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• W4224099160 abstract "A group of RNA methylation enzymes is currently of interest as a new target for cancer therapy. Alpha-ketoglutarate-dependent dioxygenase B (AlkB) homolog 5 (ALKBH5) is an N6 -methyladenosine (m6 A) demethylation enzyme, and by high-throughput screening from pure small molecule compounds, we identified two novel inhibitors, Ena15 and Ena21, against it. Each compound showed either uncompetitive or competitive inhibition for 2-oxoglutarate (2OG). In addition, Ena21 had little inhibitory activity for fat mass and obesity-associated protein (FTO), which is another N6 -methyladenosine demethylation enzyme, while Ena15 enhanced the demethylase activity of FTO. The predicted binding poses of both compounds with the crystal structure of ALKBH5 (PDB ID: 4NRO) were comparable with these observations pertaining to the interaction of the 2OG catalytic site in this enzyme kinetics. Furthermore, either knockdown of ALKBH5 or inhibition with Ena15 or Ena21 inhibited cell proliferation of glioblastoma multiforme-derived cell lines, decreased cell population in the synthesis phase of the cell cycle, increased m6 A RNA level, and stabilized FOXM1 mRNA. Based on these results, Ena15 and Ena21 were found to be potential candidates that might help in further research into the biological function of ALKBH5." @default.
• W4224099160 created "2022-04-19" @default.
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• W4224099160 date "2022-04-08" @default.
• W4224099160 modified "2023-10-17" @default.
• W4224099160 title "Discovery of two novel ALKBH5 selective inhibitors that exhibit uncompetitive or competitive type and suppress the growth activity of glioblastoma multiforme" @default.
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• W4224099160 doi "https://doi.org/10.1111/cbdd.14051" @default.
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