ChREBPα/14-3-3 regulator-1

ChREBPα/14-3-3 regulator-1 (compound 43) is a selective and potent molecular glue stabilizer of ChREBPα/14-3-3 protein-protein interaction in cell-free biochemical assays, with an EC₅₀ of 3.8 μM, a cooperator factor of 72, and a K_DII of 162 μM for 14-3-3β^[1].
ChREBPα/14-3-3 regulator-1 (100 μM) stabilizes the interaction between ChREBPα and all 7 14-3-3 isoforms, with stabilization folds ranging from 12 to 93. Among these, it exhibits the highest stabilization fold of 93 for 14-3-3ζ^[1].
ChREBPα/14-3-3 regulator-1 (up to 100 μM) selectively stabilizes the ChREBPα/14-3-3 PPI, while failing to stabilize the PPIs of other tested 14-3-3 client proteins including BRAF, CRAF, p65, USP8, ERα, Pin1 and ExoS; its ChREBPα PPI selectivity is maintained across different 14-3-3 isoforms^[1].
ChREBPα/14-3-3 regulator-1 (5 and 10 μM; 48 h) significantly reduces cell death of INS-1 β-cell-like cells under glucolipotoxic conditions induced by 20 mM D-Glucose (HY-B0389) plus 500 μM Palmitic acid (HY-N0830), and exhibits no obvious cytotoxicity on its own^[1]
ChREBPα/14-3-3 regulator-1 (10 μM; 20 mM D-Glucose + 500 μM Palmitic acid; up to 72 h) significantly reduces glucolipotoxicity-induced death of primary human pancreatic islet β cells, while it does not cause a significant increase in β cell count within the 72 h observation period^[1].
ChREBPα/14-3-3 regulator-1 (10 μM; 24 h) reduces TUNEL-positive signals in human primary islet cells under the condition of 20 mM D-Glucose + 500 μM Palmitic acid, which further supports its role in reducing glucolipotoxicity-induced cell death^[1].
The protective effect of ChREBPα/14-3-3 regulator-1 (10 μM; 24 h) on human pancreatic islet β cells depends on the inhibition of ChREBPβ induction; silencing of ChREBPβ mimics its protective effect, whereas ChREBPα/14-3-3 regulator-1 fails to prevent the increase in β cell death when ChREBPβ is overexpressed^[1].
ChREBPα/14-3-3 regulator-1 binds to the composite PPI interface within the ChREBPα/14-3-3σ ternary complex and induces a conformational "clamping" effect of helix 9 of 14-3-3σ, thereby enhancing the ChREBPα/14-3-3 interaction; the PDB ID of this crystal structure is 8BWE^[1].
ChREBPα/14-3-3 regulator-1 maintains the ChREBPα/14-3-3 interaction in INS-1 cells under high-glucose conditions, and blocks the transient nuclear translocation of ChREBPα induced by high glucose or glucolipotoxicity; it also inhibits the accumulation of nuclear ChREBPβ in CRISPR/Cas9-engineered INS-1 cells^[1].
ChREBPα/14-3-3 regulator-1 (10 μM; 24 h) inhibits high glucose- and glucolipotoxicity-induced upregulation of ChREBPβ mRNA in human primary islets, maintains INS and PDX1 mRNA expression under glucolipotoxic conditions, and suppresses glucose-induced TXNIP promoter activity in INS-1 cells^[1].
ChREBPα/14-3-3 regulator-1 (10 μM; 24 h) does not significantly alter the expression of other 14-3-3 client protein-related genes, including USP8, RELA, PIN1, NFATC1 and BRAF, in human islets; it reduces the expression of β-cell dedifferentiation marker ALDH1A3 under low-glucose conditions, but this effect is not obvious under high-glucose or glucolipotoxic conditions^[1].
Preincubation with ChREBPα/14-3-3 regulator-1 for 24 h increases the glucose-stimulated insulin secretion (GSIS) stimulation index of human primary islets under high-glucose conditions, without affecting the KCl stimulation index or total insulin content^[1].
ChREBPα/14-3-3 regulator-1 (10 μM) does not affect high glucose-induced dissociation of 14-3-3/NFATC1, which supports its intracellular selectivity for ChREBPα/14-3-3 PPI^[1].
ChREBPα/14-3-3 regulator-1 (10 μM) does not affect glucose-stimulated Ca²⁺ influx in INS-1 cells, but enhances active mitochondrial signals and the ATP/ADP ratio under high-glucose conditions^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.