“…In this context, current efforts are specifically directed to design new suitable cathepsin K inhibitors which could be devoid of these potential side effects (Black and Percival, 2006;Desmarais et al, 2008;Le Gall et al, 2008;Brömme and Lecaille, 2009). Most of the cathepsin L targeted agents which have been developed are a series of different classes of antagonists including small molecule inhibitors with a higher selectivity for cathepsin L (Katunuma et al, 2002a,b;Marquis et al, 2005;Sadaghiani et al, 2007;Myers et al, 2008;Palermo and Joyce, 2008;Yadav et al, 2008;Asaad et al, 2009;Bethel et al, 2009;Long and Chagnovich, 2009;Rebbaa et al, 2009;Kishore Kumar et al, 2010), alternative forms of endogenous inhibitors (Brand et al, 2004;Gianotti et al, 2008), antibodies and antisense oligonucleotides (Krueger et al, 2001;Rousselet et al, 2004;Frade et al, 2008;Long and Chagnovich, 2009) or natural products (Lion et al, 2009;Ogawa et al, 2009). Preclinical studies showed that some of these molecules were effective to inhibit, in vitro, bone matrix digestion at the level of resorption lacuna and to promote bone mineralization, whereas, in vivo, these agents were able to suppress RANKL or M-CSF or TNF-a stimulated bone pit formation and to protect tumor bearing mice from malignant hypercalcemia and to decrease bone metastasis formation (Hill et al, 1994;Katunuma et al, 2002a,b;Brand et al, 2004;Long and Cha-gnovich, 2009).…”