Key Laboratory of Novel Targets and Drug Study for Neural Repair of Zhejiang Province, School of Medicine, Hangzhou City University, Hangzhou, 310015, Zhejiang Province, China; College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, Zhejiang Province, China.
The National Center for Drug Screening, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.
Bioorg Chem. 2024 Apr;145:107217. doi: 10.1016/j.bioorg.2024.107217. Epub 2024 Feb 16.
Intrinsically disordered proteins (IDPs) are characterized by their inability to adopt well-defined tertiary structures under physiological conditions. Nonetheless, they often play pivotal roles in the progression of various diseases, including cancer, neurodegenerative disorders, and cardiovascular ailments. Owing to their inherent dynamism, conventional drug design approaches based on structural considerations encounter substantial challenges when applied to IDPs. Consequently, the pursuit of therapeutic interventions directed towards IDPs presents a complex endeavor. While there are indeed existing methodologies for targeting IDPs, they are encumbered by noteworthy constrains. Hence, there exists an imminent imperative to investigate more efficacious and universally applicable strategies for modulating IDPs. Here, we present an overview of the latest advancements in the research pertaining to IDPs, along with the indirect regulation approach involving the modulation of IDP degradation through proteasome. By comprehending these advancements in research, novel insights can be generated to facilitate the development of new drugs targeted at addressing the accumulation of IDPs in diverse pathological conditions.
无规卷曲蛋白（IDPs）的特征是它们在生理条件下无法采用明确的三级结构。尽管如此，它们在各种疾病的发展中通常起着关键作用，包括癌症、神经退行性疾病和心血管疾病。由于其固有的动态性，基于结构考虑的传统药物设计方法在应用于 IDP 时遇到了重大挑战。因此，针对 IDP 的治疗干预措施的研究是一项复杂的工作。虽然确实存在针对 IDP 的现有方法，但它们受到显著限制。因此，迫切需要研究更有效和普遍适用的调节 IDP 的策略。在这里，我们概述了 IDP 研究的最新进展，以及通过蛋白酶体调节 IDP 降解的间接调节方法。通过了解这些研究进展，可以产生新的见解，以促进开发针对不同病理条件下 IDP 积累的新药。
