RO5461111

RO5461111 a highly specific and orally active antagonist of Cathepsin S with IC₅₀s of 0.4 nM (human Cathepsin S) and 0.5 nM (murine Cathepsin S), respectively. RO5461111 can effectively inhibit the activation of antigen-specific T cells and B cells. RO5461111 can improve pulmonary inflammation and lupus nephritis^[1][2]. In Vitro:RO5461111 (16 h) is cytoactive in cell lines of human (RAJI) or mouse (A20), and significantly reduces splenic dendritic cell activation and subsequent expansion and activation of CD4 T cells and CD4/CD8 double negative T cells^[1]. In Vivo:RO5461111 (0.1-100 mg/kg; p.o.; single dose) suppresses T cell priming and antisheep IgG upon vaccination with sheep IgG in BALB/c mice^[1].
RO5461111 (1.31 mg/mouse or 30 mg/kg; p.o.; 8 weeks) disrupts germinal centres (as CXCL12) and reduces hypergammaglobulinemia and lupus autoantibody production F in MRL-Fas(lpr) mice. And RO5461111 reduces lung inflammation and improves lupus nephritis^[1].