Selective inhibition of Tumor necrosis factor receptor-1 (TNFR1) for the treatment of autoimmune diseases

【作者】 Nan Zhang , Ziyi Wang , Yongxing Zhao

【期刊名】 Cytokine and Growth Factor Reviews

【影响因子】 2019年: 5.982

【作者单位】 Department of Pharmaceutics, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, Henan, PR China

【年，卷(期)：页码】2020,55:80-85

【关键词】 TNF-α, TNF receptors, TNF inhibitors, NF-κB, Inflammation

【摘要】Anti-TNF biologics have achieved great success in the treatment of autoimmune diseases and have been the most selling biologics on market. However, the anti-TNF biologics have shown some disadvantages such as poor efficacy to some patients and high risk of infection and malignancies during clinical application. Current anti-TNF biologics are antibodies or antibody fragments that bind to TNF-α and subsequently block both TNF-TNFR1 and TNF-TNFR2 signaling. Transgenic animal studies indicate that TNFR1 signaling is responsible for chronic inflammation and cell apoptosis whereas TNFR2 signaling regulates tissue regeneration and inflammation. Recent studies propose to selectively inhibit TNFR1 to enhance efficacy and avoid side effects. In this review, we introduce the biology of TNF-TNFR1 and TNF-TNFR2 signaling, the advantages of selective inhibition of TNF-TNFR1 signaling and research updates on the development of selective inhibitors for TNF-TNFR1 signaling. Antibodies, small molecules and aptamers that selectively inhibit TNFR1 have showed therapeutic potential and less side effects in preclinical studies. Development of selective inhibitors for TNFR1 is a good strategy to enhance the efficacy and reduce the side effects of anti-TNF inhibitors and will be a trend for next-generation of anti-TNF inhibitors.

【全文链接】https://doi.org/10.1016/j.cytogfr.2020.03.002