产品描述:
IACS-13909 is an allosteric inhibitor of Src homology region 2 domain-containing phosphatase 2 (SHP-2; IC50 = 11 nM).{68738} It binds wild-type SHP-2 and SHP-2 containing a constitutively activating glutamate-to-lysine substitution at position 76 (SHP-2E76K; Kds = 49 and 211 nM, respectively). IACS-13909 decreases the levels of phosphorylated ERK in KYSE-520 esophageal squamous cell carcinoma cells (IC50 = 47 nM) but also inhibits human-ether-a-go-go (hERG) channels (IC50 = 180 nM in whole-cell patch-clamp assays using CHO cells). It decreases tumor volume without affecting body weight in an EGFR-overexpressing KYSE-520 mouse xenograft model when administered at a dose of 70 mg/kg per day.{68739} IACS-13909 (70 mg/kg per day) induces sustained reduction in tumor volume after dosing cessation in a non-small cell lung cancer (NSCLC) mouse xenograft model using H1975 cells expressing drug-resistant EGFRL858R/T790M/C797S.