Slow-binding inhibitors of enzymes: kinetic characteristics and pharmacological interest

Currently, the search for new slow-binding inhibitors of enzymes (SBI) and their identification primary in vitro studies still attracts much attention in the context of their potential role as putative pharmacological agents for the treatment of various diseases. In contrast to their classical reversible analogues, SBI exhibit a slow enzyme binding kinetics, where the equilibrium steady-state is reached not in microseconds, but after longer time intervals. Such compounds could be promising drugs, because regardless of their pharmacokinetics in the bloodstream, they have such advantages as high affinity for the target enzyme, long residence time on the target, and therefore, prolonged action. These pharmacological properties ensure optimized dosage of drugs required to achieve high activity with less side effects. In this review we have considered mechanisms of SBI interaction with enzyme targets, the principles of their recognition at the level of in vitro studies and analysis of binding and kinetic parameters.