Fig. 5. Screening and identifying Mi-2β inhibitors.
a Schematic representing in vitro screen assay for testing Mi-2β chromatin modulatory activity using FRET-based nucleosome repositioning assay. b The chemical structure of Z36-MP5. c Orientation of Z36-MP5 to homologized Mi-2β. Z36-MP5 was docked into the ATP-binding pocket of homologized Mi-2β. The methyl group of Z36-MP5 extended to a solvent-exposed channel lined with the side chains of Tyr729, Leu755, Met966, and Ile1163, with generating H-bonds via the O atom of keto group with His727, O atom of amide group with Gly756, and protonated N atom of imidazole group with Asp873. The atoms of Z36-MP5 were colored as follows: carbon pink, oxygen red, nitrogen blue, and hydrogen white. The H-bonds between Z36-MP5 and homologized Mi-2β were shown as light-yellow dashed lines. d The inhibitory activity of Z36-MP5 for Mi-2β chromatin modulatory activity, measured as fold change of Mi-2β activity treated with control vehicle (n = 3). e The inhibitory activity of Z36-MP5 with IC50 values against Mi-2β at different ATP concentrations (n = 3). f The expression of Cxcl9 and Cxcl10 mRNA in B16F10 cells treated with Z36-MP5 as indicated concentration for 24 h was determined with RT-qPCR assay (n = 3). f Values represent mean ± SD. The unpaired, two tailed t-test. Source data are provided as a Source Data file.