哈卡特
银屑病
肿瘤坏死因子α
药理学
医学
炎症
体内
免疫学
癌症研究
体外
化学
生物
生物化学
生物技术
作者
Ruiyu Xiang,Libo Hu,Siyuan Liu,Ziyu Wei,Zhen Song,Zhiming Chen,Yihe Liu,Juan Liu,Xiaoguang Lei,Yong Yang
标识
DOI:10.1016/j.jdermsci.2022.05.006
摘要
Background TNF-α elicits a cascade amplification effect in psoriasis. Macromolecule drugs targeting TNF-α are widely used for the clinical treatment of psoriasis. However, there are currently no effective small-molecule inhibitors that can be used in the clinic. Objective Novel TNF-α inhibitor was identified via high-throughput screening (HTS) and its anti-inflammatory activity was evaluated. Methods Two cell death models were established to identify inhibitors of TNF-α through HTS from a library of 3256 compounds. The effect of the inhibitor of TNF-α was tested by HaCaT cells in vitro and IMQ-induced psoriasis-like mouse model in vivo. Results Tiamulin fumarate (TF) was identified as an effective inhibitor of TNF-α. TF significantly blocked the NF-κB and MAPK signaling pathways in TNF-α-stimulated HaCaT cells. Additionally, systemic and topical administration of TF improved IMQ-induced psoriasis-like dermatitis in the mouse model. Conclusion Our study established a HTS method to identify TF as an inhibitor of TNF-α. The protective roles of TF in psoriasis-related inflammation reveal the potential therapeutic value of TF for psoriasis.
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