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. 2017 Nov;45(11):1120–1132. doi: 10.1124/dmd.117.076414

TABLE 2 .

A list of parameters used to build the cellular disposition model for MMAE and T-vc-MMAE

Parameters Description Units Value (CV%) Source
Inline graphic, Inline graphic Volume of the media compartment for MMAE and T-vc-MMAE model, respectively ml 3, 10 Fixed
Inline graphic Scaling factor to convert the number of molecules to nanomoles. Unitless Inline graphic Fixed
Inline graphic, Inline graphic Volume of each cell pl 3.12, 8.14 Fixed
Inline graphic, Inline graphic Doubling time associated with each cell line H 40.1, 33.6 Singh et al. (2016b)
Inline graphic Total concentration of intracellular tubulin nM 65 Shah et al. (2012)
Inline graphic, Inline graphic Second-order association and first-order dissociation rates of MMAE binding to tubulin 1/nM/h, 1/h 0.0183, 0.545 Shah et al. (2012)
Inline graphic, Inline graphic Second-order association and first-order dissociation rates of T-vc-MMAE binding to HER2 1/nM/h, 1/h 0.37, 0.014 Maass et al. (2016)
Inline graphic First-order net antibody-HER2-complex internalization rate 1/h 0.11 Maass et al. (2016)
Inline graphic First-order nonspecific deconjugation rate of MMAE from ADC 1/h ∼0 Estimated to be very low value
Inline graphic Average drug/antibody ratio for the formulation of T-vc-MMAE Unitless 4.5 Measured in-house
Inline graphic Number of HER2 receptors on N87 and GFP-MCF7 cells, respectively Unitless 950,000, 52,000 Measured in-house
Inline graphic,Inline graphic First-order rate of protease-induced intracellular ADC degradation and MMAE release 1/h 0.353 (9%), 0.03 Estimated, Maass et al. (2016)
Inline graphic Average first-order influx rate constant for MMAE from extracellular space to intracellular space for N87 and MCF7 cells. 1/h 8.33 (8.5%) Estimated
Inline graphic Average first-order efflux rate constants for MMAE from intracellular space to extracellular space for N87 and MCF7 cells. 1/h 0.199 (14%) Estimated