Omaveloxolone (RTA-408) is an antioxidant inflammation modulator (AIM), which activates Nrf2 and suppresses nitric oxide (NO)[1]. Omaveloxolone is usually used in research related to inflammation, oxidative stress and Friedreich Ataxia [2][3].
In vitro, Omaveloxolone (0.15-4.8μM; 24h) induced ferroptosis in cisplatin-resistant A549/DDP lung adenocarcinoma cells, downregulated WWP1, stabilized NCOA4, promoted ferritinophagy, and triggered iron overload, lipid peroxidation, and cell death[4]. Omaveloxolone (0-500nM; 72h) reduced cell viability in EB-associated SCC cell lines and normal human epidermal keratinocytes in a dose-dependent manner[5].
In vivo, Omaveloxolone (17.5mg/kg/day; i.p.; 3 days) significantly increased 35-day survival and restored normal hematopoietic stem and progenitor cell frequency and function in C57BL/6 mice exposed to 7.5 Gy total body irradiation[6]. Omaveloxolone (100μg/kg; i.p.; 24h before surgery) significantly reduced serum creatinine and blood urea nitrogen levels, decreased renal tubular necrosis and ROS production, and enhanced Nrf2 nuclear translocation and GSH-related antioxidant gene expression in Nrf2-deficient male C57BL/6J mice subjected to unilateral renal ischemia-reperfusion injury[7].
References:
[1] Probst BL, Trevino I, McCauley L, et al. RTA 408, A Novel Synthetic Triterpenoid with Broad Anticancer and Anti-Inflammatory Activity. PLoS One. 2015;10(4):e0122942.
[2] Hao J, Zhou J, Hu S, et al. RTA 408 ameliorates diabetic cardiomyopathy by activating Nrf2 to regulate mitochondrial fission and fusion and inhibiting NF-κB-mediated inflammation. Am J Physiol Cell Physiol. 2024;326(2):C331-C347.
[3] Lee A. Omaveloxolone: First Approval. Drugs. 2023;83(8):725-729.
[4] Wang X, Liu T, Fei Y, et al. RTA-408 overcomes cisplatin-resistant lung cancer by inhibiting WWP1-mediated NCOA4 ubiquitination to induce ferritinophagy and ferroptosis. Free Radic Biol Med. 2025;238:595-610.
[5] Cohen-Nowak AJ, Cohen AJ, Correia ED, Portocarrero CP, South AP, Nikbakht N. Omaveloxolone attenuates squamous cell carcinoma growth and disease severity in an Epidermolysis Bullosa mouse model. Exp Dermatol. 2022;31(7):1083-1088.
[6] Goldman DC, Alexeev V, Lash E, Guha C, Rodeck U, Fleming WH. The triterpenoid RTA 408 is a robust mitigator of hematopoietic acute radiation syndrome in mice. Radiat Res. 2015;183(3):338-344.
[7] Han P, Qin Z, Tang J, et al. RTA-408 Protects Kidney from Ischemia-Reperfusion Injury in Mice via Activating Nrf2 and Downstream GSH Biosynthesis Gene. Oxid Med Cell Longev. 2017;2017:7612182.
Omaveloxolone (RTA-408)是一种抗氧化炎症调节剂（AIM），可激活Nrf2并抑制一氧化氮（NO）的生成[1]。Omaveloxolone常用于炎症、氧化应激以及弗里德赖希共济失调相关的研究[2][3]。
体外实验中，Omaveloxolone（0.15-4.8μM；24小时）可在顺铂耐药的A549/DDP肺腺癌细胞中诱导铁死亡，表现为下调WWP1、稳定NCOA4、促进铁蛋白自噬，并引发铁过载、脂质过氧化和细胞死亡[4]。Omaveloxolone（0-500nM；72小时）还可剂量依赖性地降低EB相关鳞状细胞癌细胞及正常人表皮角质形成细胞的活力[5]。
体内实验中，Omaveloxolone（17.5mg/kg/天；腹腔注射；连续3天）显著提高了接受7.5 Gy全身照射的C57BL/6小鼠35天存活率，并恢复了其正常的造血干/祖细胞频率与功能[6]。Omaveloxolone（100μg/kg；腹腔注射；手术前24小时）显著降低了单侧肾缺血再灌注损伤Nrf2缺失雄性C57BL/6J小鼠的血清肌酐和尿素氮水平，减少肾小管坏死和ROS生成，并增强了Nrf2核转位及GSH相关抗氧化基因的表达[7]。