Figure 10.

(A) Structure of tetrahydropyrazolopyridine-based inhibitors and their interaction with IDH1_R132H. Structure of preclinical mIDH1-selective inhibitors with a tetrahydropyrazolopyridine backbone (indicated in blue) [86]. (B) Scheme illustrating inhibitor-protein interactions in the crystal structure of GSK321 in complex with IDH1_R132H (PDB: 5DE1). Amino acid residues that directly interact with the inhibitor are shown in orange circles, with dotted lines indicating the formation of hydrogen bonds. In addition, key hydrophobic interactions of the inhibitor with the protein are indicated in turquoise.