A concept of efficient parking in smart cities

Discovery of WD Repeat-Containing Protein 5 (WDR5)–MYC Inhibitors Using Fragment-Based Methods and Structure-Based Design

“…Moreover, similar to the effect observed with the previous molecules we demonstrated a functional effect of 3d, 6, 8, and 12 binding to WDR5, as they inhibited the biochemical histone methyltransferase activity of MLL-1 in the full WDR5, RBBP5, ASH2L, and DPY30 (WRAD) complex (Supplemental Table 4). It is known that a functional WRAD MLL complex requires binding of proteins to both the WIN and WBM site of WDR5 [23][24][25] ; this data confirms that disrupting the interaction at the WBM site can inactivate the transferase activity of the complex, presumably by disrupting the interaction of WDR5-RBBP5, thus preventing the assembly of the WRAD complex.…”

“…Compound 5 was synthesized by N-alkylating 2bromo-4-nitro-1H-imidazole 23, and subsequent coupling with vinyl boronic pinacol ester using Suzuki conditions (24). Hydrogenation of the alkene and nitro groups was achieved in the same step (25). Finally, reacting 25 with 17 formed the sulfonamide.…”

“…After purification, 3 mg (0.007 mmol, 1% yield) of the title compound was obtained. 13 C NMR (101 MHz,149.80,138.00,137.78,130.72,130.46,124.92,124.44,112.06,44.51,34.17,25. Table 3 Examples…”