OMAVELOXOLONE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C33H44F2N2O3
Molecular Weight	554.7109
Optical Activity	UNSPECIFIED
Defined Stereocenters	7 / 7
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[H][C@@]12CC(C)(C)CC[C@@]1(CC[C@]3(C)[C@]2([H])C(=O)C=C4[C@@]5(C)C=C(C#N)C(=O)C(C)(C)[C@]5([H])CC[C@@]34C)NC(=O)C(C)(F)F

InChI

InChIKey=RJCWBNBKOKFWNY-IDPLTSGASA-N

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

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/25897966 | http://adisinsight.springer.com/drugs/800039652 | https://reatapharma.com/

Omaveloxolone (RTA-408) is a synthetic triterpenoid exerting antioxidant inflammation modulator properties. It activates the transcription factor Nrf2 and inhibits NF-κB signaling. Omaveloxolone demonstrated antioxidant, anti-inflammatory, and anticancer activities. Reata Pharmaceuticals is developing omaveloxolone for the treatment of cancers, Friedreich's ataxia and mitochondrial disorders.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Nuclear factor erythroid 2-related factor 2 20 Target ID: CHEMBL1075094 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26170027 \| https://www.ncbi.nlm.nih.gov/pubmed/25897966	Activator 1430
Nuclear factor NF-kappa-B complex 11 Target ID: CHEMBL2094258 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25897966	Inhibitor 8297

Conditions

Condition	Modality	Highest Phase	Product
Friedreich ataxia 12 Sources: http://adisinsight.springer.com/drugs/800039652	Primary	Phase II 1132	Unknown Approved Use Unknown
Mitochondrial myopathy 1 Sources: http://adisinsight.springer.com/drugs/800039652	Primary	Phase II 1132	Unknown Approved Use Unknown
Melanoma 88 Sources: http://adisinsight.springer.com/drugs/800039652	Primary	Phase II 1132	Unknown Approved Use Unknown

Doses

Dose	Population	Adverse events
300 mg 1 times / day multiple, oral Highest studied dose Dose: 300 mg, 1 times / day Route: oral Route: multiple Dose: 300 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/30656180 Page: p.19	unhealthy, ADULT n = 10 Health Status: unhealthy Condition: Friedreich ataxia Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 10 Sources: https://pubmed.ncbi.nlm.nih.gov/30656180 Page: p.19	Sources: https://pubmed.ncbi.nlm.nih.gov/30656180 Page: p.19

Sourcing

Vendor/Aggregator	ID	URL
1PlusChem LLC	1P00AC1P	https://www.1pchem.com/search?query=1P00AC1P
ApexBio Technology	B3576	https://www.apexbt.com/catalogsearch/result/?q=B3576
AstaTech	40810	http://astatechinc.com/CPSResult.php?CRNO=40810
Axon MedChem	2497	https://www.axonmedchem.com/product/2497
Cayman Chemical	17854	http://www.caymanchem.com/app/template/Product.vm/catalog/17854
Chem Scene	CS-3078	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-3078
ChemShuttle	169578	https://www.chemshuttle.com/catalogsearch/result/?q=169578
Excenen	EX-A541	http://www.excenen.com/searchresultlist.php?id=EX-A541
MedChem Express	HY-12212	https://www.medchemexpress.com/search.html?q=HY-12212&ft=&fa=&fp=
MolPort	MolPort-039-193-839	https://www.molport.com/shop/molecule-link/MolPort-039-193-839
MolPort	MolPort-042-665-881	https://www.molport.com/shop/molecule-link/MolPort-042-665-881
MuseChem	I001800	https://www.musechem.com/product/I001800.html
Selleck Chemicals	S7672	http://www.selleckchem.com/search.html?searchDTO.searchParam=S7672
ShangHai Biochempartner	BCP28609	http://www.biochempartner.com/search_BCP28609
Toronto Research Chemicals	D292465	https://www.trc-canada.com/product-detail/?CatNum=D292465
Toronto Research Chemicals	R700990	https://www.trc-canada.com/product-detail/?CatNum=R700990
eMolecules	50283346	https://orderbb.emolecules.com/search/#?query=50283346
eMolecules	75224124	https://orderbb.emolecules.com/search/#?query=75224124
mcule	MCULE-2178019155	https://mcule.com/MCULE-2178019155/

PubMed

Title	Date	PubMed
Molecular mechanisms of Nrf2-mediated antioxidant response.	2009 Feb	18618599
Topical application of the synthetic triterpenoid RTA 408 activates Nrf2 and induces cytoprotective genes in rat skin.	2014 Jul	24362512
Topical application of the synthetic triterpenoid RTA 408 protects mice from radiation-induced dermatitis.	2014 May	24720753
RTA 408, A Novel Synthetic Triterpenoid with Broad Anticancer and Anti-Inflammatory Activity.	2015	25897966

Patents

Sample Use Guides

In Vivo Use Guide

Phase 2 study investigated oral omaveloxolone (RTA-408) (2.5-300 mg capsules) in patients with Friedreich's Ataxia. A Phase 1 healthy volunteer clinical study with RTA 408 Lotion (NCT02029716) consisted of 3 sequential parts. In Part A, RTA 408 Lotion (0.5 %, 1 %, and 3 %) and lotion vehicle were applied to individual 4-cm(2) sites twice daily for 14 days. In Parts B and C, separate groups of subjects had 3 % RTA 408 Lotion applied twice daily to a 100-cm(2) site for 14 days or a 500-cm(2) site for 28 days.

Route of Administration: Other

In Vitro Use Guide

At low concentrations (≤ 25 nM), omaveloxolone (RTA-408) activated Nrf2 and suppressed nitric oxide and pro-inflammatory cytokine levels in interferon-γ-stimulated RAW 264.7 macrophage cells. At higher concentrations, RTA 408 inhibited tumor cell growth (GI50 = 260 ± 74 nM) and increased caspase activity in tumor cell lines, but not in normal primary human cells.

Name

Type

Language

OMAVELOXOLONE

Official Name

English

PROPANAMIDE, N-(2-CYANO-3,12-DIOXO-28-NOROLEANA-1,9(11)-DIEN-17-YL)-2,2-DIFLUORO-

Systematic Name

English

SKYCLARYS

Brand Name

English

OMAVELOXOLONE [USAN]

Common Name

English

RTA 408

Code

English

omaveloxolone [INN]

Common Name

English

RTA-408

Code

English

Omaveloxolone [WHO-DD]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C2080