Table 1 Calculated inhibition and kinetic constants for a hypothetical drug
From: Erratum: Drug–target residence time and its implications for lead optimization
Target | Ki (nM) | Ki* (nM) | koff (s−1) | Dissociative t½ (s) |
|---|---|---|---|---|
Primary | 10 | 0.099 | 9 × 10−3 | 76 |
Secondary 1 | 1 | 0.4 | 0.2 | 3.10 |
Secondary 2 | 10 | 3 | 0.4 | 1.60 |
Secondary 3 | 50 | 50 | 1.0 | 1.00 |
The inhibitor is considered to be competitive with the substrates for all targets, and for which substrate concentrations in vivo reflect their Michaelis constants. For the kinetic scheme shown in equation 3, Ki = k2/k1 and Ki* = k2k4/(k1(k3 + k4)), koff = k2k4/(k2 + k3 + k4); and t1/2 = 0.693/koff. For all four targets, k1 = 109 M−1s−1, whereas other rate constants for the four targets were, respectively: k2 (s−1) = 10, 1, 10, 50; k3 (s−1) = 1, 0.75, 1, 0; and k4 (s−1) = 0.01, 0.5, 0.5, 1.0. | ||||
