Targeting the sugar metabolism of tumors with a first-in-class 6-phosphofructo-2-kinase (PFKFB4) inhibitor.
Louisville, United States. In Oncotarget, Aug 2015
Recent studies have demonstrated that cancer cells from several tissue origins and genetic backgrounds require the expression of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 4 (PFKFB4), a regulatory enzyme that synthesizes an allosteric activator of glycolysis, fructose-2,6-bisphosphate. We report the discovery of a first-in-class PFKFB4 inhibitor, 5-(n-(8-methoxy-4-quinolyl)amino)pentyl nitrate (5MPN), using structure-based virtual computational screening.
Endothelial Metabolism Driving Angiogenesis: Emerging Concepts and Principles.
Leuven, Belgium. In Cancer J, Jul 2015
During vessel sprouting, the glycolytic activator PFKFB3 (6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase-3) promotes vessel branching by rendering ECs more competitive to reach the tip of the vessel sprout, whereas fatty acid oxidation selectively regulates proliferation of endothelial stalk cells.
p53- and p73-independent activation of TIGAR expression in vivo.
Glasgow, United Kingdom. In Cell Death Dis, 2014
TIGAR (TP53-induced glycolysis and apoptosis regulator) functions as a fructose-2,6-bisphosphatase and its expression results in a dampening of the glycolytic pathway, while increasing antioxidant capacity by increasing NADPH and GSH levels.