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And then comes the part that makes this story so strange

The emergence of new technologies like spatial transcriptomics and spatial metabolomics offers hope for identifying more potential metabolites in animal models, although effectively applying these methods to human samples remains a significant challenge

Two complementary lineagessystem Xc inhibitors and GPX4-directed agentsoffer improvements in potency, stability, or solubility, yet translation is constrained by on-target depletion of cystine and glutathione in normal tissues and by off-target perturbations, including mitochondrial channel engagement and p53 pathway modulation, which collectively narrow the therapeutic index

In addition, GPX4 has been shown to govern lipoxygenases activities in the AA metabolism ( 4 , 12-HETE, and 15-HETE) in the presence of GPX4 activator compound 102 ( Supplementary Figure S3B )

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