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))
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].
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 CDK toolkit. 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
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.

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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
References
1. EMA. 
EU/3/18/2037: Orphan designation for the treatment of Friedreich’s ataxia.
Accessed on 02/03/2023. Modified on 02/03/2023. ema.europa.eu, https://www.ema.europa.eu/en/medicines/human/orphan-designations/eu-3-18-2037
2. Ghanekar SD, Miller WW, Meyer CJ, Fenelon KJ, Lacdao A, Zesiewicz TA. (2019)
Orphan Drugs In Development For The Treatment Of Friedreich's Ataxia: Focus On Omaveloxolone.
Degener Neurol Neuromuscul Dis, 9: 103-107. [PMID:31686946]
3. Li W, Kong AN. (2009)
Molecular mechanisms of Nrf2-mediated antioxidant response.
Mol Carcinog, 48 (2): 91-104. [PMID:18618599]
4. Lynch DR, Chin MP, Boesch S, Delatycki MB, Giunti P, Goldsberry A, Hoyle JC, Mariotti C, Mathews KD, Nachbauer W et al.. (2023)
Efficacy of Omaveloxolone in Friedreich's Ataxia: Delayed-Start Analysis of the MOXIe Extension.
Mov Disord, 38 (2): 313-320. [PMID:36444905]
5. Lynch DR, Chin MP, Delatycki MB, Subramony SH, Corti M, Hoyle JC, Boesch S, Nachbauer W, Mariotti C, Mathews KD et al.. (2021)
Safety and Efficacy of Omaveloxolone in Friedreich Ataxia (MOXIe Study).
Ann Neurol, 89 (2): 212-225. [PMID:33068037]
6. Profeta V, McIntyre K, Wells M, Park C, Lynch DR. (2023)
Omaveloxolone: an activator of Nrf2 for the treatment of Friedreich ataxia.
Expert Opin Investig Drugs, 32 (1): 5-16. [PMID:36708320]
7. Reisman SA, Gahir SS, Lee CI, Proksch JW, Sakamoto M, Ward KW. (2019)
Pharmacokinetics and pharmacodynamics of the novel Nrf2 activator omaveloxolone in primates.
Drug Des Devel Ther, 13: 1259-1270. [PMID:31118567]
8. Reisman SA, Lee CY, Meyer CJ, Proksch JW, Sonis ST, Ward KW. (2014)
Topical application of the synthetic triterpenoid RTA 408 protects mice from radiation-induced dermatitis.
Radiat Res, 181 (5): 512-20. [PMID:24720753]
9. Reisman SA, Lee CY, Meyer CJ, Proksch JW, Ward KW. (2014)
Topical application of the synthetic triterpenoid RTA 408 activates Nrf2 and induces cytoprotective genes in rat skin.
Arch Dermatol Res, 306 (5): 447-54. [PMID:24362512]