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SHP099 is a potent, selective, orally bioavailable, and efficacious SHP2 inhibitor with IC50 =0.07 μM and p-ERK modulation in cells IC50 = 0.250 μM. SHP099 exhibits dose-dependent pathway inhibition and antitumor activity in xenograft models. SHP2 is a nonreceptor protein tyrosine phosphatase (PTP) encoded by the PTPN11 gene involved in cell growth and differentiation via the MAPK signaling pathway. SHP2 also purportedly plays an important role in the programmed cell death pathway (PD-1/PD-L1). Because it is an oncoprotein associated with multiple cancer-related diseases, as well as a potential immunomodulator, controlling SHP2 activity is of significant therapeutic interest.