SHP099

SHP099 (CAS No.: 1801747-42-1) is a potent, orally bioavailable allosteric inhibitor of the non-receptor protein tyrosine phosphatase SHP2, a critical regulator of receptor tyrosine kinase-mediated signaling and a key modulator of the RAS–ERK pathway. By stabilizing SHP2 in its auto-inhibited conformation, SHP099 effectively suppresses downstream signal transduction, thereby attenuating cellular proliferation and survival signals associated with oncogenic transformation. The compound exhibits inhibitory activity against both wild-type SHP2 and clinically relevant activating mutants, including D61Y, E69K, A72V, and E76K, with biochemical potencies spanning the nanomolar to low micromolar range. In cellular systems, SHP099 inhibits the growth of cancer cell lines such as MV4-11 and TF-1 at low micromolar concentrations, consistent with its ability to disrupt RAS–ERK signaling and receptor tyrosine kinase-driven oncogenic processes. It has also demonstrated efficacy in reducing tumor growth in preclinical models, supporting its utility as a tool compound for investigating SHP2-dependent signaling networks and therapeutic strategies targeting aberrant MAPK pathway activation. SHP099 is widely used in studies of signal transduction, cancer biology, and drug discovery, with experimental concentrations or dosing regimens typically optimized according to specific model systems and research objectives.