Pharmacological effects of GSK2656157, a novel PERK kinase inhibitor, on tumor growth and angiogenesis using DCE-MRI in pancreatic tumor model

Introduction: The eukaryotic initiation factor 2-alpha kinase 3 (EIF2AK3) or PERK is one of three mediators of the unfolded protein response signal transduction pathway. Activation of PERK has been shown to regulate angiogenesis (1). GSK2656157 is the first-in-class, small molecule inhibitor of PERK enzyme activity in cells with an IC50 in the range of 10-30 nM as reflected by inhibition of stress-induced PERK autophosphorylation. In this study, we investigated the pharmacological effect of GSK2656157 on tumor growth and angiogenesis using dynamic contrast enhanced MRI (DCEMRI) in the BxPc3 xenograft tumor model.