| Identification | Back Directory | [Name]
2-Pyrrolidinecarboxamide, N-(1-cyanocyclopropyl)-4-[[4-(2-methyl-4-pyridinyl)-2-(trifluoromethyl)phenyl]sulfonyl]-1-[[1-(trifluoromethyl)cyclopropyl]carbonyl]-, (2S,4R)- | [CAS]
1252637-46-9 | [Synonyms]
RO5461111
2-Pyrrolidinecarboxamide, N-(1-cyanocyclopropyl)-4-[[4-(2-methyl-4-pyridinyl)-2-(trifluoromethyl)phenyl]sulfonyl]-1-[[1-(trifluoromethyl)cyclopropyl]carbonyl]-, (2S,4R)- | [Molecular Formula]
C27H24F6N4O4S | [MOL File]
1252637-46-9.mol | [Molecular Weight]
614.56 |
| Chemical Properties | Back Directory | [Boiling point ]
789.0±60.0 °C(Predicted) | [density ]
1.54±0.1 g/cm3(Predicted) | [form ]
Solid | [pka]
11.51±0.20(Predicted) | [color ]
White to off-white |
| Hazard Information | Back Directory | [Uses]
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 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].
| Animal Model: | Female MRL-Fas(lpr) mice (12-week-old; with proteinuria/serum creatinine levels up)[1] | | Dosage: | 262.5 mg/kg chow; or 5 mg/mouse with 1.31 mg/mouse | | Administration: | Oral gavage; 8 weeks | | Result: | Reduced the activation and expansion of spleen dendritic cells, CD4, double-negative T cells and plasma cells.
Reduced plasma levels of IL-10 and TNF-α. |
| [IC 50]
human Cathepsin S: 0.4 nM (IC50); murine Cathepsin S: 0.5 nM (IC50) | [References]
[1] Rupanagudi KV, et al. Cathepsin S inhibition suppresses systemic lupus erythematosus and lupus nephritis because cathepsin S is essential for MHC class II-mediated CD4 T cell and B cell priming. Ann Rheum Dis. 2015 Feb;74(2):452-63. DOI:10.1136/annrheumdis-2013-203717
[2] Sanchez RA, et al. Preparation of proline dipeptidyl nitrile derivatives as cathepsin, particularly cathepsin S and L, inhibitors: United States, US20100267722. 2010-10-21. |
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