Fig. 1

Identification of CP-17 as an inhibitor of IDH2/R140Q. a Structure-based in silico screening of a small molecule library (ChemDiv) for compounds that bind to the allosteric site of IDH2/R140Q identifies a hit compound CP-17 with IC₅₀ of 40.75 nM. HTVS: High-throughput Virtual Screening mode; SP: Standard-Precision mode; XP: Extra-Precision mode. b Structure of CP-17 binding at the allosteric site of IDH2/R140Q. The protein was represented as cartoon (colored in light blue and yellow for each monomer), the carbon atoms of CP-17 as magenta sticks, NADPH and Q140 as green sticks, and the Ca²⁺ as black spheres. c Molecular interactions of CP-17 binding at the IDH2/R140Q dimer interface (light blue and yellow for carbon atoms of adjacent monomer residues). The hydrogen bonds between CP-17 and Q316 residue were labeled with red dotted lines