ArticleJournal of ovarian research2026
Mechanistic insights into a novel GPX4 inhibitor Compound AI-3p reversing cisplatin-resistance in ovarian cancer cells.
Article in Journal of ovarian research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
3 citing papers in PubMed.
- Cisplatin resistance in ovarian cancer: exploration and insights from metal ion homeostasis imbalance.Frontiers in cell and developmental biology · 2026Review
- Metabolic control of ferroptosis in cancer: lipid dependencies as therapeutic vulnerabilities.Frontiers in oncology · 2026Review
- Advancing the frontiers of ovarian cancer therapy: a comprehensive synthesis of emerging cell death paradigms.Oncology reviews · 2026Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors.
Funding
Abstract
backgroundFerroptosis has been correlated with the cancer chemotherapy resistance, and inducing ferroptosis has been demonstrated to reverse drug resistance. The GPX4-mediated signaling pathway is one of the most central pathways regulating ferroptosis. However, most currently available GPX4 inhibitors are covalent inhibitors, with limited structural diversity.
resultsHere, we explored the potential and related molecular mechanisms of Compound AI-3p, a novel GPX4 inhibitor designed by linking an isoxazole pharmacophore to an anthraquinone core, for the treatment of cisplatin (DDP)-resistant ovarian cancer. Compound AI-3p showed significant cytotoxicity against DDP-resistant ovarian cancer cells (SKOV3/DDP), with a higher selectivity index against SKOV3/DDP and lower cytotoxicity against normal ovarian epithelial cells (IOSE80) than DDP. Molecular docking revealed that AI-3p forms a hydrogen bond with Leu130 in the catalytically active tetramer of GPX4, as well as carbon-hydrogen bonds with Sec 46, Gln81, and Lys135. Further validation via molecular dynamics simulations and Cellular Thermal Shift Assay (CETSA) confirmed that AI-3p can form a stable complex with GPX4. Mechanistic study revealed that Compound AI-3p could trigger the ferroptosis via inhibition of the GPX4/GSH axis, inducing reactive oxygen species (ROS) production, Lipid peroxidation, iron ion accumulation, Labile Iron Pool accumulation (LIP) accumulation, and a reduction in GSH content.
conclusionsThis study identifies Compound AI-3p as a novel GPX4 inhibitor that triggers ferroptosis, offering a potential breakthrough in the development of future drugs to combat cisplatin-resistant ovarian cancer development.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.