MLN4924 inhibits NAE and the NF-κB pathway and induces tumor regressions in a primary human DLBCL xenograft model. NOD.SCID mice bearing PHTX22L primary human DLBCL xenografts were administered a single subcutaneous dose of vehicle or MLN4924 at 30 and 60 mg/kg. Tumors were excised at the indicated times, and NEDD8-cullin conjugate levels (A) and relative pIκBα levels (B) were measured in the tumor lysates (20 μg protein per lane) by quantitative immunoblot analysis. (C) Quantitative RT-PCR was performed on RNA extracted from tumor samples using human specific primers to measure levels of NF-κB target gene transcripts. (D) NOD.SCID mice were dosed by subcutaneous administration with either vehicle control or on the doses indicated for 3 cycles of 2 days treatment with 5 days rest. Mean tumor volumes ± SEM are shown (n = 10 mice per group).