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Tytuł:
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[Ligand-receptor binding kinetics in drug design].
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Autorzy:
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Borisov DV; Institute of Biomedical Chemistry, Moscow, Russia.
Veselovsky AV; Institute of Biomedical Chemistry, Moscow, Russia.
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Transliterated Title:
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Kinetika sviazyvaniia liganda s retseptorom v razrabotke lekarstv.
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Źródło:
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Biomeditsinskaia khimiia [Biomed Khim] 2020 Jan; Vol. 66 (1), pp. 42-53.
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Typ publikacji:
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Journal Article; Review
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Język:
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Russian
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Imprint Name(s):
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Original Publication: Moskva : Rossiĭskai︠a︡ akademii︠a︡ medit︠s︡inskikh nauk, 2003-
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MeSH Terms:
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Drug Design*
Ligands*
Protein Binding*
Pharmaceutical Preparations/*chemistry
Kinetics ; Thermodynamics
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Contributed Indexing:
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Keywords: binding constant; kinetics; protein-ligand complex; rate constant; residence time; thermodynamics
Local Abstract: [Publisher, Russian] Traditsionno termodinamicheskie velichiny affinnosti rassmatrivaiut kak osnovnye kriterii pri razrabotke novykh lekarstvennykh preparatov. V bol'shinstve sluchaev éti velichiny izmeriaiutsia v sistemakh in vitro pri postoiannykh kontsentratsiiakh retseptora i liganda, chto sil'no otlichaetsia ot usloviĭ, v kotorykh deĭstvuet lekarstvo in vivo. Issledovaniia poslednikh let pokazali, chto pri otsenke éffektivnosti lekarstvennogo sredstva kinetika protsessa sviazyvaniia lekarstvennogo sredstva s retseptorom mozhet byt' stol' zhe vazhnoĭ, kak affinnost'. Éto privelo k rastushchemu interesu k opredeleniiu konstant skorosti assotsiatsii i dissotsiatsii kompleksov retseptor-ligand na étape doklinicheskikh issledovaniĭ kandidatov v lekarstva. Lekarstvennoe sredstvo s bolee dlitel'nym vremenem uderzhaniia mozhet kineticheski “vybirat'” odin retseptor po sravneniiu s drugim, deĭstvovat' pri nizkoĭ kontsentratsii v organizme. V rabote rassmotreny teoreticheskie osnovy sviazyvaniia belok-ligand, molekuliarnye determinanty, kontroliruiushchie kinetiku sviazyvaniia lekarstvennoe sredstvo-retseptor. Ponimanie molekuliarnykh osobennosteĭ, lezhashchikh v osnove kinetiki sviazyvaniia retseptor-belok, budet sposobstvovat' ratsional'nomu konstruirovaniiu lekarstv s zadannymi svoĭstvami.
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Substance Nomenclature:
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0 (Ligands)
0 (Pharmaceutical Preparations)
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Entry Date(s):
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Date Created: 20200303 Date Completed: 20200325 Latest Revision: 20221222
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Update Code:
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20240105
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DOI:
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10.18097/PBMC20206601042
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PMID:
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32116225
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Traditionally, the thermodynamic values of affinity are considered as the main criterion for the development of new drugs. Usually, these values for drugs are measured in vitro at steady concentrations of the receptor and ligand, which are differed from in vivo environment. Recent studies have shown that the kinetics of the process of drug binding to its receptor make significant contribution in the drug effectiveness. This has increased attention in characterizing and predicting the rate constants of association and dissociation of the receptor ligand at the stage of preclinical studies of drug candidates. A drug with a long residence time can determine ligand-receptor selectivity (kinetic selectivity), maintain pharmacological activity of the drug at its low concentration in vivo. The paper discusses the theoretical basis of protein-ligand binding, molecular determinants that control the kinetics of the drug-receptor binding. Understanding the molecular features underlying the kinetics of receptor-ligand binding will contribute to the rational design of drugs with desired properties.