YK01 serves as a BCL6-BTB inhibitor. (IMAGE)
Caption
(A) Homogenous time-resolved fluorescence (HTRF) assay screening schematic. (B) HTRF assay screening compounds. (C) HTRF assay showed that the effect of FX1, BI-3802, and YK01 blocked the interaction between BCL6-BTB and SMRT. (D) Chemical structure of compound FX1, BI-3802, and YK01. (E) Schematic diagram of a luciferase reporter plasmid screening model. GAL4-DBD-BCL6-BTB bound to (GAL4)5-TK-LUC to inhibit fluorescence expression, and the fluorescence value recovered after the substance. (F) FX1, BI-3802, and YK01 inhibited BCL6-BTB-mediated transcriptional repression in luciferase reporter assays. (G) Reporter assays were performed to test the activities of YK01 with different BTB-related proteins (BCL6, Kaiso, and PLZF). (H) SPR sensorgram of YK01 binding to BCL6BTB, with YK01 concentrations and calculated KD for binding shown. (I) C57/BL6 mice were immunized with NP18-CGG and intraperitoneally administered YK01 at a dosage of 50 mg/kg/d for 12 days to further detect whether YK01 could inhibit the transcriptional inhibitory function of BCL6 in vivo. (J) Flow cytometry detection of splenic GC-B cells (B220+GL7+FAS+) percentage and statistical graph of the total number of B cells or the percentage of GC-B cells in the mouse spleen. **P < 0.01 and ****P < 0.0001.
Credit
Min Wu, Lin Zhang, Weikai Guo, Shiyi Lv, Wangrui Jin, Shuangshuang Zhu, Huang Chen, Shuyi Jian, Layang Liu, Yajing Xing, Shihong Peng, Mingyao Liu, Yihua Chen, Zhengfang Yi
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