Esaxerenone, a novel nonsteroidal mineralocorticoid receptor blocker (MRB) in hypertension and chronic kidney disease

Abstract

The steroidal mineralocorticoid receptor (MR) antagonists, spironolactone and eplerenone, decrease blood pressure, and attenuate the progression of chronic kidney disease (CKD). However, their use is limited by the fear of inducing hyperkalemia, gynecomastia, impotence, and amenorrhea. Esaxerenone is a novel nonsteroidal MR blocker (MRB) that has been recently developed. In vitro studies have revealed that esaxerenone has a high potency and selectivity for MR compared with spironolactone and eplerenone. Further studies have shown that esaxerenone elicits a strong blood pressure-lowering effect in hypertensive animals. Following the results from phase III clinical trials that esaxerenone is an effective and well-tolerated MRB in Japanese hypertensive patients, esaxerenone became clinically available in Japan from May 2019 for hypertensive patients. Thus, esaxerenone is a promising treatment option for patients with hypertension. In addition, both preclinical studies and phase II clinical trials have shown that esaxerenone elicits renoprotection independent of its antihypertensive effect. Recently, a phase III clinical trial (ESAX-DN study) has also demonstrated the safety and efficacy of esaxerenone in patients with type 2 diabetes and microalbuminuria. These data support future clinical development of esaxerenone for the treatment of renal disease.

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Fig. 1: Co-crystal structure of MR ligand binding domain (MR-LBD) with esaxerenone and eplerenone.

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Acknowledgements

We thank Jodi Smith, Ph.D., from Edanz Group (https://en-author-services.edanzgroup.com/) for editing a draft of this paper.

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Correspondence to Akira Nishiyama.

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AN has received speaking honoraria from Taisho, Tanabe-Mitsubishi, Boehringer Ingelheim, Daiichi-Sankyo, and has received research funds from Daiichi-Sankyo, Boehringer Ingelheim, Bayer and Taisho. The funders had no role in the preparation of this paper. This study was also supported in part by the Salt Sciences Foundation (to AN).

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Wan, N., Rahman, A. & Nishiyama, A. Esaxerenone, a novel nonsteroidal mineralocorticoid receptor blocker (MRB) in hypertension and chronic kidney disease. J Hum Hypertens (2020). https://doi.org/10.1038/s41371-020-0377-6

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