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MS41 is a selective eleven-nineteen leukemia (ENL) PROTAC degrader, with DC50s of 3.50 nM (MV4;11), 2.84 nM (SEMK2), 3.03 nM (Jurkat), and 26.58 nM (KASUMI1), respectively. MS41 effectively inhibits the growth of ENL-dependent leukemia cells, induces G1 cell cycle arrest and increases apoptosis. MS41 reduces the chromatin occupancy of ENL-associated transcription elongation machinery, and suppresses oncogenic gene expression and leukemia progression. Red: ENL ligand (HY-169094). Black: linker (HY-W105744). Blue: VHL ligand (HY-112078)[1]. | [References]
[1] Xue Z, et al. A potent and selective ENL degrader suppresses oncogenic gene expression and leukemia progression. Sci Adv. 2024 Aug 30;10(35):eado1432. DOI:10.1126/sciadv.ado1432 |
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