Omaveloxolone
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Also known as OmaveloxolonaRTA 408RTA-408SkyclarysOMAVELOXOLONE (RTA-408)
Summary
Omaveloxolone (CHEMBL4303525) is an approved small-molecule anti-inflammatory agent (ATC N07XX25) targeting NFE2L2; indicated across 4 conditions including friedreich ataxia and breast neoplasm.
At a glance
- Status: Approved (max clinical phase 4)
- Modality: Small molecule
- ATC class: N07XX25
- Targets: 1 (NFE2L2)
- Indications: 4 conditions
- Clinical trials: 18
- Chemistry: 554.7 Da · C33H44F2N2O3
Identifiers
Drug identity and classification
| Field | Value |
|---|---|
| ChEMBL ID | CHEMBL4303525 |
| Name | Omaveloxolone |
| Type | Small molecule |
| Max phase | 4 |
| FDA approved | yes |
| PubChem CID | 71811910 |
| ChEBI | CHEBI:229661 |
| ATC | N07XX25 |
| Molecular formula | C33H44F2N2O3 |
| Molecular weight | 554.7 |
| InChIKey | RJCWBNBKOKFWNY-IDPLTSGASA-N |
SMILES: C[C@@]12CC[C@]3(CCC(C[C@H]3[C@H]1C(=O)C=C4[C@]2(CC[C@@H]5[C@@]4(C=C(C(=O)C5(C)C)C#N)C)C)(C)C)NC(=O)C(C)(F)F
IUPAC name: N-[(4aS,6aR,6bS,8aR,12aS,14aR,14bS)-11-cyano-2,2,6a,6b,9,9,12a-heptamethyl-10,14-dioxo-1,3,4,5,6,7,8,8a,14a,14b-decahydropicen-4a-yl]-2,2-difluoropropanamide
ChEBI definition: A semi-synthetic triterpenoid drug. It is an Nrf2 activator that is approved for the treatment of Friedreich’s ataxia in adults and adolescents aged 16 years and older.
Pharmacological roles (ChEBI): antioxidant, anti-inflammatory agent, cardioprotective agent, antineoplastic agent.
Also known as: Omaveloxolona, Omaveloxolone, RTA 408, RTA-408, Skyclarys, OMAVELOXOLONE, OMAVELOXOLONE (RTA-408), Omaveloxolone (RTA-408)
Patent coverage: 187 distinct patent families (527 SureChEMBL compound mentions), from 1 matched compound structure(s). Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.
Targets
Targets
Primary targets (GtoPdb curated mechanism): the Cancer dependency column is the DepMap CRISPR fitness signal (% of screened cell lines dependent on the target).
| Gene | Target | Action | pAffinity | Cancer dependency | UniProt |
|---|---|---|---|---|---|
| NFE2L2 | nuclear factor, erythroid 2 like 2 | Activation | 12.3% | Q16236 |
Bioactivity
No ChEMBL bioactivity rows at pChembl ≥ 5 (expected for biologics / antibodies).
Target pathways
Aggregated over 1 target gene(s): NFE2L2.
Top Reactome pathways
27 total, by targets touching each:
| Pathway | Targets | Genes |
|---|---|---|
| Disease | 1 | NFE2L2 |
| Cellular responses to stress | 1 | NFE2L2 |
| Metabolism of proteins | 1 | NFE2L2 |
| Infectious disease | 1 | NFE2L2 |
| Post-translational protein modification | 1 | NFE2L2 |
| Neddylation | 1 | NFE2L2 |
| Cellular responses to stimuli | 1 | NFE2L2 |
| Potential therapeutics for SARS | 1 | NFE2L2 |
| SARS-CoV Infections | 1 | NFE2L2 |
| Cytoprotection by HMOX1 | 1 | NFE2L2 |
| Regulation of HMOX1 expression and activity | 1 | NFE2L2 |
| Heme signaling | 1 | NFE2L2 |
| Cellular response to chemical stress | 1 | NFE2L2 |
| KEAP1-NFE2L2 pathway | 1 | NFE2L2 |
| Nuclear events mediated by NFE2L2 | 1 | NFE2L2 |
| GSK3B and BTRC:CUL1-mediated-degradation of NFE2L2 | 1 | NFE2L2 |
| NFE2L2 regulating TCA cycle genes | 1 | NFE2L2 |
| NFE2L2 regulating inflammation associated genes | 1 | NFE2L2 |
| NFE2L2 regulating anti-oxidant/detoxification enzymes | 1 | NFE2L2 |
| NFE2L2 regulates pentose phosphate pathway genes | 1 | NFE2L2 |
| NFE2L2 regulating tumorigenic genes | 1 | NFE2L2 |
| NFE2L2 regulating MDR associated enzymes | 1 | NFE2L2 |
| NFE2L2 regulating ER-stress associated genes | 1 | NFE2L2 |
| Regulation of NFE2L2 gene expression | 1 | NFE2L2 |
| Viral Infection Pathways | 1 | NFE2L2 |
| Regulation of PD-L1(CD274) transcription | 1 | NFE2L2 |
| CHD6, CHD7, CHD8, CHD9 subfamily | 1 | NFE2L2 |
Dominant GO biological processes
| GO term | Targets |
|---|---|
| response to ischemia | 1 |
| regulation of transcription by RNA polymerase II | 1 |
| inflammatory response | 1 |
| response to oxidative stress | 1 |
| gene expression | 1 |
| proteasomal ubiquitin-independent protein catabolic process | 1 |
| positive regulation of gene expression | 1 |
| negative regulation of cardiac muscle cell apoptotic process | 1 |
| positive regulation of neuron projection development | 1 |
| protein ubiquitination | 1 |
| positive regulation of blood coagulation | 1 |
| T cell differentiation | 1 |
| endoplasmic reticulum unfolded protein response | 1 |
| cellular response to oxidative stress | 1 |
| PERK-mediated unfolded protein response | 1 |
Indications & clinical
Indications
4 indications (1 at ChEMBL trial phase 4). Phase below is the highest clinical-trial phase recorded for this drug against each disease — not the molecule’s overall approval status (that is in the Summary).
| Indication | Trial phase | MONDO | EFO |
|---|---|---|---|
| Friedreich ataxia | 4 | MONDO:0100339 | MONDO:0100339 |
| breast neoplasm | 2 | MONDO:0021100 | MONDO:0007254 |
| melanoma | 1 | MONDO:0005105 | EFO:0000756 |
| liver disorder | 1 | MONDO:0005154 | EFO:0001421 |
Clinical trials
Total trials: 18.
Phase distribution
| Phase | Trials |
|---|---|
| PHASE1 | 10 |
| Not specified | 4 |
| PHASE2 | 2 |
| PHASE3 | 1 |
| PHASE1/PHASE2 | 1 |
Top trials by phase / activity
| NCT | Phase | Status | Title |
|---|---|---|---|
| NCT06953583 | PHASE3 | RECRUITING | A Study to Learn More About the Effects and Long-Term Safety of BIIB141 (Omaveloxolone) in Participants With Friedreich’s Ataxia Aged 2 to 15 Years Old (BRAVE) |
| NCT02255422 | PHASE2 | COMPLETED | RTA 408 Capsules in Patients With Mitochondrial Myopathy - MOTOR |
| NCT02255435 | PHASE2 | COMPLETED | A Study to Learn About the Effects and Safety of RTA 408 (Omaveloxolone) in People Aged 16 to 40 With Friedreich’s Ataxia |
| NCT02259231 | PHASE1/PHASE2 | COMPLETED | RTA 408 Capsules in Patients With Melanoma - REVEAL |
| NCT06054893 | PHASE1 | ACTIVE_NOT_RECRUITING | A Study to Find Out How BIIB141 (Omaveloxolone) is Processed in the Body and to Learn More About Its Safety in Participants With Friedreich’s Ataxia Aged 2 to 15 Years Old |
| NCT02029729 | PHASE1 | COMPLETED | RTA 408 in the Treatment of Advanced Solid Tumors (NSCLC & Melanoma) - DISCOVER |
| NCT03664453 | PHASE1 | COMPLETED | A Pharmacokinetic Study of Omaveloxolone in Healthy Volunteers |
| NCT04008186 | PHASE1 | COMPLETED | A Clinical Drug-Drug Interaction (DDI) Study With Omaveloxolone |
| NCT05909644 | PHASE1 | COMPLETED | An Open-label DDI Study of Omaveloxolone in Healthy Subjects |
| NCT05927649 | PHASE1 | COMPLETED | A TQTc Study for Omaveloxolone |
| NCT06612879 | PHASE1 | COMPLETED | A Study to Find Out How BIIB141 (Omaveloxolone) Moves From the Blood Into the Breastmilk of Healthy Women Who Are Breastfeeding or Pumping Milk |
| NCT07019064 | PHASE1 | COMPLETED | A Study to Learn How BIIB141 (Omaveloxolone) is Processed in the Body When Taken as Capsules Compared to Sprinkled on Yogurt in Healthy Adults Aged 18 to 55 |
| NCT07149415 | PHASE1 | COMPLETED | A Study to Learn if Taking BIIB141 (Omaveloxolone) Affects How Omeprazole is Processed in the Body and About BIIB141’s Safety in Healthy Adults Aged 18 to 55 |
| NCT07297199 | PHASE1 | COMPLETED | A Study to Learn How the Body Processes BIIB141 (Omaveloxolone) When Taken as a Capsule or as a Tablet Dissolved in Liquid, and to Learn About Its Safety in Healthy Adults Ages 18 to 55 |
| NCT06623890 | Not specified | RECRUITING | A Study to Learn More About the Long-Term Safety of BIIB141 (Omaveloxolone) in Participants With Friedreich’s Ataxia Who Are Prescribed it by Their Own Doctors |
| NCT06628687 | Not specified | RECRUITING | A Study to Learn How BIIB141 (Omaveloxolone) Affects the Health of Participants With Friedrich’s Ataxia Who Took it During Pregnancy and/or During Breastfeeding and About the Health of Their Babies |
| NCT07013292 | Not specified | RECRUITING | Efficacy of Omaveloxolone Treatment for Dysphagia in French Patients With Friedreich’s Ataxia |
| NCT03593499 | Not specified | NO_LONGER_AVAILABLE | Expanded Access to Omaveloxolone for Melanoma for Patients Previously Enrolled in 408-C-1401 |
Clinical evidence (CIViC)
No CIViC predictive evidence (expected for non-precision-medicine drugs).
Pharmacology
Pharmacogenomics
No CPIC/DPWG dosing guideline or drug-level clinical/variant annotations in PharmGKB for this molecule.
Related molecules
Related molecules
Molecules sharing ≥1 of this drug’s curated primary targets, merged from two biobtree sources and ranked by shared-target count, then clinical phase: ChEMBL clinical-stage candidates (development phase ≥2) and PubChem drug-class bioactivity (approved / known drugs acting on the target). Deduplicated by drug name; the drug’s own salt forms are excluded. Note: for a drug with few primary targets a shared-target match can reflect off-target / promiscuous binding rather than the same therapeutic mechanism — the phase ordering surfaces bona-fide therapeutics first.
13 molecules share ≥1 primary target. Top 13 by shared-target count:
| Molecule | Source | Status | Shared targets |
|---|---|---|---|
| DIMETHYL | ChEMBL | Phase 4 (approved) | NFE2L2 |
| DIPYRIDAMOLE | ChEMBL | Phase 4 (approved) | NFE2L2 |
| DOXORUBICIN | ChEMBL | Phase 4 (approved) | NFE2L2 |
| DUTASTERIDE | ChEMBL | Phase 4 (approved) | NFE2L2 |
| KETOCONAZOLE | ChEMBL | Phase 4 (approved) | NFE2L2 |
| TOPOTECAN | ChEMBL | Phase 4 (approved) | NFE2L2 |
| ZAFIRLUKAST | ChEMBL | Phase 4 (approved) | NFE2L2 |
| BARDOXOLONE METHYL | ChEMBL | Phase 3 | NFE2L2 |
| CURCUMIN | ChEMBL | Phase 3 | NFE2L2 |
| RESVERATROL | ChEMBL | Phase 3 | NFE2L2 |
| SULFORAPHANE | ChEMBL | Phase 3 | NFE2L2 |
| HALOFUGINONE | ChEMBL | Phase 2 | NFE2L2 |
| acetylcysteine | PubChem | Approved | NFE2L2 |
Related Atlas pages
- Genes: NFE2L2
- Diseases: Friedreich ataxia
- Drugs: Dipyridamole, Doxorubicin, Dutasteride, Ketoconazole, Topotecan, Zafirlukast, Bardoxolone Methyl, Curcumin, Resveratrol, Sulforaphane, acetylcysteine