Validated phosphotyrosine‐mimetic fragments F1, F2, and F4 were incorporated into the pyrazolone scaffold of the SHP2‐specific inhibitor GS493 and yielded nanomolar inhibitors of SHP2 that were able to block the Raf‐Erk‐Map signaling pathway in HGF‐activated cancer cells. The gene discussed is PTPN11; the disease is cancer.