.Fumarate hydratase is an enzyme of the TCA cycle and cell-permeable inhibitors (1) inhibition of fumarate hydratase can contribute to tumorigenicity in some cells. (2) The use of a photoaffinity labeling strategy identified fumarate hydratase as the principal pharmacological target. Final biochemical studies confirmed dose-dependent, competitive inhibition of this enzyme (3) Chemical inhibition of fumarate hydratase renders cells highly dependent on glucose metabolism for survival.
[1]. Takeuchi T et al. Identification of fumarate hydratase inhibitors with nutrient-dependent cytotoxicity. J Am Chem Soc. 2015 Jan 21;137(2):564-7.