Table 1.

Binding constants and parameters for Drugs A and B. The difference in Gibbs‐free energy between the ground state R and the final R′L state of both drugs is equal, and the corresponding thermodynamic K _D (i.e. (k₂.k₄)/(k₁.k₃)) is set to 4 × 10⁻⁹ M, as in 2016. k₁ = 1.10⁶ M⁻¹·min⁻¹ and k₂ = 4 min⁻¹ for both; k₂ = 64 min⁻¹ for Drug A and 0.24 min⁻¹ for Drug B; k₄ = (K _D.k₁.k₃)/k₂. The first step is only governed by k₁ and k₂. The ‘macroscopic’ dissociation rate constant, k_off, can be calculated by using Equation 4 or 6 in Figure 1B. The ‘macroscopic’ affinity constant, K _D*, represents the concentration of free ligand, [L], at which the occupancy of the target is half maximal at equilibrium and is calculated by using Equation 5 in Figure 1B. As k₄ << k₃, K _D* can be set equal to K _D

	First step	Drug A	Drug B
K D* (nM)	4000	4	4
koff (min−1)	4	3.76·10−3	2.35·10−4
k1.K D* (min−1)	4	4.00·10−3	4.00·10−3
k4 (min−1)	‐	6.40·10−2	2.50·10−4