ChREBPα/14-3-3 PPI stabilizer 43 is a potent, specific molecular glue as ChREBPα/14-3-3 protein-protein interaction (PPI) stabilizer with EC50 of 3.8 uM, protect human β-cells from glucolipotoxicity.
ChREBPα/14-3-3 PPI stabilizer 43 displays a high selectivity for stabilizing ChREBPα, without affecting any other client peptide up to 100 µM (BRAF, CRAF, p65, USP8, one C-terminal binding motif ERα).
ChREBPα/14-3-3 PPI stabilizer 43 (5 uM, 10 uM) rescues human β-cells from glucolipotoxic death.
ChREBPα/14-3-3 PPI stabilizer 43 stabilizes the ChREBPα/14-3-3 interaction in situ preventing ChREBPα's nuclear translocation in response to glucose or glucose + palmitate, retains ChREBPα in the cytoplasm, preventing its transcriptional activity.
ChREBPα/14-3-3 PPI stabilizer 43 preserves β-cell identity in glucolipotoxicity and prevents upregulation of ChREBPβ in high glucose and glucolipotoxicity.