflammation in Mice

文献类型： 外文期刊

作者： Cao, Anqi 1 ; Li, Yurong 1 ; Feng, Yanqiao 2 ; Wang, Xiaoquan 1 ; Wei, Wenyu 3 ; Sun, Hongyan 4 ; Quan, Junmin 1 ;

作者机构： 1.Peking Univ, Shenzhen Grad Sch, State Key Lab Chem Oncogen, Guangdong Key Lab Chem Genom, Shenzhen 518055, Peoples R China

2.Inno Biopharmaceut Shenzhen Co Ltd, Shenzhen 518055, Peoples R China

3.Chinese Acad Agr Sci, Inst Agr Resources & Reg Planning, State Key Lab Efficient Utilizat Arable Land China, Beijing 100081, Peoples R China

4.City Univ Hong Kong, Dept Chem, Kowloon, 83 Tat Chee Ave, Hong Kong 999077, Peoples R China

5.City Univ Hong Kong, Ctr Superdiamond & Adv Films COSDAF, Kowloon, 83 Tat Chee Ave, Hong Kong 999077, Peoples R China

关键词： psoriasis; inflammation; HDAC6; MAPK; STAT3

期刊名称：MOLECULES （ 影响因子：4.6； 五年影响因子：5.0 ）

ISSN：

年卷期： 2025 年 30 卷 15 期

页码：

收录情况： SCI

摘要： Psoriasis is a chronic inflammatory skin disease characterized by abnormal proliferation of keratinocytes and infiltration of inflammatory cells. Significant challenges remain in developing effective and safe targeted therapies for psoriasis. Here, we reported the discovery of novel cystamine derivatives for the treatment of psoriasis. These compounds effectively attenuated LPS-induced inflammation in vitro, and the optimal candidate CS1 ameliorated imiquimod-induced psoriasis-like inflammation in mice. Mechanistically, CS1 bound and inhibited the deacetylase HDAC6, subsequently inhibited the AKT, MAPK, and STAT3 pathways, attenuated the hyperproliferation and altered differentiation of keratinocytes and reduced the infiltration of immune cells. These findings suggest that HDAC6 may serve as a potential target for drug development in the treatment of psoriasis.

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