ALK蛋白降解剂及其抗肿瘤应用

	ALK蛋白降解剂及其抗肿瘤应用
翻译题名	ALK PROTEIN DEGRADATION AGENT AND ANTI-TUMOR APPLICATION THEREOF
申请号	US16902172
	2020-10-01
公开（公告）号	US20200306273A1
公开日期	2020-10-01
摘要	本发明公开了式(I)化合物及其抗肿瘤用途。式(I)化合物对ALK靶蛋白具有降解和抑制作用。它们主要由四部分组成：第一部分ALK-TKI，是具有ALK酪氨酸激酶抑制活性的化合物；第二部分Lin是不同种类的接头(Linker)；第三部分ULM是具有VHL，CRBN或其它蛋白酶的泛素化的小分子配体(ULM，泛素连接酶结合部分)；和第四部分，基团A是羰基或不存在羰基，其将Alk-TKI共价键合到Lin上，其中Lin和ULm共价键合。本发明设计合成的一系列化合物具有广泛的药理活性，具有降解ALK蛋白和抑制ALK活性的作用，可用于相关肿瘤的治疗。
翻译摘要	A compound of formula (I) and its antitumor application are disclosed. The compounds of formula (I) have degradation and inhibitory effects on ALK target proteins. They are mainly composed of four parts : the first part, ALK-TKI, being compounds with ALK tyrosine kinase inhibitory activity; the second part, LIN, being different kinds of linker (Linker); the third part, the ULM, being a small molecule ligand (ULM, ubiquitin ligase binding moiety) with ubiquitination of VHL, CRBN or other proteases; and the fourth part, the group A, being a carbonyl group or absent, which covalently bond ALK-TKI to LIN, wherein LIN and ULM are covalently bonded. A series of compounds designed and synthesized by the present disclosure have wide pharmacological activities, have functions of degrading ALK protein and inhibiting ALK activity, and can be used for related tumor treatment.
当前权利人	Shanghaitech University
专利申请人	Shanghaitech University
	Xiaobao Yang; Biao Jiang; Xiaoling Song; Haifan Lin; Ning Sun; Jinju Chen; Xing Qiu; Chaowei Ren; Ying Kong
公开国别	美国
公开国别简称	US
IPC 分类号	A61K31//662; A61K31//4439; A61K31//454; A61K31//496; A61K31//501; A61K31//506; A61K31//519; A61P35//00
CPC分类号	A61P35//00; A61P35//02; C07D401//14; C07D405//14; C07D417//14; C07D487//04; C07F9//6561; A61K47//55; A61K31//506; A61K31//4025; A61K31//496; A61K31//519; A61K31//501; A61K31//53; A61K31//675; C07D417//12; C07F9//6558; A61K31//4439; A61K31//454; A61K31//662; A61K45//06
专利有效性	有效
专利类型	发明申请
专利类型字典	1
当前法律状态	授权
授权公告日	2023-10-03
授权公开（公告）号	US11771709B2
简单同族	EP3725771A4; JP2021506820A; KR1020200108838A; CA3085645A1; CN109912655B; CN109912655A; AU2018382122A1; AU2018382122B2; EP3725771A1; JP2022174114A; WO2019114770A1; US20200306273A1
扩展同族	JP2022174114A; EP3725771A1; US20200306273A1; JP2021506820A; CA3085645A1; EP3725771A4; AU2018382122B2; CN109912655B; WO2019114770A1; AU2018382122A1; CN109912655A; KR1020200108838A
INPADOC 同族	US20200306273A1; KR1020200108838A; EP3725771A4; AU2018382122B2; AU2018382122A1; WO2019114770A1; CN109912655A; CA3085645A1; EP3725771A1; JP2021506820A; CN109912655B; JP2022174114A
文献类型	专利
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/294775
专题	免疫化学研究所_特聘教授组_抗体化学实验室免疫化学研究所_特聘教授组_干细胞生物学实验室科技发展处生命科学与技术学院_博士生
作者单位	Shanghaitech University
推荐引用方式 GB/T 7714	Xiaobao Yang,Biao Jiang,Xiaoling Song,等. ALK蛋白降解剂及其抗肿瘤应用. US16902172[P]. 2020-10-01.