Omaveloxolone

Omaveloxolone

Clinical data
Synonyms	RTA 408
Routes of administration	Oral, Topical (Ophthalmic)
ATC code	none
Legal status
Legal status	Investigational
Identifiers
IUPAC name N-((4aS,6aR,6bS,8aR,12aS,14aR,14bS)-1 1-cyano-2,2,6a,6b,9,9,12a-heptamethyl-10,14-dioxo-1,2,3,4,4a,5,6,6a,6b,7,8,8a,9,10,12a,14,14a,14b- octadecahydropicen-4a-yl)-2,2-difluoropropanamide
CAS Number	1474034-05-3 Y
PubChem CID	71811910
IUPHAR/BPS	7573
ChemSpider	34980948 Y
UNII	G69Z98951Q
Chemical and physical data
Formula	C33H44F2N2O3
Molar mass	554.33 g/mol
3D model (JSmol)	Interactive image
SMILES O=C4C(\C#N)=C/[C@@]5(/C3=C/C(=O)[C@H]2[C@](CC[C@@]1(NC(=O)C(F)(F)C)CCC(C)(C)C[C@H]12)(C)[C@]3(C)CC[C@H]5C4(C)C)C
InChI InChI=1S/C32H43NO4/c1-27(2)11-13-32(26(36)37-8)14-12-31(7)24(20(32)17-27)21(34)15-23-29(5)16-19(18-33)25(35)28(3,4)22(29)9-10-30(23,31)6/h15-16,20,22,24H,9-14,17H2,1-8H3/t20-,22-,24-,29-,30+,31+,32-/m0/s1 Y Key:WPTTVJLTNAWYAO-KPOXMGGZSA-N Y
NY (what is this?)

Omaveloxolone (RTA 408) is a second generation member of the synthetic oleanane triterpenoid compounds and currently in clinical development by Reata Pharmaceuticals. Preclinical studies have demonstrated that omaveloxolone possesses antioxidative and anti-inflammatory activities and the ability to improve mitochondrial bioenergetics. Omaveloxolone is currently under clinical investigation for a variety of indications, including Friedreich’s ataxia, , immunooncology, and prevention of corneal endothelial cell loss following cataract surgery.

The effects of omaveloxolone and related synthetic triterpenoid compounds have been documented in over 200 peer-reviewed scientific manuscripts. The mechanism of action of omaveloxolone and its related compounds has been demonstrated to be through a combination of activation of the antioxidative transcription factor Nrf2 and inhibition of the pro-inflammatory transcription factor NF-κB.

Nrf2 transcriptionally regulates multiple genes that play both direct and indirect roles in producing antioxidative potential and the production of cellular energy (i.e., adenosine triphosphate or ATP) within the . Consequently, unlike exogenously administered antioxidants (e.g., vitamin E or Coenzyme Q10), which provide a specific and finite antioxidative potential, omaveloxolone, through Nrf2, broadly activates intracellular and mitochondrial antioxidative pathways, in addition to pathways that may directly increase (such as PGC1α) and bioenergetics.