Discovery and development of small molecule modulators targeting glutamine metabolism

Cancer cells have been confirmed diverge significantly from normal cells on the metabolic properties. Energy production in cancer cells is abnormally dependent on the glycolysis pathway and other atypical metabolic characteristics such as increased fatty acid synthesis and increased rates of glutamine metabolism. Among these metabolic features of cancers, glutamine metabolism has been reported to be the main energy supply for the growth and viability of a potentially large subset of malignant tumors. In addition, the significance of glutamine metabolism in cancer cells derives from the ability of donate its nitrogen and carbon atoms for the synthesis of important biologically substances. During recent years, emerging evidences have proved the inhibitors targeting glutamine metabolism pathway could be efficient anticancer drugs. Therefore, in this review, we would briefly introduce the regulation of glutamine metabolism, and then summarize the recent advances of small molecule modulators targeting various nodes in glutamine signaling pathway. The current potential obstacles and future therapeutic perspectives in glutamine metabolism are also put forward in order to provide reference for the drug discovery of novel and potent glutamine metabolism modulators. (C) 2018 Elsevier Masson SAS. All rights reserved.