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Original Research

Pharmacokinetics and pharmacodynamics of the novel Nrf2 activator omaveloxolone in primates

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Pages 1259-1270 | Published online: 17 Apr 2019

References

  • LibyKTSpornMBSynthetic oleanane triterpenoids: multifunctional drugs with a broad range of applications for prevention and treatment of chronic diseasePharmacol Rev2012644972100310.1124/pr.111.00484622966038
  • KerinsMJOoiAThe roles of NRF2 in modulating cellular iron homeo-stasisAntioxid Redox Signal2018291756177310.1089/ars.2017.717628793787
  • LiskCMcCordJBoseSNrf2 activation: a potential strategy for the prevention of acute mountain sicknessFree Radic Biol Med20136326427310.1016/j.freeradbiomed.2013.05.02423722164
  • WuKCCuiJYKlaassenCDBeneficial role of Nrf2 in regulating NADPH generation and consumptionToxicol Sci2011123259060010.1093/toxsci/kfr18321775727
  • HayesJDDinkova-KostovaATThe Nrf2 regulatory network provides an interface between redox and intermediary metabolismTrends Biochem Sci201439419921810.1016/j.tibs.2014.02.00224647116
  • LudtmannMHAngelovaPRZhangYAbramovAYDinkova-KostovaATNrf2 affects the efficiency of mitochondrial fatty acid oxidationBiochem J2014457341542410.1042/BJ2013086324206218
  • HolmstromKMBairdLZhangYNrf2 impacts cellular bioenergetics by controlling substrate availability for mitochondrial respirationBiol Open20132876177010.1242/bio.2013485323951401
  • HolmstromKMKostovRVDinkova-KostovaATThe multifaceted role of Nrf2 in mitochondrial functionCurr Opin Toxicol20161809110.1016/j.cotox.2016.10.00228066829
  • ShanYSchoenfeldRAHayashiGFrataxin deficiency leads to defects in expression of antioxidants and Nrf2 expression in dorsal root ganglia of the Friedreich’s ataxia YG8R mouse modelAntioxid Redox Signal201319131481149310.1089/ars.2012.453723350650
  • AnzovinoAChiangSBrownBEHawkinsCLRichardsonDRHuangMLMolecular alterations in a mouse cardiac model of Friedreich ataxia: an impaired Nrf2 response mediated via upregulation of Keap1 and activation of the Gsk3beta axisAm J Pathol2017187122858287510.1016/j.ajpath.2017.08.02128935570
  • D’OriaVPetriniSTravagliniLFrataxin deficiency leads to reduced expression and impaired translocation of NF-E2-related factor (Nrf2) in cultured motor neuronsInt J Mol Sci20131447853786510.3390/ijms1404785323574943
  • KraftADLeeJMJohnsonDAKanYWJohnsonJANeuronal sensitivity to kainic acid is dependent on the Nrf2-mediated actions of the antioxidant response elementJ Neurochem20069861852186510.1111/j.1471-4159.2006.04019.x16945104
  • Shekh-AhmadTEckelRDayalan NaiduSKEAP1 inhibition is neuroprotective and suppresses the development of epilepsyBrain201814151390140310.1093/brain/awy07129538645
  • PuccioHAnheimMTranchantCPathophysiogical and therapeutic progress in Friedreich ataxiaRev Neurol (Paris)2014170535536510.1016/j.neurol.2014.03.00824792433
  • AbetiRBaccaroAEsterasNGiuntiPNovel Nrf2-inducer prevents mitochondrial defects and oxidative stress in Friedreich’s ataxia modelsFront Cell Neurosci20181218810.3389/fncel.2018.0018830065630
  • LynchDRFarmerJHauserLSafety, pharmacodynamics, and potential benefit of omaveloxolone in Friedreich ataxiaAnn Clin Transl Neurol201961152610.1002/acn3.66030656180
  • ReismanSAGoldsberryARLeeCYTopical application of RTA 408 lotion activates Nrf2 in human skin and is well-tolerated by healthy human volunteersBMC Dermatol2015151010.1186/s12895-015-0029-726170027
  • ReismanSALeeCYMeyerCJProkschJWWardKWTopical application of the synthetic triterpenoid RTA 408 activates Nrf2 and induces cytoprotective genes in rat skinArch Dermatol Res2014306544745410.1007/s00403-013-1433-724362512
  • ReismanSAYeagerRLYamamotoMKlaassenCDIncreased Nrf2 activation in livers from Keap1-knockdown mice increases expression of cytoprotective genes that detoxify electrophiles more than those that detoxify reactive oxygen speciesToxicol Sci20091081354710.1093/toxsci/kfn26719129213
  • CreelanBCGabrilovichDIGrayJESafety, pharmacokinetics, and pharmacodynamics of oral omaveloxolone (RTA 408), a synthetic triterpenoid, in a first-in-human trial of patients with advanced solid tumorsOnco Targets Ther2017104239425010.2147/OTT.S13699228919776
  • HanPQinZTangJRTA-408 protects kidney from ischemia-reperfusion injury in mice via activating Nrf2 and downstream GSH biosynthesis geneOxid Med Cell Longev20172017761218210.1155/2017/761218229435098
  • AbetiRUzunERenganathanIHondaTPookMAGiuntiPTargeting lipid peroxidation and mitochondrial imbalance in Friedreich’s ataxiaPharmacol Res20159934435010.1016/j.phrs.2015.05.01526141703
  • PaupeVDassaEPGoncalvesSImpaired nuclear Nrf2 trans-location undermines the oxidative stress response in Friedreich ataxiaPLoS One200941e425310.1371/journal.pone.000425319158945
  • WildACMulcahyRTRegulation of gamma-glutamylcysteine synthetase subunit gene expression: insights into transcriptional control of antioxidant defensesFree Radic Res200032428130110741850