Selective aldosterone synthase inhibitors reduce aldosterone formation in vitro and in vivo

Discovery of 4-Aryl-5,6,7,8-tetrahydroisoquinolines as Potent, Selective, and Orally Active Aldosterone Synthase (CYP11B2) Inhibitors: In Vivo Evaluation in Rodents and Cynomolgus Monkeys

“…The recently disclosed isoquinoline compound 3 from Hartmann et al is a non-imidazole-type CYP11B2 inhibitor potent against rat aldosterone synthase but unfortunately not suitable for oral application in rodents ( Figure 1). 16 Herein we report on our aldosterone synthase inhibitor drug discovery program to identify compounds with excellent potency and an improved selectivity profile that are suitable for oral application and would enable the study of biological effects of aldosterone synthase inhibition in both rodents and non-human primates. Figure 1.…”

Inhibition of aldosterone synthase (CYP11B2) by torasemide prevents atrial fibrosis and atrial fibrillation in mice

“…is a non-steroidal compound in order to minimize the risk of side effects caused by interaction with steroid receptors or other steroidogenic enzymes and is the only compound, which is able to inhibit human CYP11B2 to 94% [0.5 µM] and rat CYP11B2 to 65% [2 µM] [34]. Thus, SL242 is a suitable tool for studies in disease-oriented models as described in this paper.…”

“…Therefore we studied the effect of specific inhibition of CYP11B2 by using the novel selective inhibitor SL 242 (for detailed information see compound 7 from To test the effect of selective CYP11B2 inhibition, cardiac fibroblasts were stimulated with angiotensin II (Ang, 1µM; 3 hours) and pre-incubated with or without the CYP11B2 specific inhibitor SL 242 [34]. Ang+SL242 118±23%, p<0.05), whereas MCR activity quantified by MR nuclear translocation and luciferase reporter gene assay was unaffected (Figure 3 A-G).…”

Mineralocorticoid and glucocorticoid receptors in sciatic nerve function and regeneration

“…In this work, a concentration of 10 nM aldosterone was used, above the Kd value ∼0.5 nM for aldosterone binding to MR [20], but in the range of the rat plasma concentration when aldosterone synthesis is stimulated. Plasma concentrations of 0.47-1.04 nM in normal rats [21,22] can reach 4.4-14.4 nM in rats under a low-salt diet [22,23]. The 10 nM aldosterone concentration remains two low to activate GR [20].…”