Discovery and Optimization of Glucose Uptake Inhibitors

Aerobic
glycolysis, originally identified by Warburg as a hallmark
of cancer, has recently been implicated in immune cell activation
and growth. Glucose, the starting material for glycolysis, is transported
through the cellular membrane by a family of glucose transporters
(GLUTs). Therefore, targeting glucose transporters to regulate aerobic
glycolysis is an attractive approach to identify potential therapeutic
agents for cancers and autoimmune diseases. Herein, we describe the
discovery and optimization of a class of potent, orally bioavailable
inhibitors of glucose transporters, targeting both GLUT1 and GLUT3.