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

Omaveloxolonepotently increases expression of Nrf2 target genes and reverses IFNγ-mediated suppression of Gclc expression in RAW 264.7 cells. In a panel of eight human tumor cell lines, Omaveloxoloneinhibits growth with an average GI50 value of 260 nM and induces apoptosis. Omaveloxolonealso inhibits NF-κB and activates JNK in tumor cells. [1]

In mice with radiation-induced dermatitis, 1.0% Omaveloxolonemarkedly reduces epidermal and collagen thickening, prevents dermal necrosis and completely alleviates skin ulcers. [2] In rat skin, Omaveloxoloneactivates Nrf2 and induces cytoprotective genes. [3] Omaveloxolonealso mitigates hematopoietic acute radiation syndrome in mice. [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)