IACS-13909

IACS-13909 is an allosteric inhibitor of Src homology region 2 domain-containing phosphatase 2 (SHP-2, IC50 = 11 nM). 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. 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.Formal Name: 1-[3-(2,3-dichlorophenyl)-1H-pyrazolo[3,4-b]pyrazin-6-yl]-4-methyl-4-piperidinamine. CAS Number: 2160546-07-4. Molecular Formula: C17H18Cl2N6. Formula Weight: 377.3. Purity: >98%. Formulation: (Request formulation change), A solid. Solubility: DMSO: Sparingly Soluble: 1-10 mg/ml, Ethanol: Sparingly Soluble: 1-10 mg/ml. SMILES: ClC1=CC=CC(C2=NNC3=NC(N4CCC(C)(CC4)N)=CN=C32)=C1Cl. InChi Code: InChI=1S/C17H18Cl2N6/c1-17(20)5-7-25(8-6-17)12-9-21-15-14(23-24-16(15)22-12)10-3-2-4-11(18)13(10)19/h2-4,9H,5-8,20H2,1H3,(H,22,23,24). InChi Key: AMADCPJVPLUGQO-UHFFFAOYSA-N.