Two new ALKBH5 inhibitors that block glioblastoma growth by different competitive methods

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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