title: Nonsteroidal antagonists of the mineralocorticoid receptor.
abstract: OBJECTIVE
  The broad clinical use of steroidal mineralocorticoid receptor antagonists (MRAs) is limited by the potential risk of inducing hyperkalemia when given on top of renin-angiotensin system blockade. Drug discovery campaigns have been launched aiming for the identification of nonsteroidal MRAs with an improved safety profile. This review analyses the evidence for the potential of improved safety profiles of nonsteroidal MRAs and the current landscape of clinical trials with nonsteroidal MRAs.
  
  
  RESULTS
  At least three novel nonsteroidal MRAs have reportedly demonstrated an improved therapeutic index (i.e. less risk for hyperkalemia) in comparison to steroidal antagonists in preclinical models. Five pharmaceutical companies have nonsteroidal MRAs in clinical development with a clear focus on the treatment of chronic kidney diseases. No clinical data have been published so far for MT-3995 (Mitsubishi), SC-3150 (Daiichi-Sankyo), LY2623091 (Eli Lilly) and PF-03882845 (Pfizer). In contrast, data from two clinical phase II trials are available for finerenone (Bayer) which demonstrated safety and efficacy in patients with heart failure and additional chronic kidney diseases, and significantly reduced albuminuria in patients with diabetic nephropathy. Neither hyperkalemia nor reductions in kidney function were limiting factors to its use.
  
  
  CONCLUSIONS
  Novel, nonsteroidal MRAs are currently tested in clinical trials. Based on preclinical and first clinical data, these nonsteroidal MRAs might overcome the limitations of today's steroidal antagonists.
authors.affiliation: aGlobal Drug Discovery, Cardiology Research bGlobal Clinical Development, Bayer Healthcare Pharmaceuticals, Wuppertal, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Kolkhof
authors.forename: Christina
authors.initials: C
authors.lastname: Nowack
authors.forename: Frank
authors.initials: F
authors.lastname: Eitner
mesh_terms: D000419:Albuminuria / Q000188:drug therapy*; D000818:Animals; D003928:Diabetic Nephropathies / Q000188:drug therapy*; D006801:Humans; D006947:Hyperkalemia / Q000188:drug therapy*; D000451:Mineralocorticoid Receptor Antagonists / Q000627:therapeutic use*; D018161:Receptors, Mineralocorticoid / Q000378:metabolism*; D012084:Renin-Angiotensin System / Q000187:drug effects
chemical_list: D000451:Mineralocorticoid Receptor Antagonists; D018161:Receptors, Mineralocorticoid