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  • IN BRIEF

Acyl-lysine reader inhibitor blocks AML progression

  1. Sarah Crunkhorn
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The acyl-lysine reader eleven-nineteen-leukemia (ENL) has been identified as a critical dependency in acute myeloid leukemia (AML). Through structure-based optimization of a previously reported chemical probe, Liu et al. develop the potent and orally bioavailable ENL inhibitor TDI-11055. Mechanistically, the compound displaces ENL from chromatin by blocking its YEATS domain interaction with acylated histones, leading to suppression of key oncogenic gene expression programmes. TDI-11055 inhibited the proliferation and colony-forming ability of human leukemia cell lines and primary AML patient cells. Oral treatment with TDI-11055 blocked disease progression in cell line and patient-derived xenograft mouse models of AML.

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Nature Reviews Drug Discovery 21, 798 (2022)

doi: https://doi.org/10.1038/d41573-022-00160-9

References

  1. Liu, Y. et al. Small-molecule inhibition of the acyl-lysine reader ENL as a strategy against acute myeloid leukemia. Cancer Discov. https://doi.org/10.1158/2159-8290.CD-21-1307 (2022)

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