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Article Abstract
Eleven-nineteen leukemia (ENL) is an epigenetic reader protein that drives oncogenic transcriptional programs in acute myeloid leukemia (AML). AML is one of the deadliest hematopoietic malignancies, with an overall 5-year survival rate of 27%. The epigenetic reader activity of ENL is mediated by its YEATS domain that binds to acetyl and crotonyl marks on histone tails and colocalizes with promoters of actively transcribed genes that are essential for leukemia. Prior to the discovery of , existing inhibitors of ENL YEATS showed potency, but had not shown efficacy in animal models. During the course of the medicinal chemistry campaign described here, we identified ENL YEATS inhibitor that has an improved pharmacokinetic profile and is appropriate for evaluation of the ENL YEATS inhibition mechanism in AML.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11017412 | PMC |
| http://dx.doi.org/10.1021/acsmedchemlett.4c00016 | DOI Listing |
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