Table 3:
Cross-resistance profile to select ADC payloads in cells expressing P-gp, ABCG2 or MRP1
| Drug | pcDNA | MDR19 | RR | R5 | RR | MRP1 | RR |
|---|---|---|---|---|---|---|---|
| DM1 (nM) | 7.8±1.4 | 410±120 | 52 | 35±4.1 | 4.5 | 9.5±3.7 | 1.2 |
| DM4 (nM) | 0.43±0.075 | 42±20 | 96 | 1.4±0.49 | 3.3 | 0.58±0.37 | 1.3 |
| MMAE (nM) | 0.90±0.23 | 360±110 | 400 | 5.1±1.9 | 5.7 | 1.2±0.80 | 1.3 |
| MMAF (μM) | 0.99±.097 | 2.0±1.7 | 2.0 | 0.99±.097 | 1.0 | 1.0±0.39 | 1.0 |
| Calicheamicin gamma1 | 0.010±0.0042 | 0.73±0.41 | 71 | 0.029±0.0047 | 2.9 | 0.028±0.017 | 2.7 |
| Exatecan (nM) | 0.59±0.19 | 1.4±0.15 | 2.4 | 5.0±0.80 | 8.5 | 1.0±0.19 | 1.8 |
| Deruxtecan (nM) | 0.82±0.18 | 17±1.2 | 20 | 190±29 | 240 | 1.1±0.40 | 1.4 |
| Nemorubicin (nM) | 0.76±0.31 | 1.5±0.15 | 2.0 | 1.1±0.27 | 1.4 | 1.6±0.21 | 2.2 |
| PNU-159682 (pM) | 13±9.6 | 16±3.7 | 1.2 | 13±8.4 | 1.0 | 19±8.6 | 1.4 |
| SJG136 (nM) | 0.098±0.019 | 16±6.2 | 170 | 4.6±0.68 | 47 | 1.2±1.1 | 12 |
| SGD-1882 (nM) | 0.0066±0.0028 | 0.85±0.34 | 130 | 0.22±0.093 | 33 | 0.095±0.036 | 14 |
| SG2057 (nM) | 0.025±0.0087 | 5.7±1.2 | 230 | 0.73±0.34 | 29 | 0.27±0.20 | 11 |
| SG3199 (nM) | 0.045±0.011 | 5.6±1.6 | 120 | 0.90±0.31 | 20 | 0.21±0.026 | 4.6 |
Results are mean GI50 values +/− standard deviation. Relative resistance (RR) value was computed by dividing the GI50 value for the lines expressing the ABC transporters by the empty vector (pcDNA) line. Results are from 3 independent experiments.