Description
InformationKPT 9274 ( ATG-019) KPT 9274 ( ATG-019) is an orally bioavailable small molecule that is a non-competitive dual inhibitor of PAK4 and NAMPT. It shows an IC50 of ~120 nM for NAMPT in a cell-free enzymatic assay.TargetsPAK4 (Cell-free assay); NAMPT (Cell-free assay) ; ~120 nMIn vitroKPT-9274 interferences with PAK4 and NAD biosynthetic pathways results in reduction of G2/M transit as well as induction of apoptosis and decrease in cell invasion and migration in several human RCC cell lines. The inhibition of the PAK4 pathway by KPT-9274 attenuates nuclear β-catenin as well as the Wnt/β-catenin targets cyclin D1 and c-Myc.In vivoKPT-9274 administration to a 786-O (VHL-mut) human RCC xenograft model leads to dose-dependent inhibition of tumor growth with no apparent toxicity. It also shows remarkable anti-tumor activity in sub-cutaneous xenograft models of pancreatic ductal adenocarcinoma (PDAC) cell lines and cancer stem cells as a single agent. KPT-9274 possesses desirable PK properties and is well tolerated in mice with the absence of any signs of toxicity when 200 mg/kg daily is administered either intravenously or orally.Cell Research(from reference)Cell lines：786-0, ACHN, Caki-1 and U-2 OS cells Concentrations：1µM and 5µM Incubation Time：12 hours