Table I.
Cytotoxic Potencies of Maytansinoids Towards Human Carcinoma Cell Lines in vitro
| Maytansinoid | In vitro IC50 (nM) | ||||
|---|---|---|---|---|---|
| A375 (melanoma) | BJAB (B-cell) | COLO205 (colon) | KB (cervix) | MOLT-4 (T-cell) | |
| Maytansine | 0.05 | 0.03 | 0.08 | 0.05 | 0.09 |
| Lysine-Nε-SPP-DM1 | 10 | 50 | 60 | 10 | >100 |
| Lysine-Nε-SPDB-DM4 | 2 | 7 | 20 | 3 | 16 |
| Lysine-Nε-SMCC-DM1 | 8 | 8 | 17 | 10 | 16 |
| S-methyl-DM1 | 0.02 | 0.01 | 0.03 | 0.02 | 0.03 |
| S-methyl-DM4 | 0.02 | 0.01 | 0.03 | 0.03 | 0.03 |
| S-methyl-DM1 sulfoxide | 9.7 | 7.1 | 17 | 23 | 19 |
| S-methyl-DM1 sulfone | – | 1.7 | 5.9 | 3.5 | – |
| S-methyl-DM4 sulfoxide | 0.55 | 0.55 | 1.3 | 2.0 | 1.9 |
| S-methyl-DM4 sulfone | 0.075 | 0.17 | 0.63 | 0.80 | 1.1 |
All metabolites were chemically synthesized. Cell-killing activities of the metabolites were measured after 5 days using a WST-based cell viability assay. Adapted from (30)