TABLE 1 .
ADC | Time | PBD-dimer |
Cyclopropyl-thiol |
mAb |
||||||
---|---|---|---|---|---|---|---|---|---|---|
Plasma | Liver | Tumor | Plasma | Liver | Tumor | Plasma | Liver | Tumor | ||
h | nM | nM | nM | nM | nM | nM | nM | nM | nM | |
Cyclobutyl-containing | 24 | 0.43 | 0.26 | 1.03 | NA | NA | NA | 370 | 24.8 | 43.5 |
0.55 | 0.55 | 2.09 | NA | NA | NA | 342 | 19.5 | 25.0 | ||
96 | <LLOQ | <LLOQ | 1.93 | NA | NA | NA | 285 | 20.9 | 25.3 | |
<LLOQ | <LLOQ | 2.05 | NA | NA | NA | 272 | 21.1 | 56.0 | ||
Cyclopropyl-containing | 24 | ND | ND | ND | 0.74 | 1.42 | 7.58 | 294 | 28.4 | 59.4 |
ND | ND | ND | 0.57 | 0.63 | 6.76 | 216 | 18.6 | 27.4 | ||
96 | ND | ND | ND | <LLOQ | <LLOQ | 4.33 | 349 | 23.4 | 23.5 | |
ND | <LLOQ | ND | 0.30 | 0.34 | 4.69 | 331 | 16.6 | 16.6 |
NA, not applicable; LLOQ, lower limit of quantitation, 0.24 nM for both analytes in homogenates (nanomolar concentration in tumor and liver was estimated on the basis of an assumption of tissue density of 1 g/ml).