Parallel strategies for the preparation and selection of liver-targeted glucocorticoid receptor antagonists

Libraries of mifepristone analogs, MP-Acids, were shown to be potent GR antagonists in binding and cell-based functional screens. A high-throughput pharmacokinetic selection strategy was devised to identify MP-Acids with liver-targeting profiles. These conjugates were tested in in vivo models to evaluate liver versus systemic GR antagonism.