PROTAC small molecule, RET inhibitor and application thereof

The invention discloses a PROTAC small molecule, an RET inhibitor and an application of the RETAC small molecule and the RET inhibitor. The PROTAC micromolecule provided by the invention has a structure as shown in a formula I: # imgabs0 #, wherein E3ligand is a protein ligand in an E3 ubiquitin ligase complex, and is at least one of a Cerebron protein ligand or a VHL protein ligand; and the linker is a linking group. The PROTAC small molecule provided by the invention has excellent biological activity on a KIF5B-RET fusion gene, and also has better activity on solvent leading edge mutation (RET G810C). The PROTAC small molecule compound disclosed by the invention has a good application prospect in the aspect of RET mutation and/or fusion mediated diseases. 本发明公开了一种PROTAC小分子、RET抑制剂及其应用；本发明提供的PROTAC小分子具有式I所示的结构：#imgabs0#其中，E3ligase为E3泛素连接酶复合体中的蛋白配体，为Cereblon蛋白配体或VHL蛋白配体中的至少一种；linker为连接基团。本发明提供的PROTAC小分子对KIF5B-RET融合基因具有优异的生物活性，也对溶剂前沿突变(RET G810C)具有更好的活性。本发明的PROTAC小分子化合物在RET突变和/或融合的介导的疾病方面具有良好的应用前景。