Elevated levels of the branched chain α-amino acids valine, leucine, and isoleucine are associated with heart disease and metabolic disorders. The kinase BDK, also known as branched-chain ketoacid deh Show more
Elevated levels of the branched chain α-amino acids valine, leucine, and isoleucine are associated with heart disease and metabolic disorders. The kinase BDK, also known as branched-chain ketoacid dehydrogenase kinase (BCKDK), is a negative regulator of branched-chain α-amino acid metabolism through deactivation of BCKDC, the branched-chain α-ketoacid dehydrogenase complex. Inhibitors of BDK increase the activity of BCKDC and could be useful therapeutic leads for cardiometabolic diseases. We describe a novel bicyclic carboxy amide as an inhibitor of BDK with in vivo activity. Show less
Joseph M Ready · 2021 · Journal of medicinal chemistry · ACS Publications · added 2026-04-24
Inhibitors of cholesteryl ester transfer protein (CETP) elevate HDL levels human clinical trials. However, the first CETP inhibitors proved toxic in pivotal trials or showed minimal therapeutic benefi Show more
Inhibitors of cholesteryl ester transfer protein (CETP) elevate HDL levels human clinical trials. However, the first CETP inhibitors proved toxic in pivotal trials or showed minimal therapeutic benefit. Anacetrapib showed some clinical benefit but is high lipophilic. This Viewpoint highlights efforts to optimize anacetrapib to a best-in-class CETP inhibitor. Show less