Fig. 1. Chemistry, known menin inhibitors, and overview of the overall workflow. (A) The reaction scheme of the GBB-3CR; (B) previously described highly optimized menin–MLL antagonists; (C) a 384-well destination/reaction plate performed on the 500 nmol scale and charged by an Echo 555; (D) MS analytics of the crude reaction wells; (E) differential scanning fluorimetry (DSF) screening of the crude reaction wells for menin binding; (F) resynthesis of discovered hits on a mmol scale; (G) determination of accurate K_d by microscale thermophoresis (MST); (H) determination of the 3D ligand–receptor interaction by co-crystal structure analysis.