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,, was measured from data shown in Figure4D.andwere determined from data shown in Figure4panels A and B, respectively. For the subsequent slow steps, the t1/2values are first-order complex half-times calculated using the rate constants given in blue for each step. Thevalue presented is the limiting (fastest) rate, which was determined by plotting the Mg2+-dependentvalues measured in Figure4Dagainst [Mg2+] and extrapolating to [Mg2+]=0 M.
