Fig. 6. R-group optimisation case study. (a) Crystal structure (PDB ID 4X5Z) of the initial complex bound to menin. (b) Structure of two of the most potent optimised compounds (PDB IDs left 5DB2, right 5DB3). The dashed lines represent key interactions. (c) Overlay of the most potent optimised compound (green carbons, PDB ID 5DB3) and several compounds generated by DEVELOP (yellow carbons) that make similar hydrogen bonding interactions (dashed lines).