LY3000328

LY3000328 is a potent and selective small molecule inhibitor of cathepsin S (CatS), a cysteine protease implicated in various pathological conditions, including abdominal aortic aneurysm (AAA) and potentially age-related dry eye disease. It exhibits high in vitro potency with IC50 values of 7.7 nM for human CatS and 1.67 nM for mouse CatS, showing excellent selectivity over other cysteine proteases. The compound was developed through structure-based optimization to bind noncovalently to the S2 and S3 subsites of CatS without interacting with the active site Cys25[6][2][3]. In preclinical models, LY3000328 demonstrated efficacy in reducing aortic diameter in AAA models and modulated disease-relevant pathways such as FKN/CX3CR1/p38 MAPK signaling in visceral hypersensitivity models[4][5]. Clinical studies have shown that it is well tolerated at escalating oral doses up to 300 mg, with linear pharmacokinetics[1][8]. The primary mechanism of action is inhibition of cathepsin S activity, which may slow or prevent extracellular matrix degradation associated with AAA progression[1][6].

Other names

Z-FL-COCHO