P1, N=41, Terminated, Novartis Pharmaceuticals | N=140 --> 41 | Trial completion date: Jul 2027 --> Oct 2025 | Recruiting --> Terminated | Trial primary completion date: Jul 2027 --> Oct 2025; The trial was terminated due to a business decision and not as a result of any safety concerns

To validate the regulatory effect of chicoric acid on the Nrf2/Notch1 axis, rescue experiments were conducted using ML385 (an Nrf2 inhibitor) and DAPT (a Notch inhibitor) to assess their impact on the pharmacological efficacy of chicoric acid. Collectively, the advantageous impacts of chicoric acid on salpingitis rats have been linked to the suppression of necroptosis via the Nrf2/Notch1 axis.

P1, N=22, Active, not recruiting, Washington University School of Medicine | Recruiting --> Active, not recruiting | Trial completion date: Apr 2026 --> Aug 2025 | Trial primary completion date: Apr 2026 --> Jul 2025

Importantly, DMF enhanced sorafenib's antitumor effects. Collectively, our results demonstrate new mechanism insights into the antitumor effects of DMF and that Nrf2-targeted therapy might improve HCC treatment outcomes.

Mechanistic studies indicated that TBII inhibited the ethanol-induced increase in KEAP1 and reversed the ethanol-induced changes in NRF2 and its downstream targets. In conclusion, this study suggests that TBII may become a potential therapeutic agent for ALD by modulating the KEAP1-NRF2 pathway to alleviate oxidative stress and lipid metabolism abnormalities.

Moreover, ML385 was found to reduce the expression of LDHA, glucose uptake, and the levels of lactate derived from glycolysis. Overall, these results suggest that Nrf2 functions as an oncogene in ATL and may represent a promising therapeutic target.

Taken together, our work uncovers a new mechanism by which ShtIX induced ferroptosis through inhibition the Nrf2 pathway and activation of NCOA4-mediated ferritinophagy in NSCLC cells. Targeting ferritinophagy to regulate ferroptosis offers a novel therapeutic strategy for the treatment of lung cancer with ShtIX.

In vivo, ML385 also promoted the killing effect of radiation on xenografted tumours in nude mice. This study identifies NRF2 inhibitor ML385 as a radiosensitizer of ESCC, which highlights the therapeutic potential of the NRF2-SLC7A11 pathway and provides a deeper understanding of the mechanism of ferroptosis in esophageal squamous cell carcinoma.

In this investigation, the treatment with solasodine and doxorubicin combination showed a notable increase in intracellular ROS generation in KBChR-8-5 cells...Additionally, the combination therapy increased the lipid peroxidation levels while simultaneously reducing the activities of antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and the levels of glutathione (GSH). These results demonstrated that solasodine disrupts redox balance, and overcomes drug resistance by downregulating P-gp via regulating Nrf2/Keap1 signaling pathway in MDR cancer cells.

In this study, we discovered that celastrol stimulates an abnormal rise in the reactive oxygen species (ROS) level in lung cancer cells and that the ROS scavenger N-acetylcysteine (NAC) could counteract the cell death caused by celastrol...Above all, our study found that ML385 enhanced celastrol-induced increases in ROS and ER stress, leading to lung cancer cell death. This research provides a potential strategy for the preclinical investigation of celastrol.

It is demonstrated that EZ@TD synergistically inhibited tumor growth and activated the antitumor immune response by inhibiting the Nrf2/ARE signaling pathway in tumors. We provide a new paradigm for amplifying intracellular oxidative stress by interfering with various signaling pathways.

Additionally, the expression of NRF2-regulated antioxidant and detoxification genes including SOD2, HMOX2, and GSS was maintained upon ML-385 treatment. In conclusion, our results demonstrated that all the studied inhibitors, namely K67, retinoic acid, and ML-385, increased the efficacy of doxorubicin in doxorubicin-resistant HL-60/DR cells, and suggested a potential strategy of combination therapy using NRF2 inhibitors and doxorubicin in overcoming doxorubicin resistance in leukemia.