N-(tert-Butyl)-1'H-spiro[piperidine-4,2'-quinoxalin]-3'-amine

Liproxstatin-1 analog is an analog of the ferroptosis inhibitor liproxstatin-1.

Whether spinal cord ferroptosis contributes to morphine tolerance was investigated. C57BL/6 mice were continuously subcutaneously injected with morphine, with or without the ferroptosis inhibitor liproxstatin-1. Chronic morphine exposure led to morphine antinociception tolerance, accompanied by loss of spinal cord neurons, increase in the levels of iron, malondialdehyde, and reactive oxygen species, and decreases in the levels of superoxide dismutase. Additionally, inflammatory response and mitochondrial shrinkage, processes that are involved in ferroptosis, were observed. 10 mg/kg of liproxstatin-1 could alleviate iron overload by balancing transferrin receptor protein 1/ferroportin expression and attenuate morphine tolerance by increasing glutathione peroxidase 4 levels, while reducing the levels of malondialdehyde and reactive oxygen species. It also downregulated the expression of extracellularly regulated protein kinases that had been induced by chronic morphine exposure. These results indicate that spinal cord ferroptosis contributes to morphine tolerance, while liproxstatin-1 attenuates the development of morphine tolerance._x000D_ _x000D_ Reference: ACS Chem Neurosci. 2019 Dec 18;10(12):4824-4833. https://pubs.acs.org/doi/10.1021/acschemneuro.9b00539

Liproxstatin-1 is a potent ferroptosis inhibitor and inhibits ferroptotic cell death (IC50=22 nM).