asp1617

ASP1617 is a novel, potent, and highly specific small molecule inhibitor of cathepsin S (CatS), developed by Astellas Pharma. Cathepsin S is a key protease involved in antigen peptide loading onto lysosomal/endosomal MHC class II molecules through invariant chain degradation, which promotes antigen presentation. By inhibiting CatS, ASP1617 suppresses antigen presentation via MHC class II pathways, leading to reduced T and B cell activation and decreased antibody production from B cells. Preclinical studies have shown that ASP1617 induces accumulation of the invariant chain and decreases surface expression of MHC class II on both mouse and human B cells. In animal models of systemic lupus erythematosus (SLE), oral administration of ASP1617 suppressed anti-dsDNA IgG levels, prevented progression of lupus-like glomerulonephritis, and significantly reduced proteinuria excretion. The drug has completed Phase 1 clinical trials in healthy volunteers.