ArticlePloS one2015
RTA 408, A Novel Synthetic Triterpenoid with Broad Anticancer and Anti-Inflammatory Activity.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers.
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Who cites it
68 citing papers in PubMed, 97 citations in OpenAlex.
- Simvastatin as a Potential Disease-Modifying Therapy for Patients with Parkinson's Disease: Rationale for Clinical Trial, and Current Progress.Journal of Parkinson's disease · 2017Trial
- RTA‑408 induces p38‑dependent apoptosis and suppresses cell viability in hepatocellular carcinoma cells.Hepatic oncology · 2026Article
- Unique fluoroalkyl substituents: is there life after CFChemical science · 2026Review
- RTA-408 induces JNK-dependent apoptosis and autophagy in breast cancer cells.Oncology letters · 2026Article
- RTA-408 Enhances Radiosensitivity and Inhibited Tumor Progression via JNK Pathway in Glioblastoma.The Kaohsiung journal of medical sciences · 2026Article
- Sex-based differences in the NRF2 oxidative stress response: Implications for precision therapeutics.Redox biology · 2026Review
- Wise as a Serpent and Gentle as a Dove: Pharmacological Targeting of NRF2/KEAP1 Pathway from Treasure Trove of Mother Nature.Drug design, development and therapy · 2026Review
- Emerging targeted therapies for chronic obstructive pulmonary disease: from symptom control to precision medicine.Frontiers in pharmacology · 2026Review
- Ferroptosis is a novel pathogenic mechanism of FDXR-related disease via disruption of the NRF2 pathway.Cell death discovery · 2025Article
- Modulation of Nrf2 and Mitochondrial Function: Pharmacological Implications.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Synthesis and Biological Profile of Omaveloxolone: The Cornerstone for Friedreich Ataxia Treatment.International journal of molecular sciences · 2025Review
- Natural Killer Cell-Mediated Antitumor Immunity: Molecular Mechanisms and Clinical Applications.MedComm · 2025Review
- Recapitulating dengue virus infection with human pluripotent stem cell-derived liver organoids for antiviral screening.Nature communications · 2025Article
- KIAA1429 Silencing ameliorates osteosarcoma progression through promoting ferroptosis via Nrf2/NQO1 axis.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025Article
- Oxidative stress in cancer: from tumor and microenvironment remodeling to therapeutic frontiers.Molecular cancer · 2025Review
- Therapeutic potential of NRF2 activating drug RTA-408 in suppressing T cell effector responses and inflammatory bowel disease.Journal of immunology (Baltimore, Md. : 1950) · 2025Article
- Clinical Assessment of the Drug-Drug Interaction Potential of Omaveloxolone in Healthy Adult Participants.Journal of clinical pharmacology · 2025Article
- Omaveloxolone Suppresses Cell Growth and Causes Cell Cycle Arrest by Downregulating CDC20 Expression in Glioblastoma Cells Both In Vitro and In Vivo.Journal of cellular and molecular medicine · 2025Article
- Omaveloxolone Ameliorates Cognitive Deficits by Inhibiting Apoptosis and Neuroinflammation in APP/PS1 Mice.Molecular neurobiology · 2025Article
- An Azomethine Derivative, 1-(4-nitrophenyl)-N-phenylmethanimine (BCS2) Ameliorated 7,12-dimethylbenz(a)anthracene-induced Mammary Carcinoma through Nrf2-Keap1-HO-1 Pathway.Current medicinal chemistry · 2025Article
8 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Semi-synthetic triterpenoids are antioxidant inflammation modulator (AIM) compounds that inhibit tumor cell growth and metastasis. Compounds in the AIM class bind to Keap1 and attenuate Nrf2 degradation. In the nucleus, Nrf2 increases antioxidant gene expression and reduces pro-inflammatory gene expression. By increasing Nrf2 activity, AIMs reduce reactive oxygen species and inflammation in the tumor microenvironment, which reverses tumor-mediated immune evasion and inhibits tumor growth and metastasis. AIMs also directly inhibit tumor cell growth by modulating oncogenic signaling pathways, such as IKKβ/NF-κB. Here, we characterized the in vitro antioxidant, anti-inflammatory, and anticancer activities of RTA 408, a novel AIM that is currently being evaluated in patients with advanced malignancies. At low concentrations (≤ 25 nM), RTA 408 activated Nrf2 and suppressed nitric oxide and pro-inflammatory cytokine levels in interferon-γ-stimulated RAW 264.7 macrophage cells. At higher concentrations, RTA 408 inhibited tumor cell growth (GI50 = 260 ± 74 nM) and increased caspase activity in tumor cell lines, but not in normal primary human cells. Consistent with the direct effect of AIMs on IKKβ, RTA 408 inhibited NF-κB signaling and decreased cyclin D1 levels at the same concentrations that inhibited cell growth and induced apoptosis. RTA 408 also increased CDKN1A (p21) levels and JNK phosphorylation. The in vitro activity profile of RTA 408 is similar to that of bardoxolone methyl, which was well-tolerated by patients at doses that demonstrated target engagement. Taken together, these data support clinical evaluation of RTA 408 for cancer treatment.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.