Balcinrenone

Balcinrenone (AZD9977) is a potent, selective, and orally active mineralocorticoid receptor (MR) modulator. Balcinrenone is used for heart failure, and chronic kidney disease research^[1]. In Vitro:Balcinrenone (AZD9977) and eplerenone activities on MR, GR, PR and AR in binding assays. The observed pK_i?of MR, GR, and PR are 7.5, 5.4 and 4.6, respectively.
Functional interaction of Balcinrenone with MR is characterized in a reporter gene assay where the full-length MR drives a luciferase reporter gene in U2-OS cells. Balcinrenone antagonizes aldosterone-activated MR with an IC₅₀ of 0.28 μM. Whereas eplerenone is a full antagonist, Balcinrenone suppresses only 69% of the MR activity in this assay.
Species selective potencies of Balcinrenone 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.
In Vivo:Balcinrenone (AZD9977) (oral administration; 10-100 mg/kg; 4 weeks) dose dependently reduces the UACR compared to vehicle in uni-nephrectomised male Sprague Dawley rats administered aldosterone and fed a high-salt diet. Balcinrenone is as efficacious as full MR antagonists on renal protection, despite the partial antagonism observed in?in vitro?assays^[1].
Balcinrenone (oral administration; 100 mg/kg; co-administration with enalapril) stops further disease progression and reduces the urine albumin excretion (UAE) compared to vehicle treatment. Co-administration of enalapril has an apparent additive effect on UAE reduction, although this reduction is not statistically significant^[1].