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].

PF-07247685（0.01-0.3 μM；48小时）在Hek293细胞作用下，通过剂量依赖性途径降低了pBCKDH的水平，同时使BDK的积累提高了50%[1]。

PF-07247685（剂量分别为10 mg/kg、100 mg/kg，每日两次连续给药18天）能显著提高HFD喂养小鼠的葡萄糖耐受性，并减少组织中BCAA/BCKA的浓度[1]。