BT2

BT2 is a BCKDC kinase (BDK) inhibitor with an IC₅₀ of 3.19 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)^[1]. BT2 (compound 4) is also a potent and selective Mcl-1 inhibitor with a K_i value of 59 μM^[2]. IC50 & Target:IC50: 3.19 μM (BCKDC kinase)^[1]; Ki: 59 μM (Mcl-1)^[2] In Vivo: 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. 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 treatment reduces the protein levels of BDK in kidneys and heart^[1].