Berotralstat (BCX7353): Structure-guided design of a potent, selective, and oral plasma kallikrein inhibitor to prevent attacks of hereditary angioedema (HAE)

Hereditary angioedema (HAE) is a rare and potentially life-threatening disease that affects an estimated 1 in 50000 individuals worldwide. Until recently, prophylactic HAE treatment options were limited to injectables, a burdensome administration route that has driven the need for an oral treatment. A substantial body of evidence has shown that potent and selective plasma kallikrein inhibitors that block the generation of bradykinin represent a promising approach for the treatment of HAE. Berotralstat (BCX7353, discovered by BioCryst Pharmaceuticals using a structure-guided drug design strategy) is a synthetic plasma kallikrein inhibitor that is potent and highly selective over other structurally related serine proteases. This once-daily, small-molecule drug is the first orally bioavailable prophylactic treatment for HAE attacks, having successfully completed a Phase III clinical trial (meeting its primary end point) and recently receiving the U.S. Food and Drug Administration’s approval for the prophylactic treatment of HAE attacks in patients 12 years and older.

Available from: https://dx.doi.org/10.1021/acs.jmedchem.1c00511