Research Advances in the Study of EGFR Mutations Resistance and Its Small Molecule Inhibitors

doi:10.13523/j.cb.20191012

China Biotechnology

2019, Vol. 39

Issue (10): 97-104 DOI: 10.13523/j.cb.20191012

Research Advances in the Study of EGFR Mutations Resistance and Its Small Molecule Inhibitors

LI Wen¹,CHEN Jie¹,HU Wei-nan¹,QI Ya-yun¹,FU Yi-hong¹,LIU Jia-min¹,WANG Zhen-chao^1,^2,^3,^**(

),OUYANG Gui-ping^1,^3,^4,^**(

)

1 College of Pharmacy, Guizhou University, Guiyang 550025, China
2 State Key Laboratory of Efficacy and Utilization of Medicinal Plants, Guizhou Medical University, Guiyang 550014, China
3 Center for Research of Fine Chemicals, Guizhou University, Guiyang 550025, China
4 Center for Research of Fine Chemicals, Guizhou University, Guiyang 550025, China

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Abstract

Epidermal growth factor receptor (EGFR) is an important transmembrane receptor with tyrosine kinase activity, which is abnormally expressed in a variety of malignant tumors and closely related to the proliferation, differentiation, metastasis and other life activities of tumor cells. At present, EGFR has been considered as a target for the treatment of tumors, and the drugs targeting on EGFR are mainly divided into two categories, one is monoclonal antibody drugs, and the other is small molecular kinase inhibitors. Small molecule inhibitors are prone to lead to EGFR mutation and drug resistance, thus affecting their clinical application. These mutations occur mainly near the ATP-binding site of the tyrosine kinase region, which are mainly deletion mutations on exon 19 and point mutations on exons 18 and 21.The types of drug-resistant mutations of EGFR and the ways in which they interact with small molecule inhibitors have been reviewed, with a view to providing references for the subsequent research and development of EGFR targeted drugs.

Key words： EGFR EGFR small molecule inhibitors Resistance Interaction

Received: 02 March 2019 Published: 12 November 2019

ZTFLH:

Q814

Corresponding Authors: Zhen-chao WANG,Gui-ping OUYANG E-mail: wzc.4884@163.com;oygp710@163.com

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	Wen LI
	Jie CHEN
	Wei-nan HU
	Ya-yun QI
	Yi-hong FU
	Jia-min LIU
	Zhen-chao WANG
	Gui-ping OUYANG

Cite this article:

LI Wen,CHEN Jie,HU Wei-nan,QI Ya-yun,FU Yi-hong,LIU Jia-min,WANG Zhen-chao,OUYANG Gui-ping. Research Advances in the Study of EGFR Mutations Resistance and Its Small Molecule Inhibitors. China Biotechnology, 2019, 39(10): 97-104.

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https://manu60.magtech.com.cn/biotech/10.13523/j.cb.20191012 OR https://manu60.magtech.com.cn/biotech/Y2019/V39/I10/97

Fig.1 Exon structure of EGFR and somatic mutations within the tyrosine kinase domain of the gene^[22]

Fig.2 The structure of Gefitinib and the crystal structure of EGFR-Gefitinib^[26]

Table 1 Recent research on EGFR small molecule inhibitors

Fig.3 The structure of Erlotinib and the crystal structure of EGFR-Erlotinib^[27]

Fig.4 The structure of Afatinib and the crystal structure of EGFR-Afatinib

Fig.5 The structure of AZD9291 and the crystal structure of EGFR-AZD9291^[32]

Fig.6 The structure of WZ4002 and the crystal structure of EGFR-WZ4002^[34]

Fig.7 The structure of AC0010 and the crystal structure of EGFR-AC0010^[35]

Fig.8 The structure of EAI045 and the crystal structure of EGFR-EAI045^[36]


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