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- W235787585 abstract "Abstract Since therapeutic blockade of the cellular proteasome has previously demonstrated preclinical efficacy against inflammatory diseases, the evaluation of a novel, orally active proteosome inhibitor, CEP-18770, was tested in models of systemic lupus erythematosus (SLE). Age matched, 8-week old (MRL/lpr) or 8 months old (NZM) mice with established SLE or lupus nephritis (LN), respectively, were treated with CEP-18770 either 3mg/kg 1-2x/wk, iv, or orally at 10mg/kg. Reference agent, bortezomib, was provided at 0.5mg/kg, 1x/wk, or 0.3mg/kg 1-2x/wk. Standard of care agents included dexamethasone or cyclophosphamide. Mice were monitored for clinical, pathological and immunological changes. Reductions in the frequencies of specific anti-chromatin, smith and dsDNA antibody secreting cells (ASC) and levels of the corresponding antinuclear antibodies (ANA), followed CEP-18770 treatment and were accompanied by decreases in spleen ASCs, plasma cells, and serum cytokines (IL-12, IL-17A, IL-1β, TNFα). CEP-18770-treatment also mitigated the incidence of renal histopathology, and subsequently, proteinuria, in both models. CEP-18770 treatment also extended survival for both models over bortezomib. Proteasome inhibition and IκBα accumulation in target tissues followed administration of CEP-18770 and bortezomib. CEP-18770 was equivalent to treatment with bortezomib; however, CEP-18770 resulted in greater tolerability and rate of response resulting in greater SLE disease stability overtime." @default.
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- W235787585 date "2011-04-01" @default.
- W235787585 modified "2023-09-27" @default.
- W235787585 title "Novel, orally active proteasome inhibitor, CEP-18770, protects and treats disease in preclinical mouse models of lupus nephritis (164.3)" @default.
- W235787585 doi "https://doi.org/10.4049/jimmunol.186.supp.164.3" @default.
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