Using a human cathepsin K-targeting inhibitor screen, a new leupeptin analogue, leupeptazin (1), containing an unprecedented piperidinotriazine moiety, was isolated from a liquid culture of soil Streptomyces sp. 1S2-4 collected in northern Italy. The structure of leupeptazin was established using HRESIMS as well as ID and 2D NMR data. The inhibitory activity of the compound towards the collagenase cathepsin K was tested in vitro to reveal moderate activity with an inhibition constant, K-i of 44 mu M. (C) 2017 Elsevier Ltd. All rights reserved.