GSK2656157 is a potent and selective inhibitor of PERK (protein kinase RNA-like endoplasmic reticulum kinase), a key component of the unfolded protein response (UPR) pathway. It has been primarily investigated for its potential in oncology, particularly in disrupting tumor cell survival mechanisms under endoplasmic reticulum stress. By inhibiting PERK, GSK2656157 prevents the downstream signaling that helps cancer cells adapt to stress conditions such as hypoxia and nutrient deprivation, commonly found in solid tumors. This leads to increased cancer cell death and reduced tumor growth in preclinical models. The compound has shown activity in various cancer types, including multiple myeloma, pancreatic cancer, and other solid tumors, especially when used in combination with agents that induce ER stress. Its application is also explored in modulating the tumor microenvironment, as PERK inhibition can affect angiogenesis and immune cell function. Due to its mechanism, GSK2656157 serves as a valuable tool compound in research focused on UPR pathways and is being studied to identify patient populations and tumor types most likely to benefit from PERK inhibition.