Allosteric Inhibitors of SHP2: An Updated Patent Review (2015-2020)

doi:10.2174/1568011817666200928114851

	Allosteric Inhibitors of SHP2: An Updated Patent Review (2015-2020)
	Wu, Jingwei 1; Zhang, Huan 2; Zhao, Guilong 3,4; Wang, Runling 1
刊名	CURRENT MEDICINAL CHEMISTRY
	2021
卷号	28 期号:19 页码:3825-3842
关键词	SHP2 inhibitor PTPN11 gene allosteric cancer combination therapy clinical trial
ISSN号	0929-8673
DOI	10.2174/1568011817666200928114851
通讯作者	Zhao, Guilong(zhao_guilong@126.com) ; Wang, Runling(grunling@tmu.edu.cn)
英文摘要	Srchomology-2-domain-containing PTP 2 (SHP2) is a nonreceptor phosphatase encoded by the PTPN11 gene. Over expression of SHP2 is associated with various human diseases, such as Noonan syndrome, LEOPARD syndrome, and cancers. To overcome the shortcomings of existing orthosteric inhibitors, novel inhibitors targeting the allosteric site of SHP2 with high selectivity and low toxicity are under development. This paper reviews allosteric inhibitors of SHP2 published in patents from 2015 to 2020. The molecules are classified according to the chemical structure of the central core. SHP2 has long been considered as an 'undruggable' protein. Fortunately, a critical breakthrough was made by researchers from Novartis AG Ltd., who identified SHP099 as a highly potent, selective, soluble, and orally bioavailable SHP2 allosteric inhibitor. Currently, there are several allosteric inhibitors of SHP2 in clinical development. However, drug resistance is still a major challenge. The combination of SHP2 allosteric inhibitors and immunotherapy drugs or molecular targeted drugs is emerging as a promising therapeutic strategy against drug resistance.
资助项目	National Natural Science Foundation of China[81773569]
WOS关键词	PROTEIN-TYROSINE PHOSPHATASES ; 1B PTP1B INHIBITORS ; RHEUMATOID-ARTHRITIS ; DOMAIN ; IDENTIFICATION ; ASSOCIATION ; EXPRESSION ; INSIGHTS ; PTPN22 ; DRIVEN
WOS研究方向	Biochemistry & Molecular Biology ; Pharmacology & Pharmacy
语种	英语
出版者	BENTHAM SCIENCE PUBL LTD
WOS记录号	WOS:000663836500007
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/296837]
专题	中国科学院上海药物研究所
通讯作者	Zhao, Guilong; Wang, Runling
作者单位	1.Tianjin Med Univ, Sch Pharm, Tianjin Key Lab Technol Enabling Dev Clin Therape, 22 Qixiangtai Rd, Tianjin 300070, Peoples R China 2.Tianjin Med Univ, Dept Pharm, Gen Hosp, Tianjin 300052, Peoples R China 3.Chinese Acad Sci, Inst Drug Discovery & Dev, Zhongshan 528400, Peoples R China 4.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China
推荐引用方式 GB/T 7714	Wu, Jingwei,Zhang, Huan,Zhao, Guilong,et al. Allosteric Inhibitors of SHP2: An Updated Patent Review (2015-2020)[J]. CURRENT MEDICINAL CHEMISTRY,2021,28(19):3825-3842.
APA	Wu, Jingwei,Zhang, Huan,Zhao, Guilong,&Wang, Runling.(2021).Allosteric Inhibitors of SHP2: An Updated Patent Review (2015-2020).CURRENT MEDICINAL CHEMISTRY,28(19),3825-3842.
MLA	Wu, Jingwei,et al."Allosteric Inhibitors of SHP2: An Updated Patent Review (2015-2020)".CURRENT MEDICINAL CHEMISTRY 28.19(2021):3825-3842.