Figure 1.

Compound A is a nonsecosteroidal VDR ligand. (a) Compound A is a potent agonist in RXR-VDR heterodimerization assay. SaOS-2 cells were cotransfected with expression vectors encoding Gal4-RXRα-LBD and VP16-VDR-LBD along with a Gal4-responsive luciferase reporter. After transfection, cells were treated with vehicle or various concentrations of 1,25-(OH)₂D₃ or compound A, and the reporter activity was expressed as light units ±SE (standard error). A schematic of the RXR-VDR heterodimerization-based ligand-sensing assay and the chemical structures of 1,25-(OH)₂D₃ and compound A are also presented. (b) Compound A is selective for VDR-dependent transactivation. HeLa cells were cotransfected with various nuclear receptor-Gal4 DNA-binding domain chimeras and the reporter pFR-Luc. Cells were treated with 100 nM compound A. Cell extracts were subsequently assayed for luciferase activity. Data are expressed for each receptor as fold induction of luciferase activity relative to vehicle-treated cells and represent the mean of four replicates ± SE.