Figure 1: Structure activity relationship around enantiomers SR1663 and SR1664.
From: Pharmacological repression of PPARγ promotes osteogenesis
(a) Chemical structures of SR1664 and R-enantiomer SR1663. (b) Transcriptional activity of a PPARγ-Gal4:UAS-Luciferase promoter–reporter assay in HEK293T cells with 1 μM ligand. (c) Alignment of PPARγ:SR1663 (blue) and PPARγ:SR1664 (green) co-crystal structures. Zoomed panel highlights stereo-specific interaction with residue F282. (d) HDX buildup curves of PPARγ LBD helix 3 peptide (IRI F QGCQ) containing F282 in the presence of SR1663 and SR1664. (e) Extracted one-dimensional plots from two-dimensional [1H,15N]-TROSY-HSQC NMR data for PPARγ LBD in the presence of SR1663 or SR1664; half-height resonance line widths are indicated. (f) Transcriptional activity of wild type versus F282A PPARγ in PPARγ:PPRE-Luciferase promoter–reporter assay with 1 μM SR1664 in HEK293T cells. (g) Wild type versus F282A PPARγ:NCoR NR Box 1 peptide affinity with 1 μM SR1664 in TR-FRET assay. Error bars, s.e.m; one-way analysis of variance, Dunnett’s post hoc test *P<0.05, **P<0.01, ***P<0.001.
