P2/3, N=372, Completed, University Hospital, Lille | Active, not recruiting --> Completed

Moreover, DFP-derived PROTACs elicited enhanced cancer cell selective antiproliferative activities and intracellular on-target effects, downregulating several KDMs implicated in the etiology of BCa cells, including a strong degradation of KDMs 2A, 3A and 5B, and a moderate degradation of KDMs 4A-C, 5C, 6B. Collectively, our data supports KDM inhibition as a key mechanism of anticancer activity of DFP and identifies PROTAC is a viable strategy to obtain novel DFP analogs with improved potency and therapeutic index.

Not just increasing ALA-PpIX levels, Lap enhanced PpIX localization in the mitochondria and promoted mitochondria-mediated apoptosis after PDT in the H4 cell line with strong ABCG2 activities. Our results demonstrate that blocking ABCG2-mediated PpIX efflux is critical for the enhancement of ALA and, in tumor cells with ABCG2 activities, inhibiting PpIX bioconversion by DFO needs to be combined with PpIX efflux suppression for effective enhancement of ALA.

Furthermore, the administration of deferoxamine (DFO), an oral iron chelator, induced a decrease in intracellular iron and suppressed the proliferation of ESCC cell lines and an increase in caspase 3 and 7 activity, indicating the induction of apoptosis...Finally, we confirmed that the deficiency of iron in ESCC cell lines induced an increase in TfR expression via upregulation of iron regulatory protein 2. These findings suggest that TfR is an independent prognostic factor in ESCC and that targeting iron metabolism may be a promising therapeutic approach for improving ESCC treatment outcomes.

These effects were reversed by the ferroptosis inhibitors ferrostatin‑1 and deferoxamine...Silencing of YAP led to the downregulation of its downstream targets, ACSL4 and TfR, even in the presence of Sch A. In vivo, Sch A significantly inhibited subcutaneous tumor growth in nude mice. In conclusion, Sch A may activate the YAP/ACSL4/TfR signaling axis to induce ferroptosis in NSCLC cells, positioning it as a potential small‑molecule therapeutic agent for NSCLC.

P1/2, N=66, Recruiting, Duke University | Trial completion date: May 2026 --> Oct 2026 | Trial primary completion date: Nov 2025 --> Apr 2026

This study is the first to propose that tectorigenin functions as a novel agent that induces ferroptosis in bladder cancer by targeting EGFR. Our findings reveal a novel therapeutic mechanism and lay the groundwork for developing targeted treatments for bladder cancer.

P2/3, N=240, Not yet recruiting, University of Illinois at Chicago | Phase classification: P2 --> P2/3 | N=63 --> 240 | Initiation date: Nov 2025 --> Mar 2026

Ferroptosis plays a critical role in the pathogenesis of sepsis-induced liver injury. Targeting the activation of ferroptosis in hepatocytes during sepsis through intervention with DFO may represent a promising therapeutic strategy for the management of this condition.

Critically, OZO-induced growth inhibition in melanoma cells was prevented by ferroptosis inhibitors (ferrostatin-1 and deferiprone), but not by inhibitors of apoptosis or necroptosis. Taken together, these findings offer new therapeutics strategy for treating melanoma by inducing ferroptosis.

P2, N=90, Recruiting, Pharmacosmos A/S | Trial completion date: Dec 2024 --> May 2028 | Trial primary completion date: Jul 2024 --> Oct 2027

Indeed, we found cytotoxic effects of AQ on GSCs were potentiated when combined with the iron chelator deferoxamine (DFO)...Importantly, we found that AQ treatment alone or in combination with iron chelators impaired cholesterol homeostasis in GSCs, leading to mitochondrial fragmentation and cell death. These findings suggest AQ in combination with iron chelators results in lethal disruption of cholesterol metabolism in glioma stem cells.