Jiangsu Key Laboratory of Drug Design and Optimization, Department of Medicinal Chemistry, School of Pharmacy, China Pharmaceutical University, Nanjing, 210009, PR China.
Center of Drug Screening & Evaluation, Wannan Medical College, Wuhu, Anhui, 241000, PR China.
Eur J Med Chem. 2024 Apr 15;270:116333. doi: 10.1016/j.ejmech.2024.116333. Epub 2024 Mar 22.
Cushing's syndrome (CS) is a complex disorder characterized by the excessive secretion of cortisol, with Cushing's disease (CD), particularly associated with pituitary tumors, exhibiting heightened morbidity and mortality. Although transsphenoidal pituitary surgery (TSS) stands as the primary treatment for CD, there is a crucial need to optimize patient prognosis. Current medical therapy serves as an adjunctive measure due to its unsatisfactory efficacy and unpredictable side effects. In this comprehensive review, we delve into recent advances in understanding the pathogenesis of CS and explore therapeutic options by conducting a critical analysis of potential drug targets and candidates. Additionally, we provide an overview of the design strategy employed in previously reported candidates, along with a summary of structure-activity relationship (SAR) analyses and their biological efficacy. This review aims to contribute valuable insights to the evolving landscape of CS research, shedding light on potential avenues for therapeutic development.
库欣综合征(CS)是一种复杂的疾病,其特征是皮质醇过度分泌,库欣病(CD)尤其与垂体瘤有关,表现出更高的发病率和死亡率。虽然经蝶窦垂体手术(TSS)是治疗 CD 的主要方法,但仍需要优化患者的预后。由于目前的医学治疗效果不理想且副作用不可预测,因此它只是一种辅助治疗方法。在本综述中,我们深入探讨了 CS 发病机制的最新研究进展,并通过对潜在药物靶点和候选药物的批判性分析,探讨了治疗选择。此外,我们还概述了以前报道的候选药物所采用的设计策略,总结了结构-活性关系(SAR)分析及其生物学功效。本综述旨在为 CS 研究的不断发展提供有价值的见解,为治疗开发指明潜在的途径。