Meshach Pillai, Pascale Lafortune, Abdoulaye Dabo, Howard Yu, Sangmi S Park, Harsha Taluru, Huma Ahmed, Dylan Bobrow, Zeeshan Sattar, Bakr Jundi, Joshua Reece, Romy Rodriguez Ortega, Brian Soto, Selome Yewedalsew, Robert Foronjy, Anne Wyman, Patrick Geraghty, Michael Ohlmeyer
The activity of protein phosphatase 2A (PP2A), a serine-threonine phosphatase, is reduced in the lung fibroblasts of idiopathic pulmonary fibrosis (IPF) patients. The objective of this study was to determine whether the reactivation of PP2A could reduce fibrosis and preserve the pulmonary function in a bleomycin (BLM) mouse model. Here, we present a new class of direct small-molecule PP2A activators, diarylmethyl-pyran-sulfonamide, exemplified by ATUX-1215. ATUX-1215 has improved metabolic stability and bioavailability compared to our previously described PP2A activators...
November 10, 2023: ACS Pharmacology & Translational Science