1,2,4-Triazole derivatives as transient inactivators of kallikreins involved in skin diseases

We describe here 1,2,4-triazoles derivatives identified as transient inactivators acting at the nanomolar level on human kallikreins (hK5, hK7 and hK14) and matriptase. Both the nature of the targeted enzymes and structural variations of the inhibitors influence the life-times of acyl-enzymes. These nonpeptidic, transient and low-molecular-weight inhibitors were found to be noncytotoxic against healthy human keratinocytes. These molecules may be useful to counteract dysregulated proteolytic cascades observed in dermatological disorders such as Netherton syndrome. (C) 2013 Elsevier Ltd. All rights reserved.