Probing the Complex Binding Modes of the PPARγ Partial Agonist 2‑Chloro‑<i>N</i>‑(3-chloro-4-((5-chlorobenzo[<i>d</i>]thiazol-2-yl)thio)phenyl)-4-(trifluoromethyl)benzenesulfonamide (T2384) to Orthosteric and Allosteric Sites with NMR Spectroscopy Travis S. Hughes Jinsai Shang Richard Brust Ian Mitchelle S. de Vera Jakob Fuhrmann Claudia Ruiz Michael D. Cameron Theodore M. Kamenecka Douglas J. Kojetin 10.1021/acs.jmedchem.6b01340.s002 https://acs.figshare.com/articles/dataset/Probing_the_Complex_Binding_Modes_of_the_PPAR_Partial_Agonist_2_Chloro_i_N_i_3-chloro-4-_5-chlorobenzo_i_d_i_thiazol-2-yl_thio_phenyl_-4-_trifluoromethyl_benzenesulfonamide_T2384_to_Orthosteric_and_Allosteric_Sites_with_NMR_Spectroscopy/4207470 In a previous study, a cocrystal structure of PPARγ bound to 2-chloro-<i>N</i>-(3-chloro-4-((5-chlorobenzo­[<i>d</i>]­thiazol-2-yl)­thio)­phenyl)-4-(trifluoromethyl)­benzenesulfonamide (<b>1</b>, T2384) revealed two orthosteric pocket binding modes attributed to a concentration-dependent biochemical activity profile. However, <b>1</b> also bound an alternate/allosteric site that could alternatively account for the profile. Here, we show ligand aggregation afflicts the activity profile of <b>1</b> in biochemical assays. However, ligand-observed fluorine (<sup>19</sup>F) and protein-observed NMR confirms <b>1</b> binds PPARγ with two orthosteric binding modes and to an allosteric site. 2016-10-26 00:00:00 activity profile PPAR γ site show ligand aggregation orthosteric binding modes orthosteric pocket binding modes -2-yl thiazol Complex Binding Modes NMR chloro