BDK inhibitor BT2 is a small molecule allosteric inhibitor of BCKDC kinase (BDK, branched-chain ketoacid dehydrogenase kinase) with IC50 of 3.19 uM.
BDK inhibitor BT2 significantly increases BCKDC activity in wild-type and MSUD cells the mitochondrial branched-chain α-ketoacid dehydrogenase complex (BCKDC).
BDK inhibitor BT2 binds to the same site in BDK as other known allosteric BDK inhibitors, including (S)-α-cholorophenylproprionate ((S)-CPP).
Administration of BT2 at 20 mg/kg/day to wild-type mice for 1 week leads to nearly complete dephosphorylation and maximal activation of BCKDC in heart, muscle, kidneys, and liver with reduction in plasma BCAA concentrations.
BT2 treatment reduced steatosis and/or inflammation, improved sulin sensitivity in HFD-fed and lean mice.
