INTRODUCTION: The development of selective GR agonist and modulators (SEGRAMs) aimed to minimize the adverse effects of chronic glucocorticoid treatment (e.g., hyperglycemia and osteoporosis) by separating the transactivation and transrepression activities of the glucocorticoid receptor (GR). Herein we report the pharmacologic profile of clinical candidate GRM-01, a novel, orally available, non-steroidal SEGRAM. RESULTS: GRM-01 is a potent and selective ligand of human GR versus human PR and MR (inhibition constant = 12 vs. 3,700 and >
10,000 nM, respectively). GRM-01 displayed partial induction (transactivation) at the GR (half-maximal effective concentration [EC CONCLUSION: GRM-01 displays a favorable preclinical pharmacologic profile consistent with a SEGRAM, and based on this is currently in Phase 1 development.