Because nearly half of patients with PTPN11-mutated cancers bear strongly activating mutations of E76, D61, G60, and S502, an allosteric inhibitor would need to exhibit at least two additional orders of magnitude greater potency than SHP099 and a longer target residence time to achieve successful suppression of SHP2 activity of tumors bearing these mutations in a clinical setting17. This evidence concerns the gene PTPN11 and cancer.