PMID- 32988341
OWN - NLM
STAT- MEDLINE
DCOM- 20210629
LR  - 20210629
IS  - 1875-533X (Electronic)
IS  - 0929-8673 (Linking)
VI  - 28
IP  - 19
DP  - 2021
TI  - Allosteric Inhibitors of SHP2: An Updated Patent Review (2015-2020).
PG  - 3825-3842
LID - 10.2174/1568011817666200928114851 [doi]
AB  - 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.
CI  - Copyright(c) Bentham Science Publishers; For any queries, please email at 
      epub@benthamscience.net.
FAU - Wu, Jingwei
AU  - Wu J
AD  - Tianjin Key Laboratory on Technologies Enabling Development of Clinical 
      Therapeutics and Diagnostics (Theranostics), School of Pharmacy, Tianjin Medical 
      University, No. 22, Qixiangtai Road, Heping District, Tianjin 300070, China.
FAU - Zhang, Huan
AU  - Zhang H
AD  - Department of Pharmacy, Tianjin Medical University General Hospital, Tianjin 
      300052, China.
FAU - Zhao, Guilong
AU  - Zhao G
AD  - The Institute of Drug Discovery and Development, Chinese Academy of Sciences, 
      Zhongshan 528400, China.
FAU - Wang, Runling
AU  - Wang R
AD  - Tianjin Key Laboratory on Technologies Enabling Development of Clinical 
      Therapeutics and Diagnostics (Theranostics), School of Pharmacy, Tianjin Medical 
      University, No. 22, Qixiangtai Road, Heping District, Tianjin 300070, China.
LA  - eng
GR  - 81773569/National Natural Science Foundation of China/
PT  - Journal Article
PT  - Review
PL  - United Arab Emirates
TA  - Curr Med Chem
JT  - Current medicinal chemistry
JID - 9440157
RN  - 0 (Enzyme Inhibitors)
RN  - EC 3.1.3.48 (Protein Tyrosine Phosphatase, Non-Receptor Type 11)
SB  - IM
MH  - Allosteric Site
MH  - Enzyme Inhibitors
MH  - Humans
MH  - Mutation
MH  - *Neoplasms
MH  - *Protein Tyrosine Phosphatase, Non-Receptor Type 11/genetics/metabolism
OTO - NOTNLM
OT  - PTPN11 gene
OT  - SHP2 inhibitor
OT  - allosteric
OT  - cancer
OT  - clinical trial.
OT  - combination therapy
EDAT- 2020/09/30 06:00
MHDA- 2021/06/30 06:00
CRDT- 2020/09/29 05:25
PHST- 2020/05/29 00:00 [received]
PHST- 2020/08/17 00:00 [revised]
PHST- 2020/08/25 00:00 [accepted]
PHST- 2020/09/30 06:00 [pubmed]
PHST- 2021/06/30 06:00 [medline]
PHST- 2020/09/29 05:25 [entrez]
AID - CMC-EPUB-110278 [pii]
AID - 10.2174/1568011817666200928114851 [doi]
PST - ppublish
SO  - Curr Med Chem. 2021;28(19):3825-3842. doi: 10.2174/1568011817666200928114851.