Figure 6.

Timeline for the inhibition of IDH1 R132H by Ivosidenib showing the fast and slow steps involved. For simplicity, the binding/dissociation steps for 2OG and Mg²⁺ are shown at a single monomer active site, (though there is likely half‐site reactivity). The pre‐equilibrium dissociation constant, $K_{\mathrm{d}}^{\mathrm{pre}}$ , was measured from data shown in Figure 4D. $K_{\mathrm{d}}^{2\mathrm{OG}}$ and $K_{\mathrm{d}}^{{\mathrm{Mg}}^{2+}}$ were determined from data shown in Figure 4 panels A and B, respectively. For the subsequent slow steps, the t_1/2 values are first‐order complex half‐times calculated using the rate constants given in blue for each step. The $k_{\mathrm{on}}^{\mathrm{trans}}$ value presented is the limiting (fastest) rate, which was determined by plotting the Mg²⁺‐dependent $k_{\mathrm{on}}^{\mathrm{trans}}$ values measured in Figure 4D against [Mg²⁺] and extrapolating to [Mg²⁺]=0 M.