BI 689648 is a highly selective inhibitor of aldosterone synthase(CYP11B1 and CYP11B2 with IC50s of 310 and 2.1 nM, respectively).

CYP11B2:2.1 nM, CYP11B1:310 nM

Compare with the FADs and LCI699, BI 689648 is highly selective in vitro, providing an IC50 for CYP11B2 of 2.1 nM and a selectivity factor of 149 over CYP11B1. FAD286, by comparison, shows a similar IC50 for CYP11B2 (2.5 nM). However, its greater potency against CYP11B1 (94 nM) results in a comparatively modest selectivity factor of 38, approximately 4-fold less than BI 689648[1].

After oral administration in cyno monkeys, BI 689648 (5 mg/kg) exhibits a peak plasma concentration of ~500 nM. BI 689648 exhibits minimal impact on 11-DC and only at very high plasma concentrations (~10 μM)[1]. For BI 689648 (aldosterone EC50=2 nM), appreciable changes in 11-DOC are only noted at plasma concentrations >2000 nM or >1000-fold its aldosterone EC50 while FAD286 shows a window of ~100-fold.