Figure 9.
Structure of quinolinone-based inhibitors and their interaction with IDH1R132H. (A) Structure of preclinical and clinical mIDH1-selective inhibitors with a 1H-quinolin-2-one backbone (indicated in blue) [83,84]. (B) Scheme illustrating inhibitor-protein interactions in the crystal structures of compound 4 (top, PDB: 6O2Y) and FT-2102 (bottom, PDB: 6U4J) in complex with IDH1R132H. Amino acid residues that directly interact with the inhibitors are shown in orange circles, with dotted lines indicating the formation of hydrogen bonds. In addition, key hydrophobic interactions of the inhibitors with the protein are indicated in turquoise. (C) Structure of radiolabeled mIDH inhibitors, with the radiolabels indicated in red [85].