Discovery of Potent and Noncovalent Reversible EGFR Kinase Inhibitors of EGFR

Overview

Journal ACS Med Chem Lett

Publisher American Chemical Society

Specialty Chemistry

Date 2019 Jun 22

PMID 31223440

Citations 21

Authors

Qiannan Li

Tao Zhang

Shiliang Li

Linjiang Tong

Junyu Li

Zhicheng Su

Fang Feng

Deheng Sun

Yi Tong

Xia Wang

Zhenjiang Zhao

Lili Zhu

Jian Ding

Honglin Li

Hua Xie

Yufang Xu

Affiliations

Soon will be listed here.

Abstract

In this paper, we describe the discovery and optimization of a series of noncovalent reversible epidermal growth factor receptor inhibitors of EGFR. One of the most promising compounds, , inhibited the enzymatic activity of EGFR with an IC value of 2.2 nM. Cell proliferation assays showed that effectively and selectively inhibited the growth of EGFR-dependent cells. This series of compounds, which occupy both the ATP binding site and the allosteric site of the EGFR kinase, may serve as a basis for the development of fourth-generation EGFR inhibitors for L858R/T790M/C797S mutants.

Citing Articles

Design and investigation of novel iridoid-based peptide conjugates for targeting EGFR and its mutants L858R and T790M/L858R/C797S: an in silico study.

Das A, Biggs M, Hunt H, Mahabadi V, Goncalves B, Phan C Mol Divers. 2024; .

PMID: 39424745 DOI: 10.1007/s11030-024-11007-3.

Next-generation EGFR tyrosine kinase inhibitors to overcome C797S mutation in non-small cell lung cancer (2019-2024).

Das D, Xie L, Hong J RSC Med Chem. 2024; .

PMID: 39246743 PMC: 11376191. DOI: 10.1039/d4md00384e.

A Visual Analysis of the Research Dynamics in Resistance to EGFR Inhibitors for NSCLC.

Shao J, Gu Y, Guo R, Xu J Drug Des Devel Ther. 2024; 18:2571-2591.

PMID: 38947223 PMC: 11214774. DOI: 10.2147/DDDT.S465238.

Linking ATP and allosteric sites to achieve superadditive binding with bivalent EGFR kinase inhibitors.

Wittlinger F, Ogboo B, Shevchenko E, Damghani T, Pham C, Schaeffner I Commun Chem. 2024; 7(1):38.

PMID: 38378740 PMC: 10879502. DOI: 10.1038/s42004-024-01108-3.

Machine Learning-Based Virtual Screening and Identification of the Fourth-Generation EGFR Inhibitors.

Chang H, Zhang Z, Tian J, Bai T, Xiao Z, Wang D ACS Omega. 2024; 9(2):2314-2324.

PMID: 38250375 PMC: 10795152. DOI: 10.1021/acsomega.3c06225.

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