Biochem/physiol Actions
LY3000328 is an orally active, non-covalent, potent and selective cathepsin S (Cat S, Cat-S, CatS, CTSS) inhibitor (human/mouse CatS IC50 = 7.7/1.67 nM) that targets the S2 and S3 subsites without interacting with the active site Cys25. LY3000328 prevents high glucose-induced human aortic smooth muscle cells (SMCs) osteogenic transformation in cultures (1 µM) and displays in vivo therapeutic efficacy in murine models of CaCl2-induced abdominal aortic aneurysm (AAA) (1-10 mg/kg bid po) and CD4+ T cell-mediated colitis induction (0.1 mg/0.2 mL/mouse via daily i.p.).
Orally active, non-covalent, potent and selective cathepsin S (Cat S, Cat-S, CatS, CTSS) inhibitor in vitro and in vivo.