| In Vivo: |
MX1013 is an effective antiapoptotic agent in vivo. MX1013 not only inhibits local tissue apoptosis, but also can protect animals against its lethal effects[1]. Animal Model: Female ND4 Swiss Webster mice (16.5-21 g)[1] Dosage: 0, 0.25, 1, 10 mg/kg (formulated in an aqueous vehicle containing 50 mm Tris-HCl, pH 8.0) Administration: Injected i.v. Result: The lowest dose of 0.25 mg/kg protected 66% of the mice from the lethal effects of anti-Fas antibody at the 3 h time point, and 1 and 10 mg/kg dose protected 100% of the mice at the 3 h time point. |
| In Vitro: |
MX1013 inhibits caspases 1, 3, 6, 7, 8, and 9, with IC50 values ranging from 5 to 20 nm. MX1013 is selective for caspases, and is a poor inhibitor of noncaspase proteases, such as cathepsin B, calpain I, or Factor Xa (IC50 values >10 μm)[1]. MX1013 inhibits three key markers of apoptosis: the proteolytic maturation of caspase 3, the caspase-mediated cleavage of PARP, and the fragmentation of genomic DNA[1]. Cell Proliferation Assay[1] Cell Line: Jurkat T-lymphocytes Concentration: 0, 0.05, 0.1, 0.25, 0.5 μM Incubation Time: Preincubated for 2 h Result: Neither caspase 3 processing nor PARP cleavage could be detected at 0.5 μM. At concentrations of 0.05 μM, caspase 3 processing and PARP cleavage were still markedly reduced. |
