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UNC669 is a potent and selective small molecule inhibitor for the methyl-lysine (Kme) reading function of L3MBTL1, a member of the malignant brain tumor (MBT) family of chromatin-interacting transcriptional repressors. UNC669 binds L3MBTL1 with a Kd of 5±1 μM (IC₅₀?= 6 ±0.5 μM), exhibiting 5-fold greater affinity than the cognate peptide H4K20Me1, 6-fold selective over its close homologue L3MBTL3 and 10-fold selective over L3MBTL4. The first cocrystal structure of UNC669 bound to L3MBTL1 was determined and provides new insights into binding requirements for further ligand design. UNC669 can serve as a useful chemical tool to interrogate the functions of MBT proteins and probe methyl-lysine reader proteins as a target class.

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How to Use:

• In vitro:? UNC1215 was used at 10-25 μM final concentration in vitro and in cellular assays.
• In vivo:???n/a

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Reference:

1. 1. Herold JM, et al. Small-molecule ligands of methyl-lysine binding proteins. (2011) J Med Chem. 54(7):2504-11.
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