ML385

ML385 is a specific nuclear factor erythroid 2-related factor 2 (NRF2) inhibitor with an IC₅₀ of 1.9 μM. IC50 & Target:IC50: 1.9 μM (NRF2)^[1] In Vitro:ML385 interacts with NRF2 and affects the DNA binding activity of the NRF2-MAFG protein complex. The addition of ML385 decreases anisotropy in a dose-dependent manner, with an IC₅₀ of 1.9 μM. A dose-dependent reduction in the NRF2 transcriptional activity is observed and the maximum inhibitory concentration is 5 μM by ML385. Treatment with ML385 leads to a significant reduction in NRF2 and downstream target gene expression selectively in KEAP1 mutant H460 cells. ML385 selectively affects the colony forming ability or growth of lung cancer cells with gain of NRF2 function^[1]. 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].