1. Academic Validation
  2. Selective inhibition of human mast cell tryptase by gabexate mesylate, an antiproteinase drug

Selective inhibition of human mast cell tryptase by gabexate mesylate, an antiproteinase drug

  • Biochem Pharmacol. 2001 Feb 1;61(3):271-6. doi: 10.1016/s0006-2952(00)00550-5.
F Erba 1 L Fiorucci S Pascarella E Menegatti P Ascenzi F Ascoli
Affiliations

Affiliation

  • 1 Department of Experimental Medicine and Biochemical Sciences, University of Rome 'Tor Vergata', Via di Tor Vergata 135, I-00133, Rome, Italy. [email protected]
Abstract

Gabexate mesylate is a non-antigenic synthetic inhibitor of trypsin-like serine proteinases that is therapeutically used in the treatment of pancreatitis and disseminated intravascular coagulation and as a regional anticoagulant for hemodialysis. Considering the structural similarity between gabexate mesylate and arginine-based inhibitors of trypsin-like serine proteinases, the effect of gabexate mesylate on human and bovine mast cell tryptase action was investigated. Values of the inhibition constant (K(i)) for gabexate mesylate binding to human and bovine tryptase were 3.4 x 10(-9) M and 1.8 x 10(-7) M (at pH 7.4 and 37.0 degrees ), respectively. Furthermore, gabexate mesylate inhibited the fibrinogenolytic activity of human tryptase. On the basis of the available x-ray crystal structure of human tryptase, the possible binding mode of gabexate mesylate to human and bovine tryptase was analyzed. Human tryptase inhibition by gabexate mesylate may account for the reported prevention of inflammation, erosion, and ulceration of skin and mucosae.

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