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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

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10.1179/1476830514Y.0000000110 110 Navarro-CruzA