PF-07209326 (Pfizer)

PF-07209326 is an investigational small molecule inhibitor of branched-chain keto acid dehydrogenase kinase (BCKDK) developed by Pfizer for the treatment of heart failure. BCKDK is a mitochondrial protein kinase that negatively regulates the branched-chain keto acid dehydrogenase (BCKD) complex through phosphorylation. The BCKD complex is the rate-limiting enzyme in the oxidative catabolism of branched-chain amino acids (BCAAs) such as leucine, isoleucine, and valine. In patients with heart failure, BCAA catabolism is often impaired, leading to elevated levels of BCAAs and branched-chain keto acids (BCKAs), which are linked to mitochondrial dysfunction, oxidative stress, and impaired cardiac energetics. By inhibiting BCKDK, PF-07209326 restores BCKD complex activity, lowers BCAA/BCKA levels, and potentially improves myocardial metabolism and function. It is currently being evaluated in clinical trials for heart failure with preserved ejection fraction (HFpEF) and heart failure with mildly reduced ejection fraction (HFmrEF).

Other names

BCKDK inhibitor