The disclosure relates generally to alpha polyglutamated lometrexol, formulations containing liposomes filled with alpha polyglutamated lometrexol, methods of making the alpha polyglutamated lometrexol and liposome containing formulations, and methods of using polyglutamated alpha polyglutamated lometrexol and liposome containing formulations to treat hyperproliferative disorders (e.g., cancer) and disorders of the immune system (e.g., an autoimmune disease such as rheumatoid arthritis).