Nrf2-IN-1是nuclear factor-erythroid 2-related factor 2 (Nrf2)的抑制剂，用于急性髓系白血病(AML)的研究。
Cas No.:1610022-76-8
Sample solution is provided at 25 µL, 10mM.
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Nrf2-IN-1 is an inhibitor of nuclear factor-erythroid 2-related factor 2 (Nrf2), which is developed for the research of acute myeloid leukemia (AML) [1]. Nrf2-IN-1 inhibited the expression of Nrf2/HO-1/NQO1 pathway-related proteins as well as that of the ferroptosis resistance-related proteins GPX4, SLC7A11, and FTH1[2]. Nrf2-IN-1 has been widely used to regulate oxidative stress in models of myocardial ischemia-reperfusion injury[3].
In vitro, Nrf2-IN-1 treatment for 48 hours significantly inhibited the viability of THP-1 cells, HL-60 cells, and U937 cells, with IC50 values of 5.33µM, 8.94µM, and 8.98µM, respectively[4]. Treatment of microglial cells with 5µM Nrf2-IN-1 for 48 hours significantly inhibited the interaction between Nrf2 and ACOD1 and reduced the expression of ACOD1[5]. Treatment with 10µM Nrf2-IN-1 for 24 hours significantly reduced the expression levels of ADAM8 and Nrf2 in HT22 cells induced by Erastin, promoted the production of reactive oxygen species (ROS), and increased cell death[6].
In vivo, Nrf2-IN-1 treatment via intraperitoneal injection at a dose of 10µmol/kg/day for 7 days counteracted the neuroprotective effect of shRIN1 in the rat model of chronic constriction injury (CCI), significantly increased the Fe2+ level in spinal cord tissue, accompanied by severe mitochondrial damage[7]. Twelve hours before establishing the cecum ligation perforation (CLP) model, intraperitoneal injection of a single dose of Nrf2-IN-1 (10mg/kg) in mice significantly inhibited the protective effect of Klotho on the kidneys and promoted kidney damage[8].
References:
[1] Han Y, Gao X, Wu N, et al. Long noncoding RNA LINC00239 inhibits ferroptosis in colorectal cancer by binding to Keap1 to stabilize Nrf2[J]. Cell death & disease, 2022, 13(8): 742.
[2] Du L, Zhu X, Jiang Z, et al. Resveratrol inhibits ferroptosis in the lung tissues of heat stroke-induced rats via the Nrf2 pathway[J]. BMC Pharmacology and Toxicology, 2024, 25(1): 88.
[3] Li W, Yu W, Xu W, et al. Death-associated protein kinase 1 regulates oxidative stress in cardiac ischemia reperfusion injury[J]. Cells Tissues Organs, 2021, 210(5-6): 380-390.
[4] Zhang J F, Su L, Ye Q, et al. Discovery of a novel Nrf2 inhibitor that induces apoptosis of human acute myeloid leukemia cells[J]. Oncotarget, 2016, 8(5): 7625.
[5] Qian Z, Xia M, Zhao T, et al. ACOD1, rather than itaconate, facilitates p62‐mediated activation of Nrf2 in microglia post spinal cord contusion[J]. Clinical and Translational Medicine, 2024, 14(4): e1661.
[6] Qian Z, Zhang Q, Li P, et al. A disintegrin and metalloproteinase-8 protects against erastin-induced neuronal ferroptosis via activating nrf2/ho-1/fth1 signaling pathway[J]. Molecular Neurobiology, 2024, 61(6): 3490-3502.
[7] Lin X, Li X, Hong S, et al. RIN1 regulates ferroptosis and nociceptive perception via the Nrf2/HO-1 pathway in chronic constriction injury[J]. Cellular Signalling, 2025, 132: 111784.
[8] Zhou P, Zhao C, Chen Y, et al. Klotho activation of Nrf2 inhibits the ferroptosis signaling pathway to ameliorate sepsis-associated acute kidney injury[J]. Translational andrology and urology, 2023, 12(12): 1871.
Nrf2-IN-1是nuclear factor-erythroid 2-related factor 2 (Nrf2)的抑制剂，用于急性髓系白血病(AML)的研究[1]。Nrf2-IN-1抑制Nrf2/HO-1/NQO1通路相关蛋白以及铁死亡抵抗相关蛋白GPX4、SLC7A11和FTH1 的表达[2]。Nrf2-IN-1已被广泛用于调节心肌缺血再灌注损伤模型中的氧化应激[3]。
在体外，Nrf2-IN-1处理48小时显著抑制了THP-1细胞、HL-60细胞和U937细胞的活力，IC50值分别为5.33μM、8.94μM和8.98μM[4]。用5μM的Nrf2-IN-1处理小胶质细胞48小时，显著抑制了Nrf2与 ACOD1之间的相互作用，并降低了ACOD1的表达[5]。用10μM的Nrf2-IN-1处理HT22细胞24小时，显著降低了Erastin诱导的ADAM8和Nrf2表达水平，促进了活性氧(ROS)的产生，并促进了细胞死亡[6]。
在体外，在慢性压迫性损伤大鼠模型中，腹腔注射10μmol/kg/day剂量的Nrf2-IN-1连续7天，抵消了 shRIN1的神经保护作用，显著增加了脊髓组织中的Fe2+水平，并伴有严重的线粒体损伤[7]。在建立盲肠结扎穿孔(CLP)模型前12小时，单次腹腔注射10mg/kg剂量的Nrf2-IN-1，显著抑制了Klotho对小鼠肾脏的保护作用，并促进了肾损伤[8]。
| Cell experiment [1]: | |
Cell lines | THP-1 cells |
Preparation Method | THP-1 cells were cultured in RPMI 1640 medium supplemented with 100U/ml penicillin and 100mg/ml streptomycin in 5% CO2 at 37°C. Cells were placed in a 96 well-plate at a concentration of 1×105 cells per well and were treated with different concentrations of Nrf2-IN-1 (0, 1, 5, 10, and 20µM) for 48h, and then the cell viability was analyzed. |
Reaction Conditions | 0, 1, 5, 10, and 20µM; 48h |
Applications | Nrf2-IN-1 treatment significantly reduced the cell viability of THP-1 cells in a dose-dependent manner. |
| Animal experiment [2]: | |
Animal models | Male adult Sprague-Dawley rats |
Preparation Method | Healthy male adult Sprague-Dawley rats (280-320g) were housed in a specialized animal care facility, in a room with constant temperature (25°C), humidity control, and a 12/12h light/dark cycle with free access to food and water. Aseptic technique was used during the surgical procedure for CCI modeling. Rats were anesthetized with 3% isoflurane in the induction chamber and then maintained with 1-2% isoflurane during surgery. The anesthetized rats were continuously monitored. The hind legs were elevated, shaved, and the surgical site was disinfected with iodophor solution. A 1-1.5cm incision was made approximately 0.5cm below the right posterior superior iliac spine. The muscles were gently separated, and the sciatic nerve was exposed and isolated. Three or four gentle ligations were placed around the nerve trunk using 4-0 chromic catgut ligatures, spaced approximately 1mm apart, ensuring the ligations were tight enough to induce a mild fluttering response in the calf muscle. The muscle layer was closed with a 4-0 suture, and the skin was sutured with a 2-0 suture. The wounds were then disinfected with iodine solution. Rats were closely monitored during recovery from anesthesia and placed in a separate cage with a flat paper pad to ensure safety and prevent asphyxiation of unconscious rats. Rats were intrathecally injected with adeno-associated virus 9 (AAV9) vectors containing shRNA targeting RIN1 (titer 1×108 PFU/ml; 5μl/rat) on the 3rd postoperative day, with a scrambled shRNA used as a control, followed by intraperitoneal injections of Nrf2-IN-1 (10μmol/kg; dissolved in DMSO) for seven consecutive days. The mechanical paw withdrawal threshold (PWT) was recorded in a balanced sequence for both injured and uninjured hind paws. |
Dosage form | 10μmol/kg/day for 7 days; i.p. |
Applications | Nrf2-IN-1 treatment significantly reversed the anti-nociceptive effect of shRIN1 in CCI rats, as the mechanical stimulation threshold and the latency to thermal hyperalgesia of mice were significantly increased. |
References: | |
| Cas No. | 1610022-76-8 | SDF | |
| Canonical SMILES | O=C(NO)C1=CC(C2=CC=C(Cl)C=C2)=NN1CC3=CC=C(C(C)(C)C)C=C3 | ||
| 分子式 | C21H22ClN3O2 | 分子量 | 383.87 |
| 溶解度 | DMSO: 260 mg/mL (677.31 mM) | 储存条件 | Store at -20°C |
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| 1 mM | 2.605 mL | 13.0252 mL | 26.0505 mL |
| 5 mM | 521 μL | 2.605 mL | 5.2101 mL |
| 10 mM | 260.5 μL | 1.3025 mL | 2.605 mL |
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