| Identification | Back Directory | [Name]
ML385 | [CAS]
846557-71-9 | [Synonyms]
ML385
CS-2542
ML 385; ML-385
N-[4-[2,3-Dihydro-1-(2-methylbenzoyl)-1H-indol-5-yl]-5-methyl-2-thiazolyl]-1,3-benzodioxole-5-acetamide
1,3-Benzodioxole-5-acetamide, N-[4-[2,3-dihydro-1-(2-methylbenzoyl)-1H-indol-5-yl]-5-methyl-2-thiazolyl]-
2-(1,3-benzodioxol-5-yl)-N-[5-methyl-4-[1-(2-methylbenzoyl)-2,3-dihydroindol-5-yl]-1,3-thiazol-2-yl]acetamide | [Molecular Formula]
C29H25N3O4S | [MDL Number]
MFCD06616124 | [MOL File]
846557-71-9.mol | [Molecular Weight]
511.59 |
| Chemical Properties | Back Directory | [density ]
1.374±0.06 g/cm3(Predicted) | [storage temp. ]
2-8°C | [solubility ]
DMSO:31.4(Max Conc. mg/mL);61.38(Max Conc. mM)
DMF:30.0(Max Conc. mg/mL);58.64(Max Conc. mM)
DMF:PBS (pH 7.2) (1:3):0.25(Max Conc. mg/mL);0.49(Max Conc. mM) | [form ]
powder | [pka]
8.92±0.50(Predicted) | [color ]
white to beige | [InChIKey]
LINHYWKZVCNAMQ-UHFFFAOYSA-N | [SMILES]
O1C2=CC=C(CC(NC3=NC(C4C=CC5=C(C=4)CCN5C(=O)C4=CC=CC=C4C)=C(C)S3)=O)C=C2OC1 |
| Hazard Information | Back Directory | [Uses]
ML385 is a specific nuclear factor erythroid 2-related factor 2 (NRF2) inhibitor with an IC50 of 1.9 μM. | [Biochem/physiol Actions]
ML385 inihbits the activity of the Nrf2 transcription factor by binding to Neh1, a CNC-bZIP domain that allows Nrf2 to heterodimerize with small Maf proteins, blocking NRF2 transcriptional activity. Much research has been done on activating Nrf2 because it induces cytoprotective antioxidant genes. However, some cancer cells may use Nrf2 similarly for their survival. Nrf2 is overexpressed in certain cancers such as non-small cell lung cancer (NSCLC) often due to loss of function mutations in KEAP1, which targets Nrf2 for proteasomal degradation. ML385 was found to have anti-tumor activity with specificity and selectivity for NSCLC cells with KEAP1 mutations. | [in vivo]
ML385 in combination with carboplatin leads to a significant reduction in tumor cell proliferation, demonstrated by fewer Ki-67 positive cells. Tumor samples treated with ML385 show a significant reduction in NRF2 protein level and its downstream target genes[1].
ML385 (intraperitoneal injection; 30 mg/kg; 7 days) weakens the therapeutic effects of MSC-Exo on inflammation-induced astrocytic activation (e.g., reduced reactive astrogliosis, NF-κB deactivation) in mice[3]. | Animal Model: | 8-week-old C57B/6 male mice[3] | | Dosage: | 30 mg/kg; 7 days | | Administration: | Intraperitoneal injection | | Result: | Reversed inhibition of MSC-Exo on hippocampal astrocytic activation in vivo. |
| [storage]
Store at -20°C | [References]
[1] Singh A, et al. Small Molecule Inhibitor of NRF2 Selectively Intervenes Therapeutic Resistance in KEAP1-Deficient NSCLC Tumors. ACS Chem Biol. 2016 Nov 18;11(11):3214-3225. DOI:10.1021/acschembio.6b00651
[2] Xinnong Liu, et al. Isoliquiritigenin ameliorates acute pancreatitis in mice via inhibition of oxidative stress and modulation of the Nrf2/HO-1 pathway. Oxid Med Cell Longev. 20 March 2018.
[3] Xian P, et al. Mesenchymal?stem?cell-derived?exosomes?as a?nanotherapeutic?agent?for?amelioration?of?inflammation-induced?astrocyte?alterations?in?mice.Theranostics.?2019 Aug 14;9(20):5956-5975. DOI:10.7150/thno.33872 |
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