Fig 1: DEL screening identifies BBC1115 as a candidate BET inhibitor(A) Schematic diagram for rational design of DEL screening for BET-inhibitor compounds. (B) TR-FRET assay to determine the binding affinity of 20 candidate BET inhibitors of the BD1s and BD2s from BRD2, BRD3, and BRD4. (C) Western blot analysis of whole-cell lysates from murine AML (MLL-AF9; NrasG12D) cells treated for 6 h with DMSO, RVX-208 (1 µM), OTX-015 (1 µM), or candidate BET inhibitors (10 µM). (D) Real-time quantitative reverse transcription PCR (RT-qPCR) of Myc mRNA in murine AML after 6 h treatment with the indicated BET inhibitors or DMSO. The results were normalized against Tbp. Mean ± SEM are shown. (E) Western blot analysis of whole-cell lysates from various human leukemia-derived cell lines treated for 48 h with DMSO, RVX-208, OTX-015, or BBC1115. (F) RT-qPCR analysis of Hexim1 in murine AML after 6 h treatment with indicated drugs. (G) RVX-208, OTX-015, and BBC1115 chemical structures. See also Figure S1.