Omaveloxolone (RTA-408)

Catalog No.S7672

Omaveloxolone (RTA-408) Chemical Structure

Molecular Weight(MW): 554.71

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

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Biological Activity

Description Omaveloxolone (RTA-408) is a synthetic triterpenoid that activates the cytoprotective transcription factor Nrf2 and inhibits NF-κB signaling. Phase 2.
Targets
Nrf2 [1]
In vitro

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. [1]

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. [2] In rat skin, RTA 408 activates Nrf2 and induces cytoprotective genes. [3] RTA 408 also mitigates hematopoietic acute radiation syndrome in mice. [4]

Protocol

Cell Research:[1]
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  • Cell lines: A375, NCI-H460, A2058, MDA-Mb-231, HCT116, 786-0, A549, and PANC-1 cells
  • Concentrations: ~1 μM
  • Incubation Time: 72 hours
  • Method: 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)
Animal Research:[2]
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  • Animal Models: Mice with radiation-induced dermatitis
  • Formulation: sesame oil
  • Dosages: 1% in 100 μL vehicle (w/v)
  • Administration: Topical application
    (Only for Reference)

Solubility (25°C)

In vitro DMSO 100 mg/mL (180.27 mM)
Ethanol 20 mg/mL (36.05 mM)
Water Insoluble
In vivo Add solvents to the product individually and in order(Data is from Selleck tests instead of citations):
10%DMSO+90% Corn oil
For best results, use promptly after mixing.
30mg/mL

* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Chemical Information

Molecular Weight 554.71
Formula

C33H44F2N2O3

CAS No. 1474034-05-3
Storage powder
in solvent
Synonyms N/A

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Clinical Trial Information

NCT Number Recruitment interventions Conditions Sponsor/Collaborators Start Date Phases
NCT03902002 Recruiting Drug: Omaveloxolone 50 mg capsules Hepatic Impairment Reata Pharmaceuticals Inc. July 19 2019 Phase 1
NCT03931590 Recruiting Drug: [14C]-Omaveloxolone Healthy Male Subjects Reata Pharmaceuticals Inc. April 11 2019 Phase 1
NCT03664453 Completed Drug: omaveloxolone Healthy Reata Pharmaceuticals Inc. October 29 2018 Phase 1
NCT02029716 Completed Drug: RTA 408 Lotion 0.5% 1% 3%|Drug: Lotion vehicle/placebo Healthy Reata Pharmaceuticals Inc.|AbbVie December 2013 Phase 1

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Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

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NF-κB Signaling Pathway Map

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID