TABLE 2.

SHP2 small-molecule inhibitors.

SHP2 inhibitors	Characteristics	References
SHP099	Allosteric small-molecule inhibitor, which binds to a tunnel-like pocket formed by the confluence of three domains of SHP2	Chen et al., 2016; Fodor et al., 2018
SHP244	Allosteric small-molecule inhibitor, which binds and stabilizes the inactive, closed conformation of SHP2	Fodor et al., 2018
SHP389	Allosteric small-molecule inhibitor, which binds to a tunnel-like pocket formed by the confluence of three domains of SHP2 and modulates MAPK signaling in vivo	Bagdanoff et al., 2019
SHP394	Allosteric small-molecule inhibitor, an orally efficacious inhibitor of SHP2, with high lipophilic efficiency, improved potency, and enhanced pharmacokinetic properties	Sarver et al., 2019
MRC-4550	Allosteric small-molecule inhibitor, which targets phosphatase activity of SHP2	Nichols et al., 2018
RMC-4630	Allotropic selective inhibitor, which is being evaluated in a multi-cohort phase I/II clinical program	Moore et al., 2020
PCC0208023	Allosteric small-molecule inhibitor, which shows higher affinity with key residues in the SHP2 allosteric pocket	Chen et al., 2020
NSC-87877	Binds to the catalytic cracking of SHP1/2 PTP and inhibits EGF-induced Erk1/2 activation in vitro	Song et al., 2009; Shi et al., 2015
PHPS1	Effective cell permeation inhibitor, which shows efficacy in blocking the downstream signal pathway dependent on SHP2	Chen et al., 2018; Salem et al., 2018
Cefsulodin	Blocks SHP2-mediated signal transduction and proliferation of several cancer cell in vitro	He et al., 2015