ML385

SKU: orb1302920

Description

ML385 is a novel and specific small molecule inhibitor of the NRF2 transcription factor (IC50 = 1.9 µM). It exhibits anti-inflammatory and anti-tumor activities in research models by disrupting the NRF2-mediated antioxidant response pathway, making it a valuable tool for studying oxidative stress in cancer and inflammation.

Research Area

Cell Biology, Immunology & Inflammation

Key Properties

• CAS Number: 846557-71-9
• MW: 511.59
• Purity: >99.99% (May vary between batches)
• Formula: C₂₉H₂₅N₃O₄S
• SMILES: Cc1sc(NC(=O)Cc2ccc3OCOc3c2)nc1-c1ccc2N(CCc2c1)C(=O)c1ccccc1C
• Target: Ferroptosis,Nrf2
• Solubility: 50% PEG300+50% Saline:5 mg/mL (9.77 mM);10% DMSO+40% PEG300+5% Tween 80+45% Saline:3 mg/mL (5.86 mM);DMSO:50 mg/mL (97.73 mM)

Bioactivity

• Target IC50:
  Nrf2:1.9 μM
• In Vivo:
  METHODS: To detect anti-tumor activity in vivo, ML385 (30 mg/kg) and carboplatin (5 mg/kg) were intraperitoneally injected into athymic nude mice harboring human lung cancer tumors A549 or H460 five times a week for three weeks. RESULTS: Treatment with ML385 in combination with carboplatin showed a significant reduction in tumor growth. Although treatment with a single agent resulted in a reduction in tumor growth, the magnitude of these effects was variable between cell lines and did not reach statistical significance. METHODS: To investigate whether Nrf2 modulates acute liver failure (ACLF) through iron death, ML385 (30 mg/kg) was injected intraperitoneally four times per week for four weeks into BALB/c mice constructed in the ACLF model. RESULTS: More severe histopathological lesions were observed in the ML385 group compared to the ACLF group. lipid peroxidation and liver injury were exacerbated by the Nrf2 inhibitor, ML385.
• In Vitro:
  METHODS: Human lung cancer cells A549 were treated with ML385 (0.25-5 μM) for 12-72 h. The expression levels of target genes were detected by RT-qPCR. RESULTS: ML385 dose-dependently and time-dependently decreased the transcriptional activity of NRF2. METHODS: Human lung cancer cells EBC1 were treated with ML385 (1-25 μM) for 48 h, and the expression levels of target proteins were detected by Western Blot. RESULTS: NRF2 expression was inhibited by treatment with 5 μM ML385. When the concentration of ML385 was increased above 5 μM, the NRF2 protein level was restored.
• Cell Research:
  cells are treated with ML385 for 36 h. An equal amount of CellTiter-Blue reagent is added to the wells and the fluorescence is measured after 30 min. The CellTiter-Blue reagent is discarded and the Caspase-Glo (100 μL) reagent is added to the cells and incubated at 37°C for an additional 60-90 min. The resulting luminescence is recorded and the caspase activity is normalized to cell number
• Animal Research:
  Mice tumor xenografts are administered intraperitoneally ML385 (30 mg/kg).

Storage & Handling

• Storage: keep away from moisture | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

Ferroptosis, Inhibitor, ML 385, ML385, ML-385, inhibit, Keap1-Nrf2, Nrf2

Compound Identifiers

PubChem CID

1383822