Omaveloxolone (RTA-408) (RTA-408) is a synthetic triterpenoid that activates the cytoprotective transcription factor Nrf2 and inhibits NF-κB signaling. Phase 2.

Human tumor cell lines:260 nM (GI50), HT-29 cells:1.41 μM (EC50), L929 cells:5.25 μM (EC50), NO:4.4 ± 1.8 nM

Omaveloxolone在 RAW 264.7 细胞中显著提高 Nrf2 靶基因的表达，并逆转了 IFNγ 对 Gclc 表达的抑制。在八种人类肿瘤细胞系的研究中，Omaveloxolone抑制细胞生长，平均 GI50 值为 260 nM，并诱导细胞凋亡。此外，Omaveloxolone还抑制 NF-κB 并激活 JNK，展现其对肿瘤细胞的作用。[1]

在辐射诱发性皮炎的小鼠中，1.0% Omaveloxolone显著减少了表皮和胶原增厚，阻止了真皮坏死，并完全缓解了皮肤溃疡。[2] 在大鼠皮肤中，Omaveloxolone激活 Nrf2 并诱导细胞保护基因的表达。[3] Omaveloxolone也减轻了小鼠的急性放射性造血综合征。[4]

For growth inhibition assays, cells are plated in duplicate 96-well culture dishes at 3 x 103 cells per well. The following day, one plate is treated with RTA 408 and the other is immediately processed for the sulforhodamine B (SRB) assay (time 0). Cells in the RTA 408-treated plate are processed for the SRB assay 72 hours after the start of treatment. Percentage of growth relative to vehicle-treated cells is calculated using: [(Ti-Tz)/(C-Tz)] x 100 where (Tz) is the absorbance value at time zero, (C) is absorbance value from vehicle treated wells after 72 hours, and (Ti) is the absorbance value from wells treated with the drug. Dose-response curves are plotted in GraphPad Prism and GI50 values are calculated(Only for Reference)