SHP836 is a SHP2 allosteric inhibitor, with an IC50 of 12 μM for the full length SHP2[1].
SHP836 stabilizes the active conformation of SHP2, in which the catalytic site is blocked and no longer accessible to substrate[1].
[1]. Liu WS, et al. Structure based design of selective SHP2 inhibitors by De novo design, synthesis and biological evaluation. J Comput Aided Mol Des. 2019 Aug;33(8):759-774. [2]. Garcia Fortanet J, et al. Allosteric Inhibition of SHP2: Identification of a Potent, Selective, and Orally Efficacious Phosphatase Inhibitor. J Med Chem. 2016 Sep 8;59(17):7773-82.