TY - JOUR
T1 - 靶向SHP2的变构抑制剂和PROTAC药物研究进展
AU - Jiang, Mengmeng
AU - Li, Xiaobo
AU - Zhou, Liying
AU - Dong, Lei
N1 - Publisher Copyright:
© 2024 China Biotechnology Press. All rights reserved.
PY - 2024/11/25
Y1 - 2024/11/25
N2 - The protein tyrosine phosphatase containing Src homology 2 (SH2) domain (SHP2) is the first oncogenic protein confirmed belong to the protein tyrosine phosphatase (PTP) family. It has the potential to regulate multiple signaling pathways, including RAS-RAF-ERK, PI3K-AKT, and JAK-STAT, making it an important target for anti-tumor drug discovery. SHP2 also plays a critical role in promoting tumor cell resistance and modulating immune cell function in the tumor microenvironment. The discovery of allosteric inhibitors has advanced the development of SHP2 drugs, with several allosteric inhibitor drugs currently in clinical trials as monotherapy or combination therapy. At the same time, proteolysis targeting chimeras (PROTACs), a novel drug design approach, are being widely used in the development of SHP2-targeting drugs. This article summarizes the clinical research results of allosteric inhibitors targeting SHP2, and outlines the progress of PROTAC-SHP2 drug development, with the aim of providing inspiration for the design and improvement of SHP2 drug molecules.
AB - The protein tyrosine phosphatase containing Src homology 2 (SH2) domain (SHP2) is the first oncogenic protein confirmed belong to the protein tyrosine phosphatase (PTP) family. It has the potential to regulate multiple signaling pathways, including RAS-RAF-ERK, PI3K-AKT, and JAK-STAT, making it an important target for anti-tumor drug discovery. SHP2 also plays a critical role in promoting tumor cell resistance and modulating immune cell function in the tumor microenvironment. The discovery of allosteric inhibitors has advanced the development of SHP2 drugs, with several allosteric inhibitor drugs currently in clinical trials as monotherapy or combination therapy. At the same time, proteolysis targeting chimeras (PROTACs), a novel drug design approach, are being widely used in the development of SHP2-targeting drugs. This article summarizes the clinical research results of allosteric inhibitors targeting SHP2, and outlines the progress of PROTAC-SHP2 drug development, with the aim of providing inspiration for the design and improvement of SHP2 drug molecules.
KW - Domain allosteric inhibitors
KW - Proteolysis targeting chimeras
KW - Src homology 2 (SHP2)
KW - The protein tyrosine phosphatase containing
UR - http://www.scopus.com/inward/record.url?scp=85212081018&partnerID=8YFLogxK
U2 - 10.13523/j.cb.2403023
DO - 10.13523/j.cb.2403023
M3 - 文章
AN - SCOPUS:85212081018
SN - 1671-8135
VL - 44
SP - 66
EP - 75
JO - China Biotechnology
JF - China Biotechnology
IS - 11
ER -