Potent and selective first-in-class inhibitor of protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK or EIF2AK3) with IC50 value of 0.4 nM and >1000 fold selectivity over EIF2AK1 (HRI) and EIF2AK2 (PKR). Overall, good selectivity was observed, with only 20 protein kinases inhibited >85% by GSK 2606414 at 10 μM during screening against a panel of 294 kinases. It inhibits the growth of a human tumor xenograft in mice with good oral bioavailability and blood-brain barrier penetration.PERK is a type I ER membrane protein and one of three primary effectors of the unfolded protein response (UPR), which has a demonstrated role in tumor growth and angiogenesis.