omaveloxolone   Click here for help

GtoPdb Ligand ID: 7573

Synonyms: RTA 408 | RTA-408 | Skyclarys®
Approved drug Immunopharmacology Ligand
omaveloxolone is an approved drug (FDA (2023), EMA (2024))
Compound class: Synthetic organic
Comment: Chemically omaveloxolone (RTA 408) is a second generation synthetic oleanane triterpenoid compound, which structurally resembles bardoxolone, and has difluoropropanamide replacing the carboxylic acid moiety.
This compound is claimed in patent WO2013163344A1. The chemical structure represented above, was drawn from this patent, but structures with alternate stereochemistry are submitted in PubChem.
Pharmacologically omaveloxolone activates the Nrf2 transcription factor, to modulate expression of proteins that have antioxidative, anti-inflammatory, and mitochondrial bioenergetic activities [6-7].

omaveloxolone is commercially available from our sponsors

2D Structure
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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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Physico-chemical Properties
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Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/). All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

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Hydrogen bond acceptors 5
Hydrogen bond donors 1
Rotatable bonds 3
Topological polar surface area 87.03
Molecular weight 554.33
XLogP 6.59
No. Lipinski's rules broken 1

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
SMILES / InChI / InChIKey
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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)

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Canonical SMILES N#CC1=CC2(C)C(C(C1=O)(C)C)CCC1(C2=CC(=O)C2C1(C)CCC1(C2CC(C)(C)CC1)NC(=O)C(F)(F)C)C
Isomeric SMILES N#CC1=C[C@@]2(C)[C@H](C(C1=O)(C)C)CC[C@@]1(C2=CC(=O)[C@H]2[C@@]1(C)CC[C@@]1([C@H]2CC(C)(C)CC1)NC(=O)C(F)(F)C)C
InChI InChI=1S/C33H44F2N2O3/c1-27(2)11-13-33(37-26(40)32(8,34)35)14-12-31(7)24(20(33)17-27)21(38)15-23-29(5)16-19(18-36)25(39)28(3,4)22(29)9-10-30(23,31)6/h15-16,20,22,24H,9-14,17H2,1-8H3,(H,37,40)/t20-,22-,24-,29-,30+,31+,33-/m0/s1
InChI Key RJCWBNBKOKFWNY-IDPLTSGASA-N

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
No information available.
Summary of Clinical Use Click here for help
Omaveloxolone (RTA 408) was investigated for potential to treat a number of conditions, including post-surgical ocular pain/inflammation, dermatological disease eg radiation-induced dermatitis [8] and non-small-cell lung cancer [9]. For a full list of trials registered at ClinicalTrials.gov, click here.
Omaveloxolone was issued with Orphan Drug [2], Fast Track, and Rare Pediatric Disease Designations from the FDA, as a treatment for the ultra-rare, neurodegenerative, and life-limiting disorder Friedreich's ataxia. The EMA also designated omaveloxolone as an orphan drug for this disease [1]. The FDA approved omaveloxolone, as the first therapy for this indication, in February 2023 [6].
Mechanism Of Action and Pharmacodynamic Effects Click here for help
RTA 408 activates the cytoprotective transcription factor Nrf2 (NFE2L2, Q16236) [3] in rat skin and induces expression of cytoprotective genes [9].
Clinical Trials
Clinical Trial ID Title Type Source Comment References
NCT02259231 RTA 408 Capsules in Patients With Melanoma - REVEAL Phase 1/Phase 2 Interventional Reata Pharmaceuticals, Inc.
NCT02255435 RTA 408 Capsules in Patients With Friedreich's Ataxia - MOXIe Phase 2 Interventional Reata Pharmaceuticals, Inc. 4-5