The histone acetyltransferases (HATs) in mammals include GCN5 N-acetyltransferases, the MOZ, YBF2, SAS2, and TIP60 proteins, and the orphan HATs. The males absent on the first (MOF) is mainly related to acetylation of histone H4 Lys16 and has influence on downstream genes expression. However, the only inhibitor MG149 presented low activity against MOF. Besides, there was no high throughput screening platform on MOF, which limited the inhibitor discovery and functional study. In our study, we set up a high throughput screening platform based on amplified luminescent proximity homogeneous assay (ALPHA), which led us to a moderate inhibitor DC_M01. By chemical modification, we found DC_M01_7, which was the analog of DC_M01 with an IC₅₀ value of 6 μM. DC_M01_7 significantly inhibited HCT116 cells proliferation and could also inhibit histone 4 lysine 16 acetylation in HCT116 cells. To sum up, our work will probably assist the further development of more potent MOF inhibitors and the functional study of hMOF.

哺乳动物中的组蛋白乙酰基转移酶（HAT）包括GCN5 N-乙酰基转移酶，MOZ，YBF2，SAS2和TIP60蛋白以及孤立的HAT。缺少第一个（MOF）的雄性主要与组蛋白H4 Lys16的乙酰化有关，并且对下游基因表达有影响。但是，唯一的抑制剂MG149对MOF的活性较低。此外，MOF上没有高通量筛选平台，这限制了抑制剂的发现和功能研究。在我们的研究中，我们建立了一个基于扩增发光邻近均相分析（ALPHA）的高通量筛选平台，这使我们得到了中等抑制剂DC_M01。通过化学修饰，我们找到了DC_M01_7，它是具有IC ₅₀的DC_M01的类似物值为6μM。DC_M01_7显着抑制HCT116细胞的增殖，还可以抑制HCT116细胞中的组蛋白4赖氨酸16乙酰化。综上所述，我们的工作可能会有助于更有效的MOF抑制剂的进一步开发和hMOF的功能研究。