Abstract: The present disclosure provides methods for treating cancer comprising administering to a subject in need thereof a therapeutically effective amount of a dihydroorotate dehydrogenase (DHODH) inhibitor, wherein the cancer has an altered glutathione peroxidase 4 (GPX4) expression as compared to a control sample. The present disclosure also provides methods of treating a subject with a dihydroorotate dehydrogenase (DHODH) inhibitor where the subject's GPX4 expression is low as compared to a control sample or with a DHODH inhibitor and a ferroptosis inducer where the subject's GPX4 expression is high as compared to a control sample.

Abstract: Provided are methods of treating infectious diseases in mammals comprising administering a compound that inhibits glucose uptake. Particular infectious diseases that may be treated include malaria, leishmaniasis, African trypanosomiasis, tuberculosis, HIV, HCMV or herpes virus. In a first aspect, the invention features a method of treating infectious diseases in a mammal, comprising administering to a mammalian subject in need thereof a therapeutically effective amount of a compound or prodrug thereof, or pharmaceutically acceptable salt or ester of said compound or prodrug, wherein the compound is an inhibitor of glucose uptake.

Abstract: Provided are methods of treating infectious diseases in mammals comprising administering a compound that inhibits glucose uptake. Particular infectious diseases that may be treated include malaria, leishmaniasis, African trypanosomiasis, tuberculosis, HIV, HCMV or herpes virus. In a first aspect, the invention features a method of treating infectious diseases in a mammal, comprising administering to a mammalian subject in need thereof a therapeutically effective amount of a compound or prodrug thereof, or pharmaceutically acceptable salt or ester of said compound or prodrug, wherein the compound is an inhibitor of glucose uptake.

Abstract: Provided herein are compounds that modulate glucose uptake activity and are useful for treating cancer, autoimmune diseases, inflammation, infectious diseases, and metabolic diseases. In certain embodiments, the compounds modulate glucose uptake activity by modulating cellular components, including, but not limited to those related to glycolysis and known transporters/co-transporters of glucose such as GLUT1 and other GLUT family members/alternative hexose transporters. In certain embodiments, the compounds have the structure of formula I: Formula (I) wherein the variables have the values disclosed herein.