NSC59984

NSC59984 is a small molecule p53 pathway restorer that targets mutant p53 for ubiquitin-mediated degradation while simultaneously activating p73-dependent signaling. It induces reactive oxygen species (ROS) and promotes ROS-dependent apoptosis in cancer cells. In pre-clinical models of pancreatic and colorectal cancer, NSC59984 has demonstrated the ability to stimulate mitochondria-dependent ferroptosis, particularly when used in combination with other ferroptosis inducers or cystine deprivation. This effect is mediated through mitochondrial complex III and involves the inhibition of pro-survival signaling from the integrated stress response (ISR), which typically upregulates anti-oxidative proteins like SLC7A11 and GPX4. The compound was identified as a lead candidate in the laboratory of Wafik S. El-Deiry.