Small proteins with a big job: An EMBOW-derived microprotein targets WDR5-MLL1 and suppresses transcription in leukemia.

Baillie HL., Milne TA.

In this issue of Cell Chemical Biology, Zhang et al.1 report the identification of a high-affinity EMBOW-derived inhibitor of WDR5, Ac7, which demonstrates in-cell target engagement and in vivo antileukemic efficacy. The microprotein-inspired inhibitor potently blocks the WDR5-MLL1 interaction, suppressing H3K4 methylation and transcription of target genes in mixed lineage leukemia (MLL)-rearranged leukemia.

DOI

10.1016/j.chembiol.2025.10.010

Type

Journal article

Publication Date

2025-11-20T00:00:00+00:00

Volume

32

Pages

1305 - 1307

Total pages

2

Keywords

Myeloid-Lymphoid Leukemia Protein, Histone-Lysine N-Methyltransferase, Humans, Leukemia, Intracellular Signaling Peptides and Proteins, Transcription, Genetic, Animals, Antineoplastic Agents

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