Liproxstatin-1 acts as a powerful inhibitor of ferroptosis, blocking ferroptotic cell death with an IC50 value of 22 nM[1].
体内研究
Liproxstatin-1 (10 mg/kg, i.p.) inhibits ferroptosis in human cells, Gpx4/kidney, and in a model of ischemia/reperfusion-induced tissue injury[1].
体外研究
Liproxstatin-1 exhibits antiferroptotic effects, with an IC50 value of around 38 nM in mouse embryonic fibroblasts[2].
作用机制
Liproxstatin-1 is a spiroquinoxalinamine derivative that suppresses ferroptosis via lipid peroxide scavenging in vivo. The benzene ring and higher HOMO energy have beneficial effect on increasing the lipid radical scavenging activity.
Liproxstatin-1 细胞实验
Cell Line
Concentration
Treated Time
Description
References
MOLP-8
1 µM
10 h
Inhibited ferroptosis in LILRB1-KD MM cells
Nat Commun. 2024 Jul 9;15(1):5767.
ARP-1
1 µM
10 h
Inhibited ferroptosis in LILRB1-KD MM cells
Nat Commun. 2024 Jul 9;15(1):5767.
MDA-LM2
1 µM
1 hour
To evaluate the inhibitory effect of Liproxstatin-1 on TBHP-induced cell death
Nat Cancer. 2023 May;4(5):682-698.
NCI-H522 cells
0.25 μM
3 days
Liproxstatin-1, as a selective ferroptosis inhibitor, was used to rescue cell death induced by cytotoxic analogs. All analogs of the amide series showed significant cytotoxicity in NCI-H522 cells, which was completely rescued in the presence of Liproxstatin-1.
J Med Chem. 2022 Sep 8;65(17):11788-11817.
HIEC (human normal small intestinal epithelial cell line)
1 μM
24 h
Liproxstatin-1 significantly reversed hypoxia-induced cell death in HIEC, indicating that the mode of cell death induced by hypoxia was predominantly ferroptosis.
flower exosome-like nanoparticles attenuates gastric and small intestinal mucosal ferroptosis caused by hypoxia through inhibiting HIF-1α- and HIF-2α-mediated lipid peroxidation. J Nanobiotechnology.
NGEC (human normal gastric epithelial cell line)
1 μM
24 h
Liproxstatin-1 significantly reversed hypoxia-induced cell death in NGEC, indicating that the mode of cell death induced by hypoxia was predominantly ferroptosis.
flower exosome-like nanoparticles attenuates gastric and small intestinal mucosal ferroptosis caused by hypoxia through inhibiting HIF-1α- and HIF-2α-mediated lipid peroxidation. J Nanobiotechnology.
A375P cells
2 μM
24 h
To measure lipid peroxidation, results showed that Liproxstatin-1 significantly reversed DC661-induced lipid peroxidation
J Clin Invest. 2023 Apr 17;133(8):e164596.
A375P cells
2 μM
24 h
To measure lipid peroxidation, Liproxstatin-1 significantly reversed DC661-induced lipid peroxidation
J Clin Invest. 2023 Apr 17;133(8):e164596.
HK-2 cells
0.5 µM
24 h
To investigate the effect of Liproxstatin-1 on oxalate-induced ferroptosis in HK-2 cells, results showed that Liproxstatin-1 inhibited oxalate-induced ferroptosis.
J Transl Med. 2024 Jan 2;22(1):9.
human melanoma cells
1 μM
24 h
To test the effect of Liproxstatin-1 on ferroptosis in melanoma cells, the results showed that Liproxstatin-1 blocked the effect of Erastin on cell count reduction.
Nature. 2020 Sep;585(7823):113-118.
Liproxstatin-1 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Mice
MM model
Intraperitoneal injection
15 mg/kg
Daily
Reversed the inhibition of MM progression induced by LILRB1 deficiency
Nat Commun. 2024 Jul 9;15(1):5767.
Mice
Kidney stone mouse model
Injection
10 mg/kg
15 days
To investigate the protective effect of Liproxstatin-1 on CaOx-induced kidney injury, results showed that Liproxstatin-1 alleviated CaOx-induced kidney injury.
J Transl Med. 2024 Jan 2;22(1):9.
Mice
NSG and C57BL mice
Intraperitoneal injection
20 mg/kg
Daily injections until the end of the experiment
To test the effect of Liproxstatin-1 on the survival of melanoma cells in the blood, the results showed that Liprox pre-treatment significantly increased metastatic disease burden in most efficiently metastasizing melanomas.
Nature. 2020 Sep;585(7823):113-118.
BALB/c nude mice
Footpad implantation nude mouse model
Intraperitoneal injection
10 mg/kg
Once daily for 20 days
Liproxstatin-1, as a ferroptosis inhibitor, was used to study its effect on tumor growth and metastasis. The results showed that Liproxstatin-1 slightly promoted tumor growth but had no significant effect on lymph node metastasis.
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