%0 Journal Article
%T When Biochemical Potency Misrepresents Pharmacological Persistence: A Theoretical Analysis of Inhibitor Binding Kinetics, Target Resynthesis, and Pathway Recovery Following Transient Drug Exposure
%A Hannah Brooks
%A Oliver Hayes
%J Journal of Biochemical Technology
%@ 0974-2328
%D 2026
%V 17
%N 3
%R 10.51847/4iAhPswSN5
%P 92-101
%X Biochemical potency is often summarized by equilibrium measurements that describe how strongly an inhibitor suppresses or binds a target under a defined assay condition. Such measurements do not, by themselves, specify how long pharmacological effects persist once free drug concentrations decline. This theoretical analysis examines when that mismatch becomes consequential. Evidence from drug-target kinetic studies, target-engagement methods, covalent and reversible-covalent inhibition, target-turnover models, clinical Bruton tyrosine kinase pharmacodynamics, and post-washout experimental systems was integrated without generating new empirical data. The analysis separates four temporally distinct processes: disappearance of free inhibitor, loss or persistence of target occupancy, replacement of inhibited target by newly synthesized protein, and recovery of downstream pathway function. Published evidence supports a conditional rather than universal relationship between biochemical potency and persistence. Slow dissociation, irreversible or slowly reversible engagement, and sustained target occupancy can extend effects beyond plasma exposure, but their influence depends on target turnover, biological context, intracellular accessibility, and pathway architecture. Conversely, rapid target resynthesis or compensatory pathway activity can shorten functional persistence even when inhibitor-target engagement is durable. Target-level recovery and pathway-level recovery therefore need not occur on the same time scale. Pharmacological persistence is best interpreted as an emergent temporal property of interacting exposure, binding, target-renewal, and network-recovery processes rather than as a direct extension of equilibrium potency. Mechanistic claims about persistence should therefore specify which temporal process was measured and which remained inferred.
%U https://jbiochemtech.com/article/when-biochemical-potency-misrepresents-pharmacological-persistence-a-theoretical-analysis-of-inhibi-51tiado0bfkbhqw