Discovery of Cell-Permeable Allosteric Inhibitors of Liver Pyruvate Kinase: Design and Synthesis of Sulfone-Based Urolithins.

ABSTRACT: Metabolic dysfunction-associated fatty liver disease (MAFLD) presents a significant global health challenge, characterized by the accumulation of liver fat and impacting a considerable portion of the worldwide population. Despite its widespread occurrence, effective treatments for MAFLD are limited. The liver-specific isoform of pyruvate kinase (PKL) has been identified as a promising target for developing MAFLD therapies. Urolithin C, an allosteric inhibitor of PKL, has shown potential in preliminary studies. Expanding upon this groundwork, our study delved into delineating the structure-activity relationship of urolithin C via the synthesis of sulfone-based urolithin analogs. Our results highlight that incorporating a sulfone moiety leads to substantial PKL inhibition, with additional ca

SUBMITTER: Iqbal S 

PROVIDER: S-EPMC11277446 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature