Determination of total cellular accumulation ratio for KAT6A inhibitors in the unsaturated (Kpunsat) and fully saturated (Kpsat) state in plated ZR75-1 cells
Parameters were obtained by curve fitting of eq. 3 to concentration-dependent Kp measurements ranging from 0.1 to 100 µM total extracellular concentration. Data are expressed as means ± S.E.
| Compound | Kpunsat | Kpsat | Km,app (µM) | R2 | % Saturation a | % Recovery b |
|---|---|---|---|---|---|---|
| WM-8014 | 2.17 ± 0.09 | 31.5 ± 0.7 | 35.2 ± 1.3 | 0.99 | 87 | 102–94 |
| WM-1119 | 1.08 ± 0.07 | 1.60 ± 0.09 | 6.8 ± 2.9 | 0.90 | 93 | 88–92 |
| Compound 1 | 5.4 ± 0.9 | 34.5 ± 1.8 | 17.1 ± 1.9 | 0.99 | 100 | 87–82 |
| Compound 2 | 2.5 ± 0.3 | 31.2 ± 1.4 | 37.2 ± 2.2 | 0.99 | 89 | 115–97 |
| Compound 3 | 1.45 ± 0.09 | 32.9 ± 0.2 | 24.9 ± 0.3 | 0.99 | 97 | 104–91 |
| Compound 4 | 1.3 ± 0.3 | 4.8 ± 1.0 | 18.0 ± 9.8 | 0.94 | 95 | 114–85 |
| Compound 5 | 2.1 ± 0.2 | 10.9 ± 0.3 | 10.7 ± 0.7 | 0.99 | 99 | 102–102 |
| Compound 6 | 1.5 ± 0.2 | 4.0 ± 0.5 | 8.8 ± 4.6 | 0.95 | 101 | 79–85 |
| Compound 7 | 0.56 ± 0.06 | 1.70 ± 0.09 | 9.49 ± 0.12 | 0.97 | 92 | 97–106 |
| Compound 8 | 0.95 ± 0.03 | 8.90 ± 0.05 | 13.0 ± 0.2 | 0.99 | 100 | 97–96 |
| Compound 9 | 1.2 ± 0.3 | 5.3 ± 0.5 | 7.8 ± 2.0 | 0.97 | 103 | 97–76 |
| Compound 10 | 0.49 ± 0.02 | 1.29 ± 0.04 | 11.2 ± 1.2 | 0.99 | 99 | 92–78 |
↵a Percent saturation relates to highest concentration tested, i.e., 100 μM (total). Values were calculated according to eq. 4.
↵b Compound recovery from cell and medium after the experiment (t = 45 min) related to t = 0 min, from lowest and highest initial concentration used (0.1–100 μM). Values were calculated according to eq. 2.