Synthesis, characterization, molecular docking, and biological evaluation of novel ASK1 inhibitors

Inhibiting apoptosis signal regulated kinase 1 (ASK1) is an attractive strategy for treating diseases such as non-alcoholic steatohepatitis and multiple sclerosis. Here, we report the discovery of a dibromo substituted quinoxaline fragment containing 26e as an effective small-molecule inhibitor of ASK1, with an IC 50 value of 30.17 nM. In addition, the cell survival rate of 26e at different concentrations was greater than 80%, especially at 0.4 μM. Its cell survival rate was significantly higher than GS-4997 , indicating its good safety in normal human liver LO2 cells. The Oil Red O staining experiment showed that 26e decreased the lipid droplets in a dose-dependent manner. Further biochemical analyses revealed that 26e could reduce the content of T-CHO, LDL, and TG in FFA-induced LO2 cells, and had the potential to treat non-alcoholic fatty disease. These findings provide a good choice for the future development of ASK1 inhibitors.

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Synthesis, characterization, molecular docking, and biological evaluation of novel ASK1 inhibitors

Cited by 4 publications

References 21 publications

Prediction of apoptosis signal-regulating kinase 1 (ASK1) inhibition with machine learning methods

Prediction of apoptosis signal-regulating kinase 1 (ASK1) inhibition with machine learning methods

Small-molecule inhibitors targeting apoptosis signal-regulated kinase 1

Synthesis and biological evaluation of quinoxaline derivatives as ASK1 inhibitors

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