Synthetic inhibitors of human tissue kallikrein.
We have developed a series of novel, potent low molecular weight (4-600 Da) inhibitors of TK which were stable to cleavage by the enzyme and showed a high degree of selectivity for TK over several other serine proteases. Compound 7 (CH-2856) was found to reduce eosinophilia in a model of allergic inflammation. The effects observed in vivo provide further evidence for the involvement of TK and kinins in the pathophysiology of allergic diseases such as asthma.
Evans
D M
DM
Ferring Research Institute, University of Southampton Research Centre, UK.
Jones
D M
DM
Pitt
G R
GR
Ashworth
D
D
De Clerck
F
F
Verheyen
F
F
Szelke
M
M
D000596:Amino Acids / Q000032:analysis; D000818:Animals; D006168:Guinea Pigs; D006801:Humans; D007610:Kallikreins / Q000037:antagonists & inhibitors*; D011480:Protease Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D020840:Tissue Kallikreins
D000596:Amino Acids; D011480:Protease Inhibitors; D007610:Kallikreins; D020840:Tissue Kallikreins