Fig. 5

Identification of novel CMTR1 inhibitors: N97911, N169774 and N627666. (A) Ribbon diagram, generated with PyMOL, showing the CMTR1 enzymatic domain in complex with m7G RNA (PDB: 4N49). Three key residues, K203, D207, and E373, along with m7G RNA, are shown and labeled in color. (B) Two-dimensional (2D) representation of the predicted N97911-CMTR1 binding mode, generated using PoseView. Dashed lines indicate hydrogen bonds and green colored lines indicate pi-pi interactions. (C) Association/dissociation binding curves (BLI assay) of one CMTR1 candidate inhibitor (N169774) to the immobilized CMTR1 protein. The green line represents a 20 µM concentration, the orange line represents a 5 µM concentration of the N169774 compound, and the black line represents the vehicle (DMSO) control. (D) Representative images of clonogenic survival in 4T1 cells after treatment with three CMTR1 candidate inhibitors