product name Omaveloxolone (RTA-408)
Description: Omaveloxolone (also known as RTA-408) is a member of the synthetic triterpenoid that activates the cytoprotective transcription factor Nrf2 and inhibits NF-κB signaling. Upon administration, RTA 408 activates the cytoprotective transcription factor Nrf2. In turn, Nrf2 translocates to the nucleus, dimerizes with a small Maf protein (sMaf), and binds to the antioxidant response element (ARE). This induces the expression of a number of cytoprotective genes, including NAD(P)H quinone oxidoreductase 1 (NQO1), sulfiredoxin 1 (Srxn1) etc.
References: PLoS One. 2015 Apr 21;10(4):e0122942; Radiat Res. 2014 May;181(5):512-20.
554.71
Formula
C33H44F2N2O3
CAS No.
1474034-05-3
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 100 mg/mL (180.3 mM)
Water: <1 mg/mL
Ethanol: 20 mg/mL (36.1 mM)
Solubility (In vivo)
10%DMSO+90% Corn oil: 30mg/mL
Synonyms
other peoduct :
| In Vitro |
In vitro activity: RTA 408 potently 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, RTA 408 inhibits growth with an average GI50 value of 260 nM and induces apoptosis. RTA 408 also inhibits NF-κB and activates JNK in tumor cells. Kinase Assay: Cell Assay: 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. |
|---|---|
| In Vivo | In mice with radiation-induced dermatitis, 1.0% RTA 408 markedly reduces epidermal and collagen thickening, prevents dermal necrosis and completely alleviates skin ulcers. In rat skin, RTA 408 activates Nrf2 and induces cytoprotective genes. RTA 408 also mitigates hematopoietic acute radiation syndrome in mice. |
| Animal model | Mice with radiation-induced dermatitis |
| Formulation & Dosage | Dissolved in sesame oil; 1% in 100 μL vehicle (w/v); Topical application |
| References | PLoS One. 2015 Apr 21;10(4):e0122942; Radiat Res. 2014 May;181(5):512-20; Arch Dermatol Res. 2014 Jul;306(5):447-54. |
