bdk-in-1

BDK-IN-1 (compound (-)-43) is a BDK inhibitor with an IC50 of 0.23 μM and a maximum inhibition rate of 90%. It reduces phosphorylated-E1 levels and is useful in the study of cardiac metabolic diseases.

PF-07208254, a potent BDK inhibitor, enhances cardiometabolic endpoints in mice [1].

PF-07238025, a potent branched-chain ketoacid dehydrogenase kinase (BDK) inhibitor with an EC50 of 19 nM, enhances the stability of the BDK-BCKDH core E2 subunit interaction and inhibits the phosphorylation of the E1 subunit. By modulating BDK, which regulates the phosphorylation of BCKDH, a key enzyme in branched-chain amino acid (BCAA) degradation, PF-07238025 indirectly controls the rate-limiting step in BCAA catabolism. Dysregulated BCAA metabolism is implicated in various cardiometabolic disorders such as heart failure (HF), type 2 diabetes mellitus (T2DM), non-alcoholic fatty liver disease (NAFLD), and obesity. Notably, PF-07238025 has been shown to ameliorate cardiometabolic endpoints and enhance glucose tolerance in mouse models [1].

BT2, a BCKDC kinase (BDK) inhibitor, exhibits an IC50 of 3.19 μM and functions as a potent, selective Mcl-1 inhibitor with a Ki value of 59 μM. Its interaction with BDK induces helix movements in the N-terminal domain, leading to BDK's dissociation from the branched-chain α-ketoacid dehydrogenase complex (BCKDC).

PF-07247685, a potent BCKDC kinase (BDK) inhibitor (EC 50 = 2.2 nM), enhances the binding between BDK and the BCKDH E2 core subunit to block E1 phosphorylation. BDK regulation is crucial for BCKDH activity, which manages the rate-limiting step in the catabolism of branched-chain amino acids (BCAA). Dysfunctional BCAA metabolism is linked to various cardiometabolic disorders such as heart failure (HF), type 2 diabetes mellitus (T2DM), non-alcoholic fatty liver disease (NAFLD), and obesity. PF-07247685 has demonstrated an ability to improve cardiometabolic parameters and glucose tolerance in mice [1].