ML210

These findings demonstrate that ML210 potentiates Tempol's pro-oxidant pressure by targeting GPX4, selectively amplifying H2O2 accumulation and ER stress engagement without collapsing global redox balance. This study provides mechanistic rationale for redox-proteostasis co-targeting in gastric and colon cancers and establishes a foundation for in vivo validation.

In the CT26 mouse model, ML210-loaded prodrug nanoassemblies demonstrated superior antitumor effects. The strategy-using prodrug as "carriers" for ferroptosis inducers-offers a promising approach for synergistic antitumor therapy.

Our results indicate that TXNIP is a key player in ferroptotic pathway, as its deletion conferred resistance to classic ferroptosis-inducing agents (erastin, RSL3, and ML210), while TXNIP overexpression increased their susceptibility to ferroptosis. Our findings suggest that TXNIP acts as a positive regulator of ferroptosis by modulating autophagy and iron availability. Targeting TXNIP might hold promise in developing drugs for diseases involving the ferroptotic pathway.

ML210-ansaFc exhibited robust tumor growth suppression in 3D spheroid models, coupled with favorable drug-like properties, highlighting its potential as a therapeutic agent for intractable cancers. This work could pave the way for the development of metallocene-based chemotypes with diverse spatial configurations for the treatment of multiple diseases.

The combined application of GPx4 and Mitogen-activated protein kinase kinase (MEK) inhibitors, namely ML210 and trametinib, respectively, reduced lethality and tumor-like phenotypes in these flies. Notably, this combination treatment synergistically suppressed the proliferation of human PDAC cells and their corresponding xenografts in mice by inducing ROS accumulation, which triggered ferroptosis. These results suggest that inducing ferroptosis could represent a promising therapeutic strategy for PDAC.

The oxidization of the cell membrane lipids may suppress EMT, including cell migration. Since EMT is a major malignant phenotype of PDAC, our findings may lead to the advancement of PDAC therapy, especially in the prevention of postoperative recurrence.

The inhibition of ANXA8 amplified the susceptibility of CESC cells to Erastin and sorafenib-induced ferroptosis, whereas it exerted minimal influence on DPI7 and DPI10-induced ferroptosis. However, this inhibitory effect could be reversed by ANXA8 overexpression. Therefore, our research suggests that the TFAP2A/ANXA8 axis exerts regulatory control over ferroptosis in CESC cells by mediating GSH synthesis in System Xc.

We found that eribulin-induced cell death was reduced by ferroptosis inhibitors; deferoxamine, an iron chelator and ferrostatin-1, a lipid peroxidation inhibitor...The combination of eribulin and ML210, a glutathione peroxidase 4-inhibiting ferroptosis inducer, had a synergistic effect on ferroptosis. Taken together, our findings show firstly that eribulin triggers ferroptosis in OCCC and this effect occurs via the suppression of the Nrf2-HO-1 signaling pathway, SOD activity and the promotion of lipid peroxidation. These findings suggest that eribulin-induced ferroptosis is associated with its anti-tumor effect and also could be a potential therapeutic target in OCCC.

Importantly, A16 exhibited superior selectivity and potency compared to reported GPX4 inhibitors, ML210 and ML162. This provides the structural diversity of tool probes for unraveling the fundamental biology of GPX4 and exploring the therapeutic potential of pancreatic cancer via ferroptosis induction.

To address this issue, this work describes a promising photosensitizer ENBS-ML210 and its application against hypoxia of NSCLC treatment based on type I photodynamic therapy and glutathione peroxidase 4 (GPX4)-targeted ferroptosis...Finally, the excellent synergistic antitumor effects are confirmed both in vitro and in vivo. We firmly believe that this method will provide a new direction for the clinical treatment of NSCLC in the future.