1ST-206

1ST-206 is a small molecule inhibitor of General Control Nonderepressible 2 (GCN2) kinase, currently in the discovery stage of development by First Biotherapeutics for the treatment of various cancers. GCN2, also known as EIF2AK4, is a key metabolic sensor that is activated by amino acid deprivation. Once activated, GCN2 phosphorylates the alpha subunit of eukaryotic initiation factor 2 (eIF2α), triggering the integrated stress response (ISR). This pathway allows tumor cells to adapt to nutrient-poor microenvironments and promotes the expression of genes involved in amino acid biosynthesis and transport, such as ATF4. Furthermore, GCN2 signaling in the tumor microenvironment can contribute to immunosuppression. By inhibiting GCN2, 1ST-206 is designed to disrupt these survival mechanisms, making tumor cells more susceptible to metabolic stress and potentially enhancing anti-tumor immune activity.