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].
ML385 细胞实验
Cell Line
Concentration
Treated Time
Description
References
KYSE150 cells
5 μM
48 h
ML385 further elevated irradiation-induced ROS, enhancing the irradiation-mediated reduction in cell viability.
Cell Death Dis. 2024 Nov 5;15(11):793.
KYSE450 cells
5 μM
48 h
Inhibition of NRF2 by ML385 caused a substantial increase in ROS levels and a significant reduction in cell viability.
Cell Death Dis. 2024 Nov 5;15(11):793.
N2A cells
5µM
Used to investigate the role of the Nrf2 pathway in neuronal itaconate-induced IL-10 expression; results showed that ML385 inhibited 4-OI-induced IL-10 release
Front Immunol. 2022 Oct 13;13:1012442.
BV2 cells
2µM
Used to investigate the role of the Nrf2 pathway in itaconate-induced IL-10 expression; results showed that ML385 inhibited 4-OI-induced IL-10 release
Front Immunol. 2022 Oct 13;13:1012442.
MDA-MB-436 cells
5 μM
Inhibited Nrf2 expression, downregulated HBXIP and NQO1 protein expression.
NPJ Breast Cancer. 2022 Jan 13;8(1):7.
MG-63 cells
2 µM
2 and 4 h
ML385 significantly increased ROS production in MG-63 cells, indicating that Nrf-2 activation is closely related to and negatively regulates ROS generation.
Int J Nanomedicine. 2018 May 17;13:2907-2919.
rat nucleus pulposus cells (NPCs)
5 μM
To investigate the role of ML385 in inhibiting KGN-mediated antioxidant functions, results showed that ML385 suppressed the expression of antioxidant enzymes in KGN-treated NPCs and led to ECM metabolic imbalance.
J Orthop Translat. 2023 Jul 31;42:15-30.
ML385 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Nude mice
KYSE150 cell xenograft model
30 mg/kg
5 times per week for 3 weeks
ML385 significantly suppressed ΔNp63α-mediated tumor growth, indicating that NRF2 inhibition can counteract ΔNp63α-mediated radioresistance.
Cell Death Dis. 2024 Nov 5;15(11):793.
Mice
Subarachnoid hemorrhage model
Intraperitoneal injection
30 mg/kg
Single injection, lasting 30 minutes
ML385 blocked the Keap1/Nrf2 signaling pathway, inhibiting the antioxidant effects of EDB and EDA.
Front Pharmacol. 2024 May 30;15:1342226
Mice
Middle cerebral artery occlusion model
Intraperitoneal injection
30 mg/kg
Once daily for 7 days
To evaluate the effect of ML385 on the Nrf2/HO-1 signaling pathway, ML385 treatment reversed the influence of curcumol on microglial polarization
Cell Death Discov. 2024 Jun 24;10(1):300.
BALB/c mice
LPS-induced sickness behavior model
Intraperitoneal injection
30 mg/kg
Single injection, lasting 24 hours
To evaluate the effect of ML385 on the protective effects of DMF, results showed that ML385 reversed the protective effects of DMF on LPS-induced sickness behavior.
Front Immunol. 2021 Nov 10;12:737065
ML385 动物研究
Animal study
Administered via intraperitoneal injection at a dosage of 30 mg/kg for a period of 7 days, ML385 diminishes the therapeutic impact of MSC-Exo on inflammation-provoked activation of astrocytes in mice and lessens reactive astrogliosis as well as the deactivation of NF-κB[2].
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