Figure 1. Z compounds selectively activate Gal4-DBD-RXRα-LBD transcriptional activity.

(A) The chemical structures of Z-1 ((E)-1-methyl-4-(2-nitrovinyl)benzene), Z-10 ((E)-1-(2-nitrovinyl)naphthalene), Z-11 ((E)-2-(2-nitrovinyl)naphthalene) and Z-12 ((E)-9-(2-nitrovinyl)anthracene). (B) Z-1 selectively activates RXRα transcriptional activity. HEK293T cells transfected with the indicated pBIND-plasmids and pG5-luc were treated with 9-cis-RA (0.1 µM), PPT (10 µM) and Z-1 (10 µM) for 12 h. For all luciferase activity assays, renilla luciferase values were normalized to firefly luciferase activity and plotted as relative luciferase activity. (C) Z-10 and Z-12 are optimized Z-1 derivatives. HEK293T cells transfected with pBIND-RXRα-LBD and pG5-luc were treated with 9-cis-RA (0.1 µM) and the indicated Z-1 derivatives (10 µM). Luciferase activities were measured 12 h post treatment and relative luciferase activity was plotted. (D) Z-10 and Z-12 selectively activate RXRα transcriptional activity. HEK293T cells transfected with the indicated pBIND-plasmids and pG5-luc were treated with 9-cis-RA (0.1 µM), ATRA (0.1 µM), PPT (10 µM), Dex (1 µM), T09 (1 µM), Ros (1 µM), Z-10 (5 µM) and Z-12 (5 µM) for 12 h, and luciferase activities were measured and normalized. Data shown are representative of at least three independent experiments. 9-cis-RA, 9-cis-retinoic acid; ATRA, all-trans retinoic acid; PPT, propyl pyrazole triol; Dex, Dexamethasone, T09, T0901317; Ros, Rosiglitazone; RXRα, retinoid X receptor α; RARα and RARγ, retinoic acid receptor α and γ, respectively; ERα, estrogen receptor α; GR, glucocorticoid receptor; LXRα, liver X receptor α; PPARγ, peroxisome proliferator-activated receptor γ.