ALKBH1-In-1

ALKBH1-In-1 is a selective small-molecule inhibitor of AlkB homolog 1 (ALKBH1), an Fe(II)/α-ketoglutarate–dependent dioxygenase. ALKBH1 functions as an RNA-modifying enzyme that regulates tRNA decoding, codon-biased translation, and mitochondrial fitness. In the context of acute myeloid leukemia (AML), ALKBH1 expression is linked to RNA-processing and translation-centered transcriptional programs, supporting leukemia-initiating cell self-renewal and resistance to venetoclax. ALKBH1-In-1 has demonstrated pre-clinical activity by inducing dose-dependent apoptosis and inhibiting cell growth in various AML models, including those with venetoclax resistance, by disrupting mitochondrial homeostasis and bioenergetic programs.