P2, N=216, Active, not recruiting, EpicentRx, Inc. | Recruiting --> Active, not recruiting | Trial completion date: Oct 2025 --> Oct 2027 | Trial primary completion date: Jul 2025 --> Jul 2027

P1, N=20, Recruiting, University of Nebraska | Trial completion date: Aug 2026 --> Dec 2026 | Trial primary completion date: Aug 2026 --> Dec 2026

Cell viability was quantified using a tetrazolium-based colorimetric assay and apoptosis was evaluated by the Muse® Annexin V & Dead Cell assay based on Annexin V and 7-amino-actinomycin D staining; the expression levels of JNK, p38, ERK, beclin-1, microtubule-associated protein 1 light chain 3B (LC3B), p62/sequestosome 1 (SQSTM1) and poly (ADP-ribose) polymerase (PARP) were assessed by western blotting. Pharmacological inhibition with SP600125 attenuated JNK phosphorylation, reduced apoptotic responses and diminished autophagy-associated marker accumulation, supporting the notion that JNK signaling contributes, at least in part, to these effects. These findings indicate that RTA-408 exerts nanomolar antiproliferative activity in both hormone receptor-positive and triple-negative BC cells through a JNK-dependent mechanism that simultaneously engages apoptosis and autophagy, supporting further in vivo and translational investigation.

Pharmacological activation of NRF2 by dimethyl fumarate (DMF) effectively counteracted the F-53B-induced suppression of GPX4 and FTH1, thereby alleviating ferroptosis and the ensuing cardiotoxicity. Collectively, our findings reveal the synergistic impact of F-53B and DOX on cardiotoxicity and elucidate the underlying mechanism involving the NRF2-mediated anti-ferroptosis pathway.

P=N/A, N=1178, Active, not recruiting, Biogen | Recruiting --> Active, not recruiting

P2, N=210, Not yet recruiting, Merry Life Biomedical Co., Ltd.

Notably, co-administration of brusatol abolished these effects, findings that are consistent with and strongly associated with Nrf2 activation; however, this mechanistic inference is based on pharmacologic inhibition. Collectively, ESA confers robust vascular protection against HCD-induced aortic remodeling and early atherosclerosis-like changes, with these effects being strongly associated with Nrf2 activation.

Additionally, high expression of NOX2 subunit genes and SNAI1 associated with reduced metastasis-free survival. These findings imply that myeloid cell-derived ROS initiate partial EMT in breast cancer cells to promote dissemination and that strategies to target myeloid cell-derived ROS may be explored to limit metastasis.

P1, N=70, Completed, Biogen | Recruiting --> Completed

P1, N=33, Active, not recruiting, Biogen | Trial primary completion date: Feb 2030 --> Sep 2025 | Recruiting --> Active, not recruiting

P=N/A, N=40, Recruiting, Centre Hospitalier Universitaire de Nice | Not yet recruiting --> Recruiting | Trial completion date: Oct 2025 --> Jun 2026 | Trial primary completion date: Sep 2025 --> Jun 2026

Lycorine can directly bind to and inhibit DPP3, thereby blocking the Nrf2 signaling pathway and downregulating SLC7A11. This disruption of GSH metabolism leads to the accumulation of ROS and iron overload, ultimately inducing ferroptosis in CRC cells.