Table 4.
The pharmacophore-derived fit values, docking scores, and the suppression effects of the candidate compounds on EGFR phosphorylation at Y1068.
| NSC Number | 3D-QSAR Fit Value | CFP Fit Value | SBP Fit Value | LibDock Score | Phosphorylation Level (%) | Inhibitory Rate (%) | ||
|---|---|---|---|---|---|---|---|---|
| EGFR p.L858R (PDB: 2ITV) | EGFR p.T790M (PDB: 2JIT) | EGFR p.L858R (PDB: 2ITV) | EGFR p.T790M (PDB: 2JIT) | |||||
| NSC7521 | 6.00 | 3.18 | 2.89 | 2.57 | 124.05 | 122.70 | 75 ± 15 | 25 ± 15 |
| NSC342715 | 6.47 | 3.26 | 2.98 | 2.65 | 123.30 | 119.98 | 37 ± 6 * | 63 ± 6 * |
| NSC622394 | 6.05 | 3.37 | 1.97 | 2.54 | 148.73 | 123.90 | 32 ± 8 * | 68 ± 8 * |
| NSC609077 | 6.22 | 2.79 | 2.77 | 1.68 | 145.57 | 152.88 | 21 ± 6 * | 79 ± 6 * |
| NSC622442 | 6.68 | 3.73 | 3.12 | 2.49 | 129.85 | 124.22 | NA | NA |
| NSC623897 | 6.03 | 3.77 | 2.48 | 3.33 | 117.06 | 116.17 | NA | NA |
* p < 0.05 indicates statistical significance compared with the vehicle control. NA, not available (the corresponding compound was not in the NCI open chemicals repository). NSC Number: National service center number. Abbreviations- 3D-QSAR: 3D quantitative structure-activity relationship, CFP: Common feature pharmacophore, SBP: Structure-based pharmacophore, EGFR: Epidermal growth factor receptor, PDB: Protein data bank.