Sebetralstat CAS# 1933514-13-6

Sebetralstat is a highly potent and selective oral small-molecule inhibitor of plasma kallikrein (PKa), with a Ki of ~3.0 nM and an isolated human PKa IC₅₀ of ~6.0 nM. In human whole plasma stimulated with dextran sulfate (to mimic activation of the kallikrein–kinin system, KKS), sebetralstat achieved an IC₅₀ of ~54.4 nM in healthy donor plasma and ~47.5 nM in HAE-patient plasma; and in those assays it protected high‐molecular‐weight kininogen (HK) from cleavage with an IC₅₀ ~200 nM. The compound demonstrates >1,500-fold selectivity over a range of related serine proteases (FXIIa, FXIa, FXa, etc.). In pharmacodynamic studies in healthy volunteers, a 600 mg single oral dose gave >90% inhibition of DXS-stimulated plasma PKa activity at ~20 min post-dose and maintained high inhibition (~89%) through ~6 h, and >60% for up to ~10 h.