Definition

An orally bioavailable inhibitor of the serine/threonine kinase protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK; eukaryotic translation initiation factor 2-alpha kinase 3; EIF2AK3; PEK), with potential antineoplastic activity. Upon oral administration, PERK inhibitor NMS-03597812 inhibits the activity of PERK. This prevents the activation of the PERK pathway and inhibits unfolded protein response (UPR) stress adaptation, which may lead to tumor cell apoptosis and the inhibition of tumor growth. PERK, one of the key sensors for the UPR, plays a key role in the response to and resolution of endoplasmic reticulum (ER) stress and also in tumor angiogenesis and survival.