AZD9977 and eplerenone activities on MR, GR, PR and AR in binding assays. The observed pKi of MR, GR, and PR are 7.5, 5.4 and 4.6, respectively.
Functional interaction of AZD9977 with MR is characterized in a reporter gene assay where the full-length MR drives a luciferase reporter gene in U2-OS cells. AZD9977 antagonizes aldosterone-activated MR with an IC50 of 0.28 μM. Whereas eplerenone is a full antagonist, AZD9977 suppresses only 69% of the MR activity in this assay.
Species selective potencies of AZD9977 are established in reporter gene assays using the MR LBDs from human, mouse or rat. The corresponding IC50 values are 0.37 μM, 0.08 μM and 0.08μM, respectively.