Data Sheet 1_ALKBH5 inhibitors for cancer therapy: molecular docking, challenges and future prospects.docx

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 33, 25 and 40, 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.