RTA 408
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| Systematic (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 | |
| Clinical data | |
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| Oral, Topical (Dermal), Topical (Ophthalmic) | |
| Identifiers | |
1474034-05-3  | |
| None | |
| PubChem | CID 71811910 |
| Chemical data | |
| Formula | C33H44F2N2O3 |
| 554.33 g/mol | |
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SMILES
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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 RTA 408 possesses antioxidative and anti-inflammatory activities,[1][2] systemic selective radioprotective effects,[3] as well as the ability to improve mitochondrial bioenergetics.[4] RTA 408 is currently under clinical investigation for a variety of indications, including Friedreich’s ataxia, mitochondrial myopathies, immunooncology, prevention of corneal endothelial cell loss following cataract surgery, and for oncology patients at risk of developing radiation dermatitis.
Mechanism of action
The effects of RTA 408 and related synthetic triterpenoid compounds have been documented in over 200 peer-reviewed scientific manuscripts.[5] The mechanism of action of RTA 408 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.[1]
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 mitochondria. Consequently, unlike exogenously administered antioxidants (e.g., vitamin E or Coenzyme Q10), which provide a specific and finite antioxidative potential, RTA 408, through Nrf2, broadly activates intracellular and mitochondrial antioxidative pathways, in addition to pathways that may directly increase mitochondrial biogenesis (such as PGC1α) and bioenergetics.[4]
References
- ↑ 1.0 1.1 Reisman SA, Lee CY, Meyer CJ, Proksch JW, Ward KW (April 15, 2015). "Topical application of the synthetic triterpenoid RTA 408 activates Nrf2 and induces cytoprotective genes in rat skin.". Arch Dermatol Res 306: 447–54. doi:10.1007/s00403-013-1433-7. PMID 24362512.
- ↑ Reisman SA, Lee CY, Meyer CJ et al. (2014). "Topical application of the synthetic triterpenoid RTA 408 protects mice from radiation-induced dermatitis.". Radiat Res 181: 512–20. doi:10.1667/RR13578.1. PMID 24720753.
- ↑ Alexeev V, Lash E, Aguillard A et al. (2014). "Radiation protection of the gastrointestinal tract and growth inhibition of prostate cancer xenografts by a single compound.". Mol Cancer Ther. doi:10.1158/1535-7163.MCT-14-0354. PMID 25398830.
- ↑ 4.0 4.1 Neymotin A, Calingasan NY, Wille E et al. (2011). "Neuroprotective effect of Nrf2/ARE Activators, CDDO-ethylamide and CDDO-trifluoroethylamide in a Mouse Model of Amyotrophic Lateral Sclerosis". Free Radic Biol Med 51: 88–96. doi:10.1016/j.freeradbiomed.2011.03.027. PMC 3109235. PMID 21457778.
- ↑ "Pubmed Search". April 15, 2015. Retrieved April 15, 2015.