State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases & Department of Orthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, China.
Joint Research Institution of Altitude Health, Targeted Tracer Research and Development Laboratory, Institute of Respiratory Health, West China Hospital, Sichuan University, Chengdu, 610041, China.
Eur J Med Chem. 2023 Nov 5;259:115683. doi: 10.1016/j.ejmech.2023.115683. Epub 2023 Jul 26.
Receptor-interacting protein kinase 2 (RIPK2) belongs to the receptor-interacting protein family (RIPs), which is mainly distributed in the cytoplasm. RIPK2 is widely expressed in human tissues, and its mRNA level is highly expressed in the spleen, leukocytes, placenta, testis, and heart. RIPK2 is a dual-specificity kinase with multiple domains, which can interact with tumor necrosis factor receptor (TNFR), and participate in the Toll-like receptor (TLR) and nucleotide-binding oligomerization domain (NOD) signaling pathways. It is considered as a vital adapter molecule involved in the innate immunity, adaptive immunity, and apoptosis. Functionally, RIPK2 and its targeted small molecules are of great significance in inflammatory responses, autoimmune diseases and tumors. The present study reviews the molecule structure and biological functions of RIPK2, and its correlation between human diseases. In addition, we focus on the structure-activity relationship of small molecule inhibitors of RIPK2 and their therapeutic potential in human diseases.
受体相互作用蛋白激酶 2（RIPK2）属于受体相互作用蛋白家族（RIPs），主要分布在细胞质中。RIPK2 在人体组织中广泛表达，其 mRNA 水平在脾脏、白细胞、胎盘、睾丸和心脏中高度表达。RIPK2 是一种具有多个结构域的双特异性激酶，可与肿瘤坏死因子受体（TNFR）相互作用，并参与 Toll 样受体（TLR）和核苷酸结合寡聚化结构域（NOD）信号通路。它被认为是参与固有免疫、适应性免疫和细胞凋亡的重要衔接分子。在功能上，RIPK2 及其靶向小分子在炎症反应、自身免疫性疾病和肿瘤中具有重要意义。本研究综述了 RIPK2 的分子结构和生物学功能及其与人类疾病的关系。此外，我们还重点介绍了 RIPK2 小分子抑制剂的构效关系及其在人类疾病中的治疗潜力。
