Design and synthesis of selective degraders of EGFR mutant.
Basic Information
ID: ALA4680227
Journal: Eur J Med Chem
Title: Design and synthesis of selective degraders of EGFR mutant.
Authors: Zhang X,Xu F,Tong L,Zhang T,Xie H,Lu X,Ren X,Ding K
Abstract: A series of PROTAC (proteolysis targeting chimera) based selective EGFR (leucine 858 to arginine 858 mutation and threonine 790 to methionine 790) mutant degraders were designed and synthesized. One of the most potent compounds, 14o, effectively and selectively degraded EGFR with an DC value of 5.9 nM, while did not show obvious effect on the wild-type protein. Further mechanism investigation revealed that the degradation was mediated by ubiquitin proteasome pathway. Compound 14o could be utilized as an initial lead molecule for development of new EGFR degrader based therapy.
CiteXplore: 32171162
DOI: 10.1016/j.ejmech.2020.112199
Patent ID: ┄