BT2

BT2 is a BCKDC kinase (BDK) inhibitor with an IC50 of 3.19 μM. BT2 (compound 4) is also a potent and selective Mcl-1 inhibitor with a Ki value of 59 μM. BT2 binding to BDK triggers helix movements in the N-terminal domain, resulting in the dissociation of BDK from the branched-chain α-ketoacid dehydrogenase complex (BCKDC) .BT2 treatment reduces the protein levels of BDK in kidneys and heart[1]. The -fold activation of BCKDC activity in the above tissues correlates with decreased phosphorylation in heart, muscle, and kidney after the long term BT2 treatment. BT2 (20 mg/kg/day; intraperitoneal injection; daily; for 7 days; C57BL/6J male mice) treatment robustly enhances BCKDC activity in the heart (12.3-fold) compared with the vehicle-treated animals. Less activation is obtained in muscle and kidney at 3.6- and 3.8-fold, respectively.