A Simple, Sensitive and Selective Fluorogenic Assay to Monitor Kallikrein Activity in Activated Plasma

Safety, pharmacokinetics, and pharmacodynamics of avoralstat, an oral plasma kallikrein inhibitor: phase 1 study

“…Plasma kallikrein activity was measured with a contact activation assay that used ellagic acid as the activator and a fluorogenic artificial substrate specific for plasma kallikrein . On‐treatment results are expressed as percent inhibition compared to baseline enzyme activity and reflect inhibition additional to the activity of normal levels of relevant plasma components (C1INH and α‐2 macroglobulin) in healthy subjects.…”

“…The synthetic small‐molecule avoralstat (RN: 918407‐35‐9) is a potent inhibitor of plasma kallikrein that suppresses HK/kallikrein‐dependent bradykinin production on human endothelial cells . The effect of avoralstat on kallikrein activity in human plasma has been demonstrated using a novel assay developed by the authors , in which contact activation is stimulated by ellagic acid and enzyme activity is measured with a specific fluorogenic substrate. In an ex vivo study of plasma samples from 51 healthy human subjects, the EC 50 values for avoralstat in this assay were 1.14 nM to 11.1 nM .…”

Detecting oral kallikrein-targeting therapy through triggered contact activation: A phase I study

“…3 Similar approaches have been used to demonstrate the biologic activity of other HAE therapies. [4][5][6] However, the level to which PKa needs to be inhibited to effectively protect HK remains uncertain. We recently developed an ELISA-based assay to detect cHK in plasma of patients with HAE.…”