ML385
ML385 is a novel and specific nuclear factor erythroid 2-related factor 2 (NRF2) inhibitor with an IC50 of 1.9 μM [1].
NRF2, a redox sensitive basic leucine zipper (bZIP) transcription factor, has emerged as the “master regulator” of cell survival through coordinated induction of cytoprotective antioxidant genes, phase-II detoxification enzymes, multidrug transporters, and central metabolic pathways. Gain-of-function mutations in NRF2 are common in non-small cell lung cancer (NSCLC), associated with therapeutic resistance [1].
In A549 cells, ML385 treatment at concentrations of 0 ~ 5 μM for 72 h dose-dependently reduced the expression levels of NRF2 and its target genes. At the concentration of 5 μM, a time-dependent decrease in NRF2 signaling could be observed in ML385-treated A549 cells, with the maximum decline at 72 h [1].
In mouse models of human NSCLC, single agent Carboplatin (5 mg/kg, q.d., i.p.) or ML385 (30 mg/kg, q.d., i.p.)-treated groups had 42% and 57% of their pretreatment lung volume at 3 weeks, respectively, while the antitumor and anti-metastatic effect of Carboplatin and ML385 combination treatment was significantly obvious with 74% lung volume retention at 3 weeks [1].
Reference:
[1]. Singh A, Venkannagari S, Oh K H, et al. Small Molecule Inhibitor of NRF2 Selectively Intervenes Therapeutic Resistance in KEAP1-Deficient NSCLC Tumors. ACS Chemical Biology, 2016, 11(11): 3214-3225.
- 1. Jinglei Liu, Yuhan Zhang, et al. "Taurodeoxycholic acid alleviates diquat-induced intestinal barrier function injury in mice through the upregulation of Nrf2-mediated signaling pathway." Animal Diseases. 27 September 2024.
- 2. Xin Deng, Qianfeng Wu, et al. "Eucommia ulmoides Oliv. leaves flavonoids attenuate methylglyoxal‐induced endothelial cell apoptosis in vitro and in vivo by upregulating AKT‐Nrf2 signaling and downregulating oxidative stress." Food Sci Nutr. 2024 Aug 16;12(10):7938-7953 PMID: 39479661
- 3. Zhongcheng Xie, Jiamin Guo, et al. "The suppression of FSP1 expression via NRF2 promotes ferroptosis induced by reactive oxygen species in vascular smooth muscle cells." Process Biochemistry. August 2024.
- 4. Wen Cao, Zengdian Chen, et al. "Honokiol Mitigates Metabolic-Associated Fatty Liver Disease by Regulating Nrf2 and RIPK3 Signaling Pathways." Turk J Gastroenterol. April 5, 2024.
- 5. Xiangyu Zhou, Jincheng Wang, et al."Poria cocos polysaccharides improve alcoholic liver disease by interfering with ferroptosis through NRF2 regulation." Aging (Albany NY). 2024 Mar 20;16(7):6147-6162.
- 6. Zheng Peng, Xiao-Jian Li, et al."Hydrogen exerts neuroprotective effects after subarachnoid hemorrhage by attenuating neuronal ferroptosis and inhibiting neuroinflammation." Free Radic Biol Med. 2024 Mar:215:79-93.
- 7. Hong-Feng Gu, et al. "Artemisinin ameliorates cognitive decline by inhibiting hippocampal neuronal ferroptosis via Nrf2 activation in T2DM mice." Mol Med. 2024 Mar 7;30(1):35. PMID: 38454322
- 8. Luc Rochette, Julie Lorin, et al. "Inhibition Of Foxo Induces Oxidative Stress In Osteosarcoma." Pharmacol Ther. 2013 Dec;140(3):239-57.
- 9. Yang Yang, Lin Yu, et al. "Neuroprotective effects of Lycium barbarum polysaccharide on light-induced oxidative stress and mitochondrial damage via the Nrf2/HO-1 pathway in mouse hippocampal neurons." Int J Biol Macromol. 2023 Aug 14;251:126315. PMID: 37582438
- 10. Bo-Feng Yin, Zhi-Ling Li, et al. "Psoralen alleviates radiation-induced bone injury by rescuing skeletal stem cell stemness through AKT-mediated upregulation of GSK-3β and NRF2." Stem Cell Res Ther. 2022 Jun 7;13(1):241. PMID: 35672836
- 11. Xu-guang Zhang, Ai-xia Liu, et al. "A diarylheptanoid compound from Alpinia officinarum Hance ameliorates high glucose-induced insulin resistance by regulating PI3K/AKT-Nrf2-GSK3β signaling pathways in HepG2 cells." J Ethnopharmacol. 2022 Sep 15;295:115397. PMID: 35605918
- 12. Wen-ying Yang, Xiang Meng, et al. "PRDX6 Alleviates Lipopolysaccharide-induced Inflammation in Human Gingival Fibroblasts by Regulation of NRF2." Research Square. rs-1108989/v1.
- 13. Xin Guo, Pingping Cao, et al. "The neuroprotective effect of phillyrin in intracerebral hemorrhagic mice is produced by activation of the Nrf2 signaling pathway." Eur J Pharmacol. 2021 Oct 15;909:174439. PMID: 34425100
- 14. Jiapeng Hu, Jia Wang, et al."Fructose-1,6-bisphosphatase aggravates oxidative stress-induced apoptosis in asthma by suppressing the Nrf2 pathway." J Cell Mol Med. 2021 Jun;25(11):5001-5014. PMID: 33960626
- 15. Fanrui Zhao, Chunlei Liu, et al. "Walnut-Derived Peptide Activates PINK1 via the NRF2/KEAP1/HO-1 Pathway, Promotes Mitophagy, and Alleviates Learning and Memory Impairments in a Mice Model." J Agric Food Chem. 2021 Mar 10;69(9):2758-2772. PMID: 33591165
- 16. Shen X, Zhao Y, et al. "Upregulation of programmed death ligand 1 by liver kinase B1 and its implication in programmed death 1 blockade therapy in non-small cell lung cancer." Life Sci. 2020;256:117923. PMID: 32522567
- 17. Zheng K, Ma J, et al. "Sulforaphane Inhibits Autophagy and Induces Exosome-Mediated Paracrine Senescence via Regulating mTOR/TFE3." Mol Nutr Food Res. 2020;e1901231. PMID: 32476238
Storage | Store at -20°C |
M.Wt | 511.59 |
Cas No. | 846557-71-9 |
Formula | C29H25N3O4S |
Solubility | insoluble in EtOH; insoluble in H2O; ≥13.33 mg/mL in DMSO |
Chemical Name | 2-(benzo[d][1,3]dioxol-5-yl)-N-(5-methyl-4-(1-(2-methylbenzoyl)indolin-5-yl)thiazol-2-yl)acetamide |
SDF | Download SDF |
Canonical SMILES | O=C(CC1=CC2=C(C=C1)OCO2)NC3=NC(C4=CC=C5N(CCC5=C4)C(C6=C(C=CC=C6)C)=O)=C(S3)C |
Shipping Condition | Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice. |
General tips | We do not recommend long-term storage for the solution, please use it up soon. |
Quality Control & MSDS
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