Fig. 6.
A series of compounds with disparate binding modes. (A) A series of compounds were chosen that share a central urea and common methylphenylpyrimidine on one end (gray box). Different substituents on the other side of the urea cause changes in binding mode. The PathHunter IC50 values are given below the compounds. For compounds 5 and 7, the TrkB value was not measured. (B) Structures of compounds 5, 6, and 7 are shown on the Left. On the Top Right is compound 5 bound in mode 2. In the Middle is compound 6 in mode 3. On the Bottom is compound 7 bound in the active site. In all three structures, the kinase is in green and the DFG motif is in magenta sticks. The JM is in cyan. On the Right are the corresponding SPR traces of the compounds with either full intracellular region (construct 1) or the isolated kinase.