Changping Laboratory, Beijing 102206, China.
Changping Laboratory, Beijing 102206, China.
Bioorg Med Chem. 2024 Dec 1;115:117967. doi: 10.1016/j.bmc.2024.117967. Epub 2024 Oct 26.
Immune-inflammatory diseases are a class of conditions with high prevalence that severely impact the quality of life. Current treatment strategies include immunosuppressants, glucocorticoids, and monoclonal antibodies. However, these approaches have certain limitations, such as poor membrane permeability, immunogenicity, and the requirement for injection in large molecule drugs. Small molecule compounds, on the other hand, suffer from issues like poor selectivity, inability to inhibit non-enzymatic functions, and biological compensation. These factors constrain the effectiveness of current therapeutic strategies in immune-inflammatory diseases. As a novel small molecule drug development technology, proteolysis-targeting chimeras (PROTACs) regulate protein levels by inducing interactions between target proteins and E3 ubiquitin ligases, leading to the selective degradation of target proteins. This technology has already shown promising therapeutic effects in the treatment of immune-inflammatory diseases. This review aims to comprehensively summarize the application of PROTAC technology in the field of immune inflammation and provide insights into its potential in treating immune-inflammatory diseases.
免疫炎症性疾病是一类具有高患病率的疾病，严重影响生活质量。目前的治疗策略包括免疫抑制剂、糖皮质激素和单克隆抗体。然而，这些方法存在一定的局限性，如大分子药物的膜通透性差、免疫原性和注射要求。小分子化合物则存在选择性差、不能抑制非酶功能和生物补偿等问题。这些因素限制了当前免疫炎症性疾病治疗策略的有效性。作为一种新型的小分子药物开发技术，蛋白水解靶向嵌合体（PROTACs）通过诱导靶蛋白与 E3 泛素连接酶之间的相互作用来调节蛋白水平，导致靶蛋白的选择性降解。该技术在治疗免疫炎症性疾病方面已显示出良好的治疗效果。本综述旨在全面总结 PROTAC 技术在免疫炎症领域的应用，并探讨其在治疗免疫炎症性疾病中的潜力。
