GCN2 inhibitor APL-4098

An orally bioavailable inhibitor of the serine/threonine protein kinase general control nonderepressible 2 (GCN2; eukaryotic translation initiation factor 2-alpha kinase 4; GCN2 EIF2alpha kinase; eIF-2-alpha kinase GCN2), with potential antineoplastic and immunomodulating activities. Upon oral administration, GCN2 inhibitor APL-4098 specifically targets, binds to and inhibits the activity of GCN2. This prevents GCN2-mediated signaling and may induce apoptosis in tumor cells that rely on GCN2 signaling for survival. In addition, as GCN2 signaling reduces anti-tumor immunity, preventing GCN2 signaling may enhance anti-tumor immune responses. GCN2 plays a key role in the activation of the integrated stress response (ISR) pathway in response to amino acid deprivation and in hypoxic tumors.