Discovery of two novel ALKBH5 selective inhibitors that exhibit uncompetitive or competitive type and suppress the growth activity of glioblastoma multiforme

Two novel inhibitors, Ena15 and Ena21, were identified that may target the RNA demethylation enzyme ALKBH5.

• Ena15 and Ena21 showed either uncompetitive or competitive inhibition for 2-oxoglutarate.
• Ena21 had minimal effect on another enzyme, FTO, while Ena15 increased its demethylase activity.
• Knockdown of ALKBH5 or treatment with either inhibitor reduced proliferation in glioblastoma multiforme-derived cell lines.
• These treatments led to a decrease in the cell population during the synthesis phase of the cell cycle.
• Increased levels of mA RNA and stabilization of FOXM1 mRNA were observed following these interventions.

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