To optimize the oxaprozin scaffold for selective inverse Nurr1 agonism with no remaining activity on RXR, we have systematically studied its SAR for both transcription factors with analogues 7-60 and additionally considered SAR knowledge on structurally related RXR agonists from previous studies . Nurr1 and RXRα modulation by 6-60 were determined in uniform Gal4-hybrid reporter gene assays using the respective chimeric receptor to control a Gal4-responsive firefly luciferase as reporter gene. Constitutively expressed renilla luciferase (SV40 promoter) served to monitor transfection efficiency and test compound toxicity.