LY 3000328 (Cathepsin S inhibitor) is a selective inhibitor of cathepsin S with IC50 values ​​of 7.7 and 1.67 nM for human and mouse cathepsin S, respectively. LY 3000328 (Cathepsin S inhibitor) may slow or prevent abdominal aortic aneurysm (AAA) expansion and/or reduce the risk of AAA rupture by inhibiting cathepsin S-mediated degradation of extracellular matrix proteins, elastin and collagen.

Cathepsin S (human):7.7 nM, Cathepsin S (mouse):1.67 nM

METHODS: The activity of LY 3000328 (Cathepsin S inhibitor) was evaluated in hCat S and mCat S enzyme inhibition assays.
RESULTS The IC50 values ​​of LY 3000328 (Cathepsin S inhibitor) for inhibiting human and mouse Cat S were 7.7±5.85 and 1.67±1.17 nM, respectively. [1]

METHODS: The efficacy of LY 3000328 (Cathepsin S inhibitor)(1, 3, 10, 30 mg/kg, oral, 28 days) in BID mice was studied.
RESULTS When the lowest dose of LY 3000328 (Cathepsin S inhibitor) was 1 mg/kg, the aortic diameter decreased by 58%, 83% at 3 mg/kg, and 87% at 10 mg/kg; the exposure (AUC) of LY 3000328 (Cathepsin S inhibitor) increased in a dose-dependent manner, indicating good drug disposition performance. [1]