Balcinrenone

Balcinrenone (AZD9977) is an orally active mineralocorticoid receptor modulator. Balcinrenone regulates mineralocorticoid receptor activity, inhibits aldosterone-induced target gene expression, and suppresses the activities of renal Toll-like receptor 4, MyD88 and NF-κB. Balcinrenone alleviates renal extracellular matrix remodeling, inflammatory cell infiltration, and the expression of renal injury markers. Balcinrenone restores myocardial perfusion reserve, regulates potassium homeostasis, and induces fecal potassium excretion. Balcinrenone is applicable to research on metabolism-related chronic kidney disease and heart failure^[1][2]. In Vitro:Balcinrenone (0.1-12.5 μM) concentration-dependently inhibits the expression of MR target genes and cardiac injury/inflammatory markers in Aldosterone (HY-113313)-induced H9C2/MR+ rat cardiomyocytes; in the absence of Aldosterone, it partially upregulates Sgk-1^[2] at higher concentrations.
Balcinrenone inhibits aldosterone-induced fibrosis and inflammatory processes in primary human cardiac fibroblasts in a concentration-dependent manner, with complete inhibition of IL-6 at 0.5 μM and complete inhibition of type Ⅰ collagen at 12.5 μM^[2]. In Vivo:Balcinrenone (100 mg/kg; p.o.; once daily; for 8 weeks) inhibits renal extracellular matrix remodeling, inflammatory responses, and TLR4 pathway activation in a mouse model of metabolic chronic kidney disease (CKD), with efficacy comparable to that of Eplerenone (HY-B0251). Meanwhile, it uniquely ameliorates hematological abnormalities induced by CKD and high-fat diet, reduces the ratio of phosphorylated NF-κB to total NF-κB, and decreases the mRNA level of versican^[1].
Balcinrenone (10-100 mg/kg/day; administered via feed mixing; daily dosing; for 24 consecutive weeks) restores myocardial perfusion reserve to the level of healthy mice and attenuates diet-induced perivascular cardiac fibrosis in male C57BL/6J mice with heart failure with preserved ejection fraction (HFpEF)^[2].
Balcinrenone (100 mg/kg; p.o.; twice daily for 4 consecutive days, with an additional single dose on day 5; total 5 days) does not increase plasma potassium levels in male CKD mice subjected to overnight potassium loading stimulation; instead, it enhances fecal potassium excretion^[2].