{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T11:07:55Z","timestamp":1790334475405,"version":"4.1.0"},"reference-count":81,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T00:00:00Z","timestamp":1790294400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>\n                    N\n                    <jats:sup>6<\/jats:sup>\n                    -Methyladenosine (m\n                    <jats:sup>6<\/jats:sup>\n                    A), the most abundant internal modification of eukaryotic mRNA, is dynamically reversed by the Fe\n                    <jats:sup>II<\/jats:sup>\n                    \/\u03b1-ketoglutarate-dependent dioxygenase ALKBH5, a key m\n                    <jats:sup>6<\/jats:sup>\n                    A \u201ceraser\u201d that regulates target mRNA fate through demethylation. ALKBH5 is aberrantly overexpressed in acute myeloid leukemia, glioblastoma, breast cancer and other malignancies, where it sustains oncogenic programs, establishing it as a promising epitranscriptomic drug target. At present, ALKBH5 inhibitor development lags behind that of FTO, with selective agents only recently emerging through covalent inhibitors such as compound\n                    <jats:bold>33<\/jats:bold>\n                    ,\n                    <jats:bold>25<\/jats:bold>\n                    and\n                    <jats:bold>40<\/jats:bold>\n                    , though no clinically available ALKBH5-targeted drug yet exists. This review summarizes the biological functions, structural features, and molecular docking between reported inhibitors and target proteins of ALKBH5. Current challenges, including selectivity over homologous dioxygenases, structural optimization and resistance mechanisms, are critically discussed, alongside future perspectives on structure-guided design, combination regimens and clinical translation. This review provides a medicinal chemistry framework to accelerate the discovery of potent and selective ALKBH5 inhibitors for precision cancer therapy.\n                  <\/jats:p>","DOI":"10.3389\/fphar.2026.1946973","type":"journal-article","created":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T10:26:27Z","timestamp":1790331987000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["ALKBH5 inhibitors for cancer therapy: molecular docking, challenges and future prospects"],"prefix":"10.3389","volume":"17","author":[{"given":"Chen","family":"Deng","sequence":"first","affiliation":[{"name":"Norman Bethune International Institute of Canada for Healthcare Innovation","place":["Toronto, ON, Canada"]},{"name":"International Institute of Synthetic Biology - Canada","place":["Toronto, ON, Canada"]},{"name":"Guangxi Clinical Medical Research Center of Hepatobiliary Disease","place":["Baise, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hai","family":"Xu","sequence":"additional","affiliation":[{"name":"Norman Bethune International Institute of Canada for Healthcare Innovation","place":["Toronto, ON, Canada"]},{"name":"International Institute of Synthetic Biology - 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