Incorporation of Payload Binding to Target

Payload binding to target can be incorporated in the model as shown in Eq. (9), where k _on^{PL ‐ Target} is the association rate constant for payload (DM1) binding to its intracellular target (tubulin) in (#/cell)⁻¹ h⁻¹, k _off^{PL ‐ Target} is the dissociation rate constant in h⁻¹, T is the amount of target (tubulin) in cells in #/cell, and Q is the number of drug-target complexes per cell.

For these analyses, we used the following previously reported values (8, 27): K _D^{PL ‐ Target}(=k _on^{PL ‐ Target}/k _off^{PL ‐ Target}) of 930 nM, k _on^{PL ‐ Target} of 0.44 M⁻¹ h⁻¹, and T of 65 nM. To convert the amount of payload drug (D) from #/cell to an intracellular concentration, we assumed the cell volume was 1000 μm³.