TABLE 1.
Summary of Nrf2 modulators evaluated in cellular and animal models, as well as in samples from patients affected by inherited metabolic disorders (IMD).
| Compound | IMD | Effects | Active/completed clinical trials | References |
| Dimethyl fumarate (DMF) | X-linked Adrenoleukodystrophy (X-ALD) | Promotes Nrf2 nuclear translocation by interacting with Keap1 cysteine residues. Increases Nrf2 mRNA levels. | – | Ranea-Robles et al., 2018 |
| Friedreich’s ataxia (FRDA) | Hayashi and Cortopassi, 2016; Jasoliya et al., 2019; Petrillo et al., 2019 | |||
| Sulforaphane (SFN) | Friedreich’s ataxia (FRDA) | Promotes Nrf2 nuclear translocation by interacting with Keap1 cysteine residues. Increases Nrf2 mRNA levels. | – | Abeti et al., 2015; Petrillo et al., 2017, 2019; La Rosa et al., 2019, 2021 |
| TBE-31 | Friedreich’s ataxia (FRDA) | Promotes Nrf2 nuclear translocation by interacting with Keap1 cysteine residues. Increases Nrf2 mRNA levels. | – | Abeti et al., 2015 |
| RTA 408 (Omaveloxolone; Omav) | Friedreich’s ataxia (FRDA) | Promotes Nrf2 nuclear translocation by interacting with Keap1 cysteine residues. Increases Nrf2 mRNA levels. | Phase II clinical trial (ClinicalTrials.gov Identifier: NCT02255435; MOXIe) | Abeti et al., 2018; Lynch et al., 2018, 2021; Petrillo et al., 2019 |
| N-acetylcysteine (NAC) | Friedreich’s ataxia (FRDA) | Antioxidant that induces Nrf2 expression. | – | Petrillo et al., 2019 |
| EPI-743 | Friedreich’s ataxia (FRDA) | Promotes Nrf2 nuclear translocation. Increase Nrf2 mRNA levels. | – | La Rosa et al., 2019, 2021; Petrillo et al., 2019 |
| Idebenone | Friedreich’s ataxia (FRDA) | CoQ10 analog that induces Nrf2 expression. | – | Petrillo et al., 2019 |
| Dyclonine | Friedreich’s ataxia (FRDA) | Activates the ARE/Nrf2 pathway, by enhanced binding of Nrf2 to ARE sites. | – | Sahdeo et al., 2014 |