ADME attributes of MMAE and DM1
The small-molecule drug portion of an antibody-drug conjugate can be subject to biotransformation, transport, and elimination pathways similar to other small-molecule drugs.
| Attribute | MMAE | DM1 |
|---|---|---|
| Metabolic turnover | Minimal | Extensive |
| P450 involvement | CYP3A4/5 | CYP3A4/5, 2D6 |
| Inhibition potential | IC50 ∼10 µM for CYP3A (tested up to 100 µM) | IC50 ∼2–8 µM for 3A4 and 27 µM for 2D6 (tested up to 50 µM), also 2C8 and 3A5 |
| Induction potential | NA (tested up to 10 µM) | NA (tested up to 1 µM) |
| P-glycoprotein | Substrate, but not inhibitor | Substrate, but not inhibitor |
| Route of excretion | Primarily bile/feces | Primarily bile/feces |
NA, not applicable.