Fig. 3: Fluorination of compounds enhances stabilizing potency.

a Structures and bar graphs of pEC₅₀ values derived from FA compound titrations, for Y = H (blue bars) and Y = F (yellow bars). (For graphs see Supplementary Figs. 7, 8, for EC₅₀ values see Supplementary Table 3) (bars represent mean, n = 2). b, c Titration of 14-3-3β to FITC-labeled ChREBPα peptide (10 nM) against varying fixed concentrations of 30 or 43 (0–500 µM) (mean, n = 2), including the cooperativity factor (α, determined, by fitting, using a thermodynamic equilibrium model²⁷) and intrinsic affinity of the stabilizers to 14-3-3 (K_D^II). d Selectivity studies by titrating 43 to 14-3-3β and eight different 14-3-3 interaction FITC-labeled peptides (all 10 nM) (mean, n = 2). e Crystallographic overlay of 30 (yellow) and 43 (purple) in complex with 14-3-3σ (white cartoon) and ChREBPα (red cartoon). Helix 9 of 14-3-3σ is colored in the same color as the corresponding compound, showing a helical ‘clamping’ effect when 43 (purple) is present. f Surface representation of 43 (purple) in complex with 14-3-3σ (white) and ChREBPα (red), showing the distances (black dashes) of the 43 m-F substitution to the residues (sticks) of 14-3-3σ and ChREBPα. g Interactions of 43 (purple) with 14-3-3σ (white) and ChREBPα (red) (relevant side chains are displayed in stick representation, polar contacts are shown as black dashed lines). Source data are provided as a Source Data file.