The presently disclosed subject matter relates to metabolic reprogramming agents that decrease glutamine metabolism, glycolysis, and fatty acid synthesis, pharmaceutical compositions comprising at least one, at least two, or at least three metabolic reprogramming agents, and the use of those agents and compositions for treating metabolic reprogramming disorders, such as immune disorders (e.g., autoimmune diseases), inflammatory diseases, and transplant rejection, pathologies due to CNS inflammation due to infection and not involving infection, and neurodegenerative disorders.