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

In comparison with FADs and LCI699, BI 689648 exhibits remarkable selectivity in vitro, demonstrating an IC50 value of 2.1 nM for CYP11B2 and a selectivity factor of 149 over CYP11B1. Meanwhile, FAD286 presents a comparable IC50 value for CYP11B2 at 2.5 nM, but its higher efficacy against CYP11B1 (94 nM) yields a relatively lower selectivity factor of 38, which is about fourfold lesser than that of BI 689648[1].

After oral administration in cyno monkeys, BI 689648 (5 mg/kg) achieves a peak plasma concentration of ~500 nM. BI 689648 minimally impacts 11-DC, but only at very high plasma concentrations (~10 μM)[1]. For BI 689648 (aldosterone EC50 = 2 nM), significant changes in 11-DOC are observed at plasma concentrations >2000 nM or >1000-fold its aldosterone EC50, whereas FAD286 exhibits a window of ~100-fold.