Fig. 10
|
Validation of prodrug activation in cell-based assays. (a) Activation of the TzMe-prodrug of auristatin E (TzMe-AurE) by tert-butyl isonitrile (tBuNC). (b) Viability of MIAPaCa-2 cells in the presence of increasing concentrations of TzMe-AurE, auristatin E, and TzMe-AurE coincubated with tBuNC (600 μM). (c) EC50 values for auristatin E, TzMe-AurE, and TzMe-AurE coincubated with tBuNC. (d) Activation of the TzMe-prodrug of fentanyl (TzMe-Fentanyl) by tBuNC. (e) Dose–response curves for TzMe-fentanyl, fentanyl, and the corresponding samples preincubated with tBuNC (800 μM, 24 h, 37 °C) in a TRUPATH μ-opioid signaling assay. (f) EC50 values for fentanyl, TzMe-Fentanyl, and TzMe-fentanyl preincubated with tBuNC. |