Table 1. Parameters of Kinetic Interaction with VEGFR2a.
compd | Kd (nmol/L) | kon (s–1 × M–1) | koff (s–1) | residence time (min) |
---|---|---|---|---|
lenvatinib | 2.1 ± 0.1 | 4.8 × 105 ± 1.4 × 104 | 9.9 × 10–4 ± 9.0 × 10–5 | 17 ± 2 |
sorafenib | 33 ± 2.6 | 7.9 × 103 ± 1.5 × 102 | 2.6 × 10–4 ± 2.5 × 10–5 | 64 ± 6 |
sunitinib | 30 ± 1.7 | >1.9 × 105 | >57 × 10–4 | <2.9 |
Kd = equilibrium dissociation constant, calculated by using the Cheng–Prusoff equation from IC50-like values obtained from the percent displacement values at time point, at which system has reached equilibrium; kon = association rate constant; displacement traces at each compound concentration were fitted according to a monoexponential equation to yield kobs. Secondary plot of kobs over compound concentration was linearly fitted to generate kon; koff = dissociation rate constant (= Kd × kon); residence time = 1/koff. From standard errors of IC50 and kon calculated in regression analysis for curve fitting, errors for Kd, koff, and residence time were calculated by Gaussian error propagation.