Targeting of Hematologic Malignancies with PTC299, A Novel Potent Inhibitor of Dihydroorotate Dehydrogenase with Favorable Pharmaceutical Properties.

PTC299 was identified as an inhibitor of VEGFA mRNA translation in a phenotypic screen and evaluated in the clinic for treatment of solid tumors. To guide precision cancer treatment, we performed extensive biological characterization of the activity of PTC299 and demonstrated that inhibition of VEGF production and cell proliferation by PTC299 is linked to a decrease in uridine nucleotides by targeting dihydroorotate dehydrogenase (DHODH), a rate-limiting enzyme for pyrimidine nucleotide synthesis. Unlike previously reported DHODH inhibitors that were identified using enzyme assays, PTC299 is a more potent inhibitor of DHODH in isolated mitochondria suggesting that mitochondrial membrane lipid engagement in the DHODH conformation is required for its optimal activity.

The Influence of U.S. Chain Restaurant Food Consumption and Obesity in China and South Korea: An Ecological Perspective of Food Consumption, Self-Efficacy in Weight Management, Willingness to Communicate About Weight/Diet, and Depression.

This study examined the impact of U.S. chain restaurant food consumption in China and South Korea from an ecological perspective.