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Overview
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Please contact us at for specific academic pricing.
Background
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].
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