Quantification of Enzyme–Inhibitor Pharmacological Actions
- 1Institute of Fundamental Medicine and Biology, Kazan Federal University, 18 Kremlyovskaya St., 420008 Kazan, Russia
- 2Arbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center of RAS, Arbuzov Str. 8, 420088 Kazan, Russia
Abstract
Quantitative measurement of enzyme–drug interactions has become a key step in the process of drug discovery. More and more studies refer to the determination of the operational index, IC50, the half-maximal inhibitory concentration, from dose–response curves, instead of the determination of the exact dissociation constant, Ki, a true thermodynamic parameter that measures the affinity and provides information on binding mechanisms. Although knowledge of IC50 is useful for rapid screening and comparison of new molecules, it depends on experimental conditions, in particular substrate and enzyme concentration, type of inhibitor, and incubation time with inhibitor. Thus, IC50 values can be misleading in cases of allosteric inhibition, partial inhibition, slow-tight binding and progressive inhibition (covalent inhibition). As a consequence, the relationships between IC50 and Ki strongly depend on catalytic and inhibition mechanistic models and experimental conditions. The present review provides relationships between IC50 and Ki for simple and complex mechanisms of enzyme inhibition and highlights the interest of a thorough analysis of binding processes and irreversible reactions with inhibitors to describe the potentialities of new pharmacologically active compounds, acting either on Michaelian or non-Michaelian enzymes.
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BibTeX
@article{masson2026quantification,
title = {{Quantification of Enzyme–Inhibitor Pharmacological Actions}},
author = {Patrick Masson and Tatiana Pashirova},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = oct,
doi = {10.3390/ijms27219565},
url = {https://www.mdpi.com/1422-0067/27/21/9565},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Quantification of Enzyme–Inhibitor Pharmacological Actions
AU - Patrick Masson
AU - Tatiana Pashirova
PY - 2026
DA - 2026/10/26
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27219565
UR - https://www.mdpi.com/1422-0067/27/21/9565
AB - Quantitative measurement of enzyme–drug interactions has become a key step in the process of drug discovery. More and more studies refer to the determination of the operational index, IC50, the half-maximal inhibitory concentration, from dose–response curves, instead of the determination of the exact dissociation constant, Ki, a true thermodynamic parameter that measures the affinity and provides information on binding mechanisms. Although knowledge of IC50 is useful for rapid screening and comparison of new molecules, it depends on experimental conditions, in particular substrate and enzyme concentration, type of inhibitor, and incubation time with inhibitor. Thus, IC50 values can be misleading in cases of allosteric inhibition, partial inhibition, slow-tight binding and progressive inhibition (covalent inhibition). As a consequence, the relationships between IC50 and Ki strongly depend on catalytic and inhibition mechanistic models and experimental conditions. The present review provides relationships between IC50 and Ki for simple and complex mechanisms of enzyme inhibition and highlights the interest of a thorough analysis of binding processes and irreversible reactions with inhibitors to describe the potentialities of new pharmacologically active compounds, acting either on Michaelian or non-Michaelian enzymes.
SN - 1422-0067
ER -