Extended Data Fig. 5: Comparison of iKeap1 with the previously identified displacer C17.

a, Crystal structure (PDB ID: 5FNQ)⁹ of KEAP1 with its ligand removed, the structure used for the primary virtual screening procedure. b, Crystal structure of KEAP1 (PDB ID: 4IQK) with ligand C17 (Supplementary Table 1), the chemical structure of which is shown in d. c, d, iKeap1, the best displacer of the NFR2 peptide (c), is similar to compound C17, which has previously been identified by experimental methods (d). Although iKeap1 and C17 look similar, they differ in a number of aspects in their core scaffold (thus, analogues of the two compounds cover distinct chemical spaces, assuming that the analogues retain the core scaffold of the parent compound). This similarity, as well as the fact that the predicted docking positions (Fig. 3a) of both ligands (b) are nearly identical, is additional evidence that iKeap1 is binding at the predicted site.