当前位置： SCI文献检索 > EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY期刊下所有文献 > Discovery of potent epidermal growth factor receptor (EGFR) degraders by proteolysis targeting chimera (PROTAC).

Discovery of potent epidermal growth factor receptor (EGFR) degraders by proteolysis targeting chimera (PROTAC).

Abstract：

:Epidermal growth factor receptor (EGFR), a member of the HER family, is closely related to the development of multiple cancers. Herein, we report the discovery of small molecule EGFR degraders based on the proteolysis targeting chimera (PROTAC) strategy. In the present study, 13 EGFR degraders containing pyrido[3,4-d] pyrimidine moiety were designed and synthesized. Promising PROTACs 2 and 10 induced degradation of EGFR in HCC827 cells with the DC50 values of 45.2 and 34.8 nM, respectively. Cellular protein-controlling machinery ubiquitin proteasome system (UPS) was involved in the degradation process. Furthermore, the degraders 2 and 10 could significantly induce the apoptosis of HCC827 cells and arrest the cells in G1 phase. These findings demonstrated that compounds 2 and 10 could serve as effective EGFRdel19-targeting degraders in HCC827 cells. v.

journal_name

Eur J Med Chem

journal_title

European journal of medicinal chemistry

authors

Zhang H,Zhao HY,Xi XX,Liu YJ,Xin M,Mao S,Zhang JJ,Lu AX,Zhang SQ

doi

10.1016/j.ejmech.2020.112061

subject

Has Abstract

pub_date

2020-03-01 00:00:00

pages

112061

eissn

0223-5234

issn

1768-3254

pii

S0223-5234(20)30028-3

journal_volume

189

pub_type

杂志文章

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