AMG44

AMG44 is a potent and selective small molecule inhibitor of PKR-like endoplasmic reticulum kinase (PERK), also known as EIF2AK3. Developed by Amgen, it targets the unfolded protein response (UPR) pathway, which tumors often exploit to survive endoplasmic reticulum (ER) stress and evade the immune system. By blocking PERK activity, AMG44 prevents the phosphorylation of eIF2α, thereby inhibiting the adaptive stress response that promotes tumor cell survival and immune suppression. Preclinical evidence suggests that AMG44 can sensitize clear cell renal cell carcinoma (ccRCC) cells to ER stressors and VEGF inhibitors like cabozantinib. It is currently being explored in early-phase clinical research for the treatment of ccRCC and other solid tumors.