KPT 9274 ( ATG-019) (C09-0930-802)

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. Specification: 0.98 Molecular Formula: C35H29F3N4O3 Molecular Weight: 610.62 PubChem CID: 117779453 Isomeric SMILES: C1CN(CCC1(F)F)C(=O)C2=CC=C(C=C2)C3=CC(=C4C(=C3)C=C(O4)CNC(=O)/C=C/C5=CN=C(C=C5)N)C6=CC=C(C=C6)F Related Documents: https://ald-pub-files.oss-cn-shanghai.aliyuncs.com/aladdinsci/pdp/sds/1/K414012-SCI_a4b9775d43b56806bfe4a08c85476f1a.pdf