ML385 engages with NRF2, influencing the DNA binding dynamics of the NRF2-MAFG complex. The compound's addition results in a dose-responsive decrease in anisotropy, with an IC50 of 1.9 μM. ML385 induces a dose-dependent diminution of NRF2 transcriptional activity, reaching a peak inhibitory concentration of 5 μM. In KEAP1 mutant H460 cells, ML385 treatment notably lowers the expression of NRF2 and its associated target genes. It also selectively impairs the colony formation and proliferation of lung cancer cells that exhibit increased NRF2 activity. When used alongside carboplatin, ML385 markedly curtails tumor cell growth, as evidenced by a reduced number of Ki-67 positive cells. Tumor specimens treated with ML385 also display a substantial decrease in NRF2 protein levels and the expression of related target genes[1].
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