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PF-3882845 is a remarkably high affinity selective and orally efficacious mineralocorticoid receptor (MR binding IC50=2.7 nM) antagonist for hypertension and nephropathy. PF-3882845 also binds to progesterone receptor (PR) with the binding IC50 of 310 nM[1].

PF-03882845 is a potent non-steroidal mineralocorticoid antagonist with and IC50 of 0.755 nM, compared to eplerenone with an IC50 of 109 nM. PF-03882845 was tested in a r at model for renal protection against aldosterone-mediated renal disease, and found to be more potent than eplerenone in suppressing the urinary albumin to creatinine ratio (UACR), a measure of renal fibrosis. The therapeutic index, calculated as the ratio of the EC50 for increasing serum K+ to the EC50 for UACR lowering, was 83.8 for PF-03882845 and 1.47 for eplerenone.

[1] Meyers MJ, et al. Discovery of (3S,3aR)-2-(3-chloro-4-cyanophenyl)-3-cyclopentyl-3,3a,4,5-tetrahydro-2H-benzo[g]indazole-7-carboxylic acid (PF-3882845), an orally efficacious mineralocorticoid receptor (MR) antagonist for hypertension and nephropathy. J Med Chem. 2010 Aug 26;53(16):5979-6002. DOI:10.1021/jm100505n