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NEWS ｜ 08 Nov 2024
WIKIMOLE—Liproxstatin-1
By TargetMol
Liproxstatin-1 (Product No. T2376, CAS 50455-15-9) is a potent and selective ferroptosis inhibitor. Liproxstatin-1 can protect cells from ferroptosis induced by ferroptosis inducers such as Erastin and RSL3【1】.
Mechanism of Action
The mechanisms of action of Liproxstatin-1 primarily involve its inhibition of lipid peroxidation. Specifically, it acts through the following mechanisms:
1. Inhibition of Lipid Peroxidation: Liproxstatin-1 effectively blocks lipid peroxidation reactions, thereby reducing the production of reactive oxygen species (ROS) and reactive lipid species, such as lipid peroxides. This process is crucial for protecting cells from oxidative stress damage.
Effects of HK2 cells conditioned medium on fibroblast activation and proliferation. 【2】
2.Intervention in Iron-Dependent Lipid Peroxidation: Liproxstatin-1 specifically inhibits iron-related lipid peroxidation pathways. It achieves this by interfering with iron ion metabolism, thereby reducing the damage of lipid peroxidation to cells and demonstrating neuroprotective properties in cellular models【3】.
3.Regulation of Intracellular Signaling Pathways: By inhibiting lipid peroxidation, Liproxstatin-1 may also indirectly affect signaling pathways related to cell survival and death, such as regulating the AMPK (AMP-activated protein kinase) and mTOR (mechanistic target of rapamycin) pathways, promoting energy metabolism and cell survival【4】.
Application
1. Neuroprotective Effects
Liproxstatin-1 has shown protective effects in models of neurodegenerative diseases. For example, in animal models of Alzheimer’s disease (AD) and Parkinson’s disease (PD), Liproxstatin-1 can reduce oxidative stress-related neuronal damage and improve cognitive function and motor abilities. This has garnered significant attention in the field of neuroscience【5】.
2. Cardiovascular Protection
The potential application of Liproxstatin-1 in cardiovascular diseases is also being explored. Its antioxidant and anti-inflammatory properties may help reduce the risk of cardiovascular conditions such as atherosclerosis and myocardial ischemia. Studies have shown that Liproxstatin-1 can mitigate oxidative damage in myocardial cells and enhance cardiac function【6】.
3. Metabolic Disease Treatment
Due to its inhibitory effect on lipid peroxidation, Liproxstatin-1 is also being investigated for its potential use in metabolic diseases such as diabetes and obesity. By regulating lipid metabolism, Liproxstatin-1 may help improve insulin sensitivity and metabolic status【7】.
4. Cancer Research
Liproxstatin-1’s role in modulating cell proliferation and apoptosis suggests potential applications in cancer research. Studies indicate that Liproxstatin-1 may inhibit lipid peroxidation in cancer cells, reduce their proliferative capacity, and induce apoptosis【8】.
References
[1]Bao C, Liu C, Liu Q, Hua L, Hu J, Li Z, Xu S. Liproxstatin-1 alleviates LPS/IL-13-induced bronchial epithelial cell injury and neutrophilic asthma in mice by inhibiting ferroptosis. Int Immunopharmacol. 2022 Aug;109:108770.
[2]Zhang B, Chen X, Ru F, Gan Y, Li B, Xia W, Dai G, He Y, Chen Z. Liproxstatin-1 attenuates unilateral ureteral obstruction-induced renal fibrosis by inhibiting renal tubular epithelial cells ferroptosis. Cell Death Dis. 2021 Sep 11;12(9):843.
[3]Rui T, Wang H, Li Q, Cheng Y, Gao Y, Fang X, Ma X, Chen G, Gao C, Gu Z, Song S, Zhang J, Wang C, Wang Z, Wang T, Zhang M, Min J, Chen X, Tao L, Wang F, Luo C. Deletion of ferritin H in neurons counteracts the protective effect of melatonin against traumatic brain injury-induced ferroptosis. J Pineal Res. 2021 Mar;70(2):e12704.
[4]Xie Z, Wang X, Luo X, Yan J, Zhang J, Sun R, Luo A, Li S. Activated AMPK mitigates diabetes-related cognitive dysfunction by inhibiting hippocampal ferroptosis. Biochem Pharmacol. 2023 Jan;207:115374.
[5]Costa I, Barbosa DJ, Benfeito S, Silva V, Chavarria D, Borges F, Remião F, Silva R. Molecular mechanisms of ferroptosis and their involvement in brain diseases. Pharmacol Ther. 2023 Apr;244:108373.
[6]Feng Y, Madungwe NB, Imam Aliagan AD, Tombo N, Bopassa JC. Liproxstatin-1 protects the mouse myocardium against ischemia/reperfusion injury by decreasing VDAC1 levels and restoring GPX4 levels. Biochem Biophys Res Commun. 2019 Dec 10;520(3):606-611.
[7]Liu C, Sun W, Zhu T, Shi S, Zhang J, Wang J, Gao F, Ou Q, Jin C, Li J, Xu JY, Zhang J, Tian H, Xu GT, Lu L. Glia maturation factor-β induces ferroptosis by impairing chaperone-mediated autophagic degradation of ACSL4 in early diabetic retinopathy. Redox Biol. 2022 Jun;52:102292.
[8]Lei S, Chen C, Han F, Deng J, Huang D, Qian L, Zhu M, Ma X, Lai M, Xu E, Zhang H. AMER1 deficiency promotes the distant metastasis of colorectal cancer by inhibiting SLC7A11- and FTL-mediated ferroptosis. Cell Rep. 2023 Sep 26;42(9):113110.
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