PF-07208254

PF-07208254 is a selective, orally active allosteric inhibitor of branched-chain ketoacid dehydrogenase kinase (BDK) (IC50=110 nM, Ki=54 nM, KD=84 nM) . PF-07208254 inhibits BDK-mediated BCKDH phosphorylation and enhances the catabolism of branched-chain amino acids (BCAAs) and branched-chain keto acids (BCKAs) by binding to the allosteric pocket of BDK, reducing BDK binding to BCKDH-E2 and promoting BDK degradation. PF-07208254 inhibits BDK activity in human skeletal muscle cells (IC50=540 nM) and has activity to improve cardiac function and metabolism. PF-07208254 can be used in the study of cardiometabolic diseases (e.g., heart failure, type 2 diabetes) [1][2].

Product Specifications

CAS Number

[2573122-40-2]

UNSPSC

12352005

Target

PDHK

Type

Reference compound

Related Pathways

Metabolic Enzyme/Protease

Applications

Neuroscience-Neuromodulation

Field of Research

Metabolic Disease; Cardiovascular Disease

Assay Protocol

https://www.medchemexpress.com/pf-07208254.html

Purity

99.69

Solubility

DMSO : 100 mg/mL (ultrasonic)

Smiles

FC1=CC(SC(C(O)=O)=C2Cl)=C2S1

Molecular Formula

C7H2ClFO2S2

Molecular Weight

236.67

References & Citations

[1]Roth Flach RJ, et al. Small molecule branched-chain ketoacid dehydrogenase kinase (BDK) inhibitors with opposing effects on BDK protein levels. Nat Commun. 2023 Aug 9;14 (1) :4812.|[2]Filipski KJ, et al. Discovery of First Branched-Chain Ketoacid Dehydrogenase Kinase (BDK) Inhibitor Clinical Candidate PF-07328948. J Med Chem. 2025 Feb 13;68 (3) :2466-2482.