上海科技大学知识管理系统

Task : Provide ALK proteolytic agents and their use in cancer therapy.The compounds of the following formula (I) have degradation and inhibitory effects on ALK target proteins. The compounds of the formula (I) are mainly ALK-TKI, which is a compound having ALK tyrosine kinase inhibitory activity, LIN, which is a different type of linker, and ULM (ubiquitin ligase binding moiety), which is a small molecule ligand in which VHL, CRBN or other proteases are ubiquitinated, and are carbonyls or are absent, ALK-TKI, It consists of four portions with group A covalently bonded to LIN covalently bonded to ULM. A series of compounds designed and synthesized in the present disclosure have broad pharmacological activity, have ALK proteolytic and ALK activity inhibitory functions, and can be used in the treatment of associated tumors.[Selection Diagram]None

任务：提供ALK蛋白水解剂及其在癌症治疗中的用途。下式(I)化合物对ALK靶蛋白具有降解和抑制作用。 式(I)化合物主要是Alk-TKI， 它是具有ALK酪氨酸激酶抑制活性的化合物， Lin， 它是不同类型的连接器， ULM(泛素连接酶结合部分)，它是一种小分子配体，其中VHL，CRBN或其它蛋白酶被泛素化，并且是羰基或不存在ALK-TKI，它由四个部分组成，其中基团A共价键合到与ULM共价键合的LIN上。 本发明设计并合成的一系列化合物具有广泛的药理活性，具有ALK蛋白水解和ALK活性抑制作用，可用于相关肿瘤的治疗。