CRD-1367799

CRD-1367799 is a potent and selective small molecule inhibitor of **General Control Nondenegrable 2 (GCN2)** kinase, developed by Chordia Therapeutics. GCN2 is a key sensor in the **integrated stress response (ISR)** pathway that phosphorylates eIF2α in response to amino acid deprivation and other cellular stresses. In multiple myeloma (MM), CRD-1367799 has demonstrated significant antitumor efficacy and the ability to overcome resistance to proteasome inhibitors, such as bortezomib, particularly in cells harboring mutations in the PSMB5 gene. By inhibiting GCN2, the drug disrupts the adaptive stress response that cancer cells utilize to survive proteotoxic stress and nutrient scarcity, thereby inducing apoptosis. It is primarily being investigated for the treatment of hematological malignancies, with a focus on multiple myeloma.