Fig. 1.

Chemical structures of compounds 1–16, GW501516, and their hPPARδ-targeting activity. (A) Structure of compound 1 highlights scaffold design. Regions that occupy arm I (dark-green lines), core (black lines), and arm II (blue or red lines) in the hPPARδ ligand-binding cavity are highlighted. These sectors are accentuated by color fills: head group (light green), core (gray), fixed unit of the tail (yellow), substituent R₁ (blue), and substituent R₂ (red). (B) Functional groups and associated activities for compounds 1–16 and GW501516. hPPARδ transcriptional responses shown as EC₅₀ values quantified by cell-based luciferase reporter assays. hPPARδ-LBD thermal stabilities shown as both maximal T_m values and EC₅₀ values from fitted dose–response curves (SI Appendix, Fig. S6). ND indicates not determined. (C) Structure of GW501516 with comparable color-coded group designations as in A.