SHP099 hydrochloride (C09-1170-743)

SHP099 hydrochloride is a potent, selective and orally available SHP2 inhibitor with an IC 50 of 70 nMIn VitroThe X-ray co-crystal for SHP099 with SHP2 reveals a new interaction with the basic amine and the Phe113 backbone carbonyl. SHP099 shows inhibition of cell proliferation (KYSE-520 model) with an IC 50 of 1.4 μM. SHP099 shows high solubility and high permeability with no apparent efflux in Caco-2 cells. SHP099 concurrently binds to the interface of the N-terminal SH2, C-terminal SH2, and protein tyrosine phosphatase domains, thus inhibiting SHP2 activity through an allosteric mechanism. SHP099 suppresses RAS–ERK signalling to inhibit the proliferation of receptor-tyrosine-kinase-driven human cancer cells. MCE has not independently confirmed the accuracy of these methods. They are for reference only.In VivoAfter a single doses of 30 and 100 mg/kg (red and blue lines, respectively), dose-dependent exposure and modulation of the pharmacodynamic marker p-ERK is observed in the xenografts. A daily oral dose of 10 or 30 mg/kg yield 19% and 61% tumor growth inhibition, respectively. Tumor stasis is achieved at 100 mg/kg . MCE has not independently confirmed the accuracy of these methods. They are for reference only.Form:SolidIC50& Target:IC50: 70 nM (SHP2). Specification: 0.99 Molecular Formula: C16H20Cl3N5 Molecular Weight: 388.72 PubChem CID: 121241170