Table 2 Values of the different physicochemical parameters comparing the Lipinski rule, in conjunction with the estimation of the lipophilicity and solubility of the different payloads linked to the ADCs
ADC | Payload | Linker | DAR | Date FDA | Lipinski | Solubility | Lipophilicity | AB-MPS | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
MW < 500 | MLOGP ≤ 4.15 | N or O < 10 | NH or OH ≤ 5 | Log S average | Log P average ≤ 5 | cLog D (ChEMBL) | ||||||
Belantamab mafodotin* | MMAF/Auristatin | No cleavable | 4 | 2020 | 1046.32 | − 2.80 | 14 | 5 | − 6.25 | 2.25 | – | – |
Brentuximab vedotin | MMAF/Auristatin | Cleavable enz | 4 | 2011 | 717.98 | 0.69 | 8 | 4 | − 6.20 | 3.47 | 2.01 | 30.99 |
Enfortumab vedotin | MMAF/Auristatin | Cleavable enz | 3.8 | 2019 | 717.98 | 0.69 | 8 | 4 | − 6.20 | 3.47 | 2.01 | 30.99 |
Gemtuzumab ozogamicin | Ozogamicin/Calicheamicin | Cleavable pH | 2–3 | 2000 and 2017 | 1368.35 | − 2.06 | 23 | 8 | − 7.88 | 2.89 | 3.11 | 31.11 |
Inotuzumab ozogamicin | Ozogamicin/Calicheamicin | Cleavable pH | 6 | 2017 | 1368.35 | − 2.06 | 23 | 8 | − 7.88 | 2.89 | 3.11 | 31.11 |
Loncastuximab tesirine | SG3199/PBD dimer | Cleavable enz | 2.3 | 2021 | 725.79 | 2.02 | 9 | 1 | − 7.84 | 4.55 | 4.1 | 36.1 |
Mirvetuximab soravtansine | Maytansinoid DM4 | Cleavable | 3.5 | 2022 | 780.37 | 2.21 | 10 | 2 | − 6.49 | 3.51 | 4.47 | 17.47 |
Polatuzumab vedotin | MMAE/Auristatin | Cleavable enz | 3.5 | 2019 | 717.98 | 0.69 | 8 | 4 | − 6.20 | 3.47 | 2.01 | 30.99 |
Sacituzumab govitecan | SN-38 | Cleavable pH | 7.6 | 2020 | 392.40 | 1.55 | 6 | 2 | − 4.63 | 2.46 | 1.87 | 19.13 |
Tisotumab vedotin | MMAE/Auristatin | Cleavable enz | 4 | 2021 | 717.98 | 0.69 | 8 | 4 | − 6.20 | 3.47 | 2.01 | 30.99 |
Trastuzumab deruxtecan | DXd | Cleavable enz | 8 | 2019 | 493.48 | 1.26 | 8 | 3 | − 4.21 | 1.98 | 0.51 | 22.49 |
Trastuzumab emtansine* | DM1/Auristatin | No cleavable | 3.5 | 2013 | 1103.71 | − 2.07 | 16 | 5 | − 6.17 | 1.82 | – | – |