Zhang Zhiqi, Sun Dejuan, Yang Yueying, Abbas Samir Y, Li Hua, Chen Lixia
Wuya College of Innovation, Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang, China.
Organometallic and Organometalloid Chemistry Department, National Research Centre, Cairo, Egypt.
Expert Opin Ther Pat. 2025 Jan;35(1):7-16. doi: 10.1080/13543776.2024.2423010. Epub 2024 Nov 4.
UNC-51-like kinase 1/2 (ULK1/2) are serine/threonine kinases that play a crucial role in autophagy activation and maintaining cellular homeostasis. Given their broad physiological relevance, ULK1/2 are candidate targets for treating various diseases. In recent years, ULK1/2 inhibitors have made significant progress, and the highly potent ULK1/2 inhibitors have entered clinical trials.
This review aims to provide an updated analysis of patents describing ULK1/2 inhibitors and their potential therapeutic applications that were disclosed between 2019 and 2024.
Due to their crucial role in various diseases, the invention of small-molecule drugs targeting ULK1/2 is particularly important, especially in cancer treatment. Despite the great success of ULK1/2 inhibitors development, ULK1/2 inhibitors are ATP competitive inhibitors of aminopyrimidines currently, and most ULK1/2 inhibitors are still in the preclinical research stage, with only DCC-3116 entered clinical research. Therefore, developing highly selective ULK1/2 inhibitors with low side effects and high bioavailability remains a challenging and promising research direction.
UNC-51样激酶1/2（ULK1/2）是丝氨酸/苏氨酸激酶，在自噬激活和维持细胞稳态中起关键作用。鉴于其广泛的生理相关性，ULK1/2是治疗各种疾病的候选靶点。近年来，ULK1/2抑制剂取得了重大进展，高效的ULK1/2抑制剂已进入临床试验阶段。
本综述旨在对2019年至2024年间公开的描述ULK1/2抑制剂及其潜在治疗应用的专利进行更新分析。
由于ULK1/2在各种疾病中起关键作用，开发靶向ULK1/2的小分子药物尤为重要，尤其是在癌症治疗方面。尽管ULK1/2抑制剂的开发取得了巨大成功，但目前ULK1/2抑制剂是氨基嘧啶的ATP竞争性抑制剂，大多数ULK1/2抑制剂仍处于临床前研究阶段，只有DCC-3116进入了临床研究。因此，开发具有低副作用和高生物利用度的高度选择性ULK1/2抑制剂仍然是一个具有挑战性但充满希望的研究方向。
