Inducing Programmed Cell Deaths via Targeting TXNRD1/2 or GPX4

Dear Colleagues,

Selenoproteins, e.g., thioredoxin reductase (TXNRD) and glutathione peroxidase (GPX), play central roles in regulating cellular redox homeostasis. In recent years, the connections between the TXNRD and GPX and programmed cell deaths have been intensively established. The connections of these proteins to cell deaths are of pathological significance in maintaining phenotypes of various diseases and/or contributing to drug resistance. GPX4 is predominant for cellular ferroptosis defense by converting phospholipid hydroperoxides to phospholipid alcohol. Meanwhile, TXNRD is associated with the processes of reducing cystine sourced from system x_c¯ to cysteine. Thus, an increasing number of natural or synthetic TXNRD or GPX4 inhibitors have been reported to suppress tumor growth by inducing ROS-dependent apoptosis or/and emerging ferroptosis. Considering these findings, targeting selenoprotein TXNRD or GPX4 has been recognized as a promising strategy for cancer therapy and/or sensitizing tumor cells to chemotherapeutic drugs.

The aim of this Special Issue is to collect the latest advances in targeting TXNRD of GPX4 in the cytosol and/or the mitochondria for the induction of programmed cell deaths (e.g., apoptosis, ferroptosis, necroptosis, autophagy, pyroptosis, etc.) and cancer treatment. Both review articles and original research articles are welcome. This Special Issue includes, but is not limited to, the following topics:

1. Screening and discovery of novel drugs targeting TXNRD/GPX4;
2. Design and synthesis of small molecules or metal complexes targeting TXNRD/GPX4;
3. Pharmacological mechanism or signaling pathways of drugs targeting TXNRD/GPX4;
4. Synergistic effects of TXNRD/GPX4 inhibitors with chemotherapeutic drugs;
5. Overcoming tumor drug resistance by inhibiting TXNRD/GPX4;
6. Metabolic reprogramming in cancer cells induced by targeting TXNRD/GPX4;
7. Novel assays for screening effective TXNRD/GPX4 inhibitors;
8. Novel probes for visualizing TXNRD/GPX4 functions.

Dr. Jianqiang Xu
Prof. Dr. Jianguo Fang
Guest Editors

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• thioredoxin reductase (TXNRD)
• glutathione peroxidase (GPX)
• selenoprotein
• reactive oxygen species (ROS) programmed cell death
• metal complex
• ferroptosis
• apoptosis
• necroptosis
• autophagy