Slow-binding inhibitors of enzymes: kinetic characteristics and pharmacological interest
Shaihutdinova Z.M.2, Pashirova T.N.1, Masson P.2
1. Kazan (Volga region) Federal University, Kazan, Russia; Arbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center, Russian Academy of Sciences, Kazan, Russia 2. Kazan (Volga region) Federal University, Kazan, Russia
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.
Download PDF:
Keywords: slow-binding inhibitors, enzyme kinetics, inhibition constant, residence time
Citation:
Shaihutdinova Z.M., Pashirova T.N., Masson P. (2025) Slow-binding inhibitors of enzymes: kinetic characteristics and pharmacological interest. Biomeditsinskaya Khimiya, 71(2), 81-94.
Shaihutdinova Z.M. et al. Slow-binding inhibitors of enzymes: kinetic characteristics and pharmacological interest // Biomeditsinskaya Khimiya. - 2025. - V. 71. -N 2. - P. 81-94.
Shaihutdinova Z.M. et al., "Slow-binding inhibitors of enzymes: kinetic characteristics and pharmacological interest." Biomeditsinskaya Khimiya 71.2 (2025): 81-94.
Shaihutdinova, Z. M., Pashirova, T. N., Masson, P. (2025). Slow-binding inhibitors of enzymes: kinetic characteristics and pharmacological interest. Biomeditsinskaya Khimiya, 71(2), 81-94.
References
Borisov D.V., Veselovsky A.V. (2020) Ligand-receptor binding kinetics in drug design. Biomeditsinskaya Khimiya, 66(1), 42–53. CrossRef Scholar google search
Masson P., Lushchekina S.V. (2016) Slow-binding inhibition of cholinesterases, pharmacological and toxicological relevance. Arch. Biochem. Biophys., 593, 60–68. CrossRef Scholar google search
Copeland R.A., Pompliano D.L., Meek T.D. (2006) Drug-target residence time and its implications for lead optimization. Nat. Rev. Drug Discov., 5(9), 730–739. CrossRef Scholar google search
Knockenhauer K.E., Copeland R.A. (2024) The importance of binding kinetics and drug-target residence time in pharmacology. Br. J. Pharmacol., 181(21), 4103–4116. CrossRef Scholar google search
Sharma S., Joshi S., Kalidindi T., Digwal C.S., Panchal P., Lee S.-G., Zanzonico P., Pillarsetty N., Chiosis G. (2023) Unraveling the mechanism of epichaperome modulation by zelavespib: biochemical insights on target occupancy and extended residence time at the site of action. Biomedicines, 11(10), 2599. CrossRef Scholar google search
Swinney D.C. (2004) Biochemical mechanisms of drug action: what does it take for success? Nat. Rev. Drug Discov., 3(9), 801–808. CrossRef Scholar google search
Vauquelin G., Charlton S.J. (2010) Long-lasting target binding and rebinding as mechanisms to prolong in vivo drug action. Br. J. Pharmacol., 161(3), 488–508. CrossRef Scholar google search
Lu H., Tonge P.J. (2010) Drug-target residence time: critical information for lead optimization. Curr. Opin. Chem. Biol., 14(4), 467-474. CrossRef Scholar google search
Yang H., Li X., Li G., Huang H., Yang W., Jiang X., Sen M., Liu J., Liu Y., Pan Y., Wang G. (2021) Accurate quantitative determination of affinity and binding kinetics for tight binding inhibition of xanthine oxidase. Biomed. Pharmacother., 139, 111664. CrossRef Scholar google search
Dahl G., Akerud T. (2013) Pharmacokinetics and the drug-target residence time concept. Drug Discov. Today, 18(15–16), 697–707. CrossRef Scholar google search
Lee K.S.S., Yang J., Niu J., Ng C.J., Wagner K.M., Dong H., Kodani S.D., Wan D., Morisseau C., Hammock B.D. (2019) Drug-target residence time affects in vivo target occupancy through multiple pathways. ACS Central Science, 5(9), 1614–1624. CrossRef Scholar google search
Hoare S.R.J. (2021) The problems of applying classical pharmacology analysis to modern in vitro drug discovery assays: slow binding kinetics and high target concentration. SLAS Discovery, 26(7), 835–850. CrossRef Scholar google search
Zhang R., Wong K. (2017) High performance enzyme kinetics of turnover, activation and inhibition for translational drug discovery. Expert Opin. Drug Discov., 12(1), 17–37. CrossRef Scholar google search
Srinivasan B., Flórez Weidinger J.D., Zhai X., Lemercier G., Ikeda T., Brewer M., Zhang B., Heyse S., Wingfield J., Steigele S. (2022) High-throughput mechanistic screening of non-equilibrium inhibitors by a fully automated data analysis pipeline in early drug-discovery. SLAS Discovery, 27(8), 460–470. CrossRef Scholar google search
Lushchekina S.V., Masson P. (2020) Slow-binding inhibitors of acetylcholinesterase of medical interest. Neuropharmacology, 177, 108236. CrossRef Scholar google search
Mukherjee A., Zamani F., Suzuki T. (2023) Evolution of slow-binding inhibitors targeting histone deacetylase isoforms. J. Med. Chem., 66(17), 11672–11700. CrossRef Scholar google search
Bondarev A.D., Attwood M.M., Jonsson J., Chubarev V.N., Tarasov V.V., Schiöth H.B. (2021) Recent developments of HDAC inhibitors: emerging indications and novel molecules. Br. J. Clin. Pharmacol., 87(12), 4577–4597. CrossRef Scholar google search
Fridovich I. (1968) A study of the interaction of acetoacetic decarboxylase with several inhibitors. J. Biol. Chem., 243(5), 1043–1051. CrossRef Scholar google search
Wentworth D.F., Wolfenden R. (1974) Slow binding of D-galactal, a reversible inhibitor of bacterial β-galactosidase. Biochemistry, 13(23), 4715–4720. CrossRef Scholar google search
Wentworth D.F., Wolfenden R. (1975) Interaction of 3,4,5,6-tetrahydrouridine with human liver cytidine deaminase. Biochemistry, 14(23), 5099–5105. CrossRef Scholar google search
Morrison J.F. (1982) The slow-binding and slow, tight-binding inhibition of enzyme-catalysed reactions. Trends Biochem. Sci., 7(3), 102–105. CrossRef Scholar google search
Almeida L., Rocha J.F., Falcão A., Nuno Palma P., Loureiro A.I., Pinto R., Bonifácio M.J., Wright L.C., Nunes T., Soares-da-Silva P. (2013) Pharmacokinetics, pharmacodynamics and tolerability of opicapone, a novel catechol-o-methyltransferase inhibitor, in healthy subjects. Clin. Pharmacokinet., 52(2), 139–151. CrossRef Scholar google search
Ren T., Zhu X., Jusko N.M., Krzyzanski W., Jusko W.J. (2022) Pharmacodynamic model of slow reversible binding and its applications in pharmacokinetic/pharmacodynamic modeling: review and tutorial. J. Pharmacokinet. Pharmacodyn., 49(5), 493–510. CrossRef Scholar google search
Kwon Y.-J., Lee J., Seo E.-B., Lee J., Park J., Kim S.-K., Yu H., Ye S.-K., Chang P.-S. (2024) Cysteine protease I29 propeptide from Calotropis procera R. Br. as a potent cathepsin L inhibitor and its suppressive activity in breast cancer metastasis. Sci. Rep., 14(1), 23218. CrossRef Scholar google search
Shah A.B., Baiseitova A., Lee G., Kim J.H., Park K.H. (2024) Analogues of dihydroflavonol and flavone as protein tyrosine phosphatase 1B inhibitors from the leaves of Artocarpus elasticus. ACS Omega, 9(8), 9053–9062. CrossRef Scholar google search
Chen Z., Du R., Cooper L., Achi J.G., Dong M., Ran Y., Zhang J., Zhan P., Rong L., Cui Q. (2023) Sulforaphane is a reversible inhibitor of 3-chymotrypsin-like protease of SARS-CoV-2. J. Med. Virol., 95(3), e28609. CrossRef Scholar google search
de Witte W.E.A., Danhof M., van der Graaf P.H., de Lange E.C.M. (2016) In vivo target residence time and kinetic selectivity: the association rate constant as determinant. Trends Pharmacol. Sci., 37(10), 831–842. CrossRef Scholar google search
Walkup G.K., You Z., Ross P.L., Allen E.K.H., Daryaee F., Hale M.R., O'Donnell J., Ehmann D.E., Schuck V.J.A., Buurman E.T., Choy A.L., Hajec L., Murphy-Benenato K., Marone V., Patey S.A., Grosser L.A., Johnstone M., Walker S.G., Tonge P.J., Fisher S.L. (2015) Translating slow-binding inhibition kinetics into cellular and in vivo effects. Nat. Chem. Biol., 11(6), 416–423. CrossRef Scholar google search
Spassov D.S. (2024) Binding affinity determination in drug design: insights from lock and key, induced fit, conformational selection, and inhibitor trapping models. Int. J. Mol. Sci., 25(13), 7124. CrossRef Scholar google search
Srinivasan B. (2023) A guide to enzyme kinetics in early drug discovery. FEBS J., 290(9), 2292–2305. CrossRef Scholar google search
Lamba D., Pesaresi A. (2022) Kinetic modeling of timedependent enzyme inhibition by pre-steady-state analysis of progress curves: the case study of the anti-Alzheimer's drug galantamine. Int. J. Mol. Sci., 23(9), 5072. CrossRef Scholar google search
Copeland R.A. (2021) Evolution of the drug-target residence time model. Expert Opin. Drug Discov., 16(12), 1441–1451. CrossRef Scholar google search
Liu H., Zhang H., IJzerman A.P., Guo D. (2024) The translational value of ligand-receptor binding kinetics in drug discovery. Br. J. Pharmacol., 181(21), 4117–4129. CrossRef Scholar google search
Vauquelin G. (2016) Effects of target binding kinetics on in vivo drug efficacy: koff, kon and rebinding. Br. J. Pharmacol., 173(15), 2319–2334. CrossRef Scholar google search
Ziada S., Diharce J., Raimbaud E., Aci-Sèche S., Ducrot P., Bonnet P. (2022) Estimation of drug-target residence time by targeted molecular dynamics simulations. J. Chem. Inf. Model., 62(22), 5536–5549. CrossRef Scholar google search
Araki M., Matsumoto S., Bekker G.-J., Isaka Y., Sagae Y., Kamiya N., Okuno Y. (2021) Exploring ligand binding pathways on proteins using hypersound-accelerated molecular dynamics. Nat. Commun., 12(1), 2793. CrossRef Scholar google search
Wang J., Do H.N., Koirala K., Miao Y. (2023) Predicting biomolecular binding kinetics: a review. J. Chem. Theory Comput., 19(8), 2135–2148. CrossRef Scholar google search
Morrison J.F., Walsh C.T. (1988) The behavior and significance of slow-binding enzyme inhibitors. Adv. Enzymol. Relat. Areas Mol. Biol., 61, 201–301. CrossRef Scholar google search
Goličnik M., Stojan J. (2004) Slow-binding inhibition: a theoretical and practical course for students. Biochem. Mol. Biol. Educ., 32(4), 228–235. CrossRef Scholar google search
Masson P. (2012) Time-dependent kinetic complexities in cholinesterase-catalyzed reactions. Biochemistry (Moscow), 77(10), 1147–1161. CrossRef Scholar google search
Pellock S.J., Creekmore B.C., Walton W.G., Mehta N., Biernat K.A., Cesmat A.P., Ariyarathna Y., Dunn Z.D., Li B., Jin J., James L.I., Redinbo M.R. (2018) Gut microbial β-glucuronidase inhibition via catalytic cycle interception. ACS Central Science, 4(7), 868–879. CrossRef Scholar google search
Cornish Bowden A. (1974) A simple graphical method for determining the inhibition constants of mixed, uncompetitive and non competitive inhibitors. Biochem. J., 137(1), 143–144. CrossRef Scholar google search
Tian W.X., Tsou C.L. (1982) Determination of the rate constant of enzyme modification by measuring the substrate reaction in the presence of the modifier. Biochemistry, 21(5), 1028–1032. CrossRef Scholar google search
Cha S. (1975) Tight-binding inhibitors-I: kinetic behavior. Biochem. Pharmacol., 24(23), 2177–2185. CrossRef Scholar google search
Copeland R.A. (2011) Conformational adaptation in drug-target interactions and residence time. Future Med. Chem., 3(12), 1491–1501. CrossRef Scholar google search
Fagnani L., Nazzicone L., Bellio P., Franceschini N., Tondi D., Verri A., Petricca S., Iorio R., Amicosante G., Perilli M., Celenza G. (2022) Protocetraric and salazinic acids as potential inhibitors of SARS-CoV-2 3CL protease: biochemical, cytotoxic, and computational characterization of depsidones as slow-binding inactivators. Pharmaceuticals, 15(6), 714. CrossRef Scholar google search
Cellupica E., Caprini G., Cordella P., Cukier C., Fossati G., Marchini M., Rocchio I., Sandrone G., Vanoni M.A., Vergani B., Źrubek K., Stevenazzi A., Steinkühler C. (2023) Difluoromethyl-1,3,4-oxadiazoles are slow-binding substrate analog inhibitors of histone deacetylase 6 with unprecedented isotype selectivity. J. Biol. Chem., 299(1), 102800. CrossRef Scholar google search
Mucha A., Drag M., Dalton J.P., Kafarski P. (2010) Metallo-aminopeptidase inhibitors. Biochimie, 92(11), 1509–1529. CrossRef Scholar google search
Rich D.H., Moon B.J., Harbeson S. (1984) Inhibition of aminopeptidases by amastatin and bestatin derivatives. Effect of inhibitor structure on slow-binding processes. J. Med. Chem., 27(4), 417–422. CrossRef Scholar google search
Wilkes S.H., Prescott J.M. (1985) The slow, tight binding of bestatin and amastatin to aminopeptidases. J. Biol. Chem., 260(24), 13154–13162. CrossRef Scholar google search
Zueva I.V., Lushchekina S.V., Pottie I.R., Darvesh S., Masson P. (2020) 1-(3-Tert-butylphenyl)-2,2,2-trifluoroethanone as a potent transition-state analogue slow-binding inhibitor of human acetylcholinesterase: kinetic, MD and QM/MM studies. Biomolecules, 10(12), 1–21. CrossRef Scholar google search
Carletti E., Schopfer L.M., Colletier J.-P., Froment M.-T., Nachon F., Weik M., Lockridge O., Masson P. (2011) Reaction of cresyl saligenin phosphate, the organophosphorus agent implicated in aerotoxic syndrome, with human cholinesterases: mechanistic studies employing kinetics, mass spectrometry, and X-ray structure analysis. Chem. Res. Toxicol., 24(6), 797–808. CrossRef Scholar google search
Zueva I., Lushchekina S., Shulnikova P., Lenina O., Petrov K., Molochkina E., Masson P. (2021) α-Tocopherol, a slow-binding inhibitor of acetylcholinesterase. Chem. Biol. Interact., 348, 109646. CrossRef Scholar google search
Mukhametgalieva A.R., Nemtarev A.V., Sykaev V.V., Pashirova T.N., Masson P. (2023) Activation/inhibition of cholinesterases by excess substrate: interpretation of the phenomenological b factor in steady-state rate equation. Int. J. Mol. Sci., 24(13), 10472. CrossRef Scholar google search
Masson P., Mukhametgalieva A.R. (2023) Partial reversible inhibition of enzymes and its metabolic and pharmacotoxicological implications. Int. J. Mol. Sci., 24(16), 12973. CrossRef Scholar google search
Wenthur C.J., Gentry P.R., Mathews T.P., Lindsley C.W. (2014) Drugs for allosteric sites on receptors. Annu. Rev. Pharmacol. Toxicol., 54(1), 165–184. CrossRef Scholar google search
Segel I.H. (1993) In: Enzyme Kinetics: Behavior and Analysis of Rapid Equilibrium and Steady-State Enzyme Systems. Wiley, 992 p. Scholar google search
Kurganov B.I., Dorozhko A.I., Kagan Z.S., Yakovlev V.A. (1976) The theoretical analysis of kinetic behaviour of “hysteretic” allosteric enzymes. I. The kinetic manifestations of slow conformational change of an oligomeric enzyme in the Monod, Wyman and Changeux model. J. Theor. Biol., 60(2), 247–269. CrossRef Scholar google search
Auzat I., Gawlita E., Garel J.-R. (1995) Slow ligand-induced transitions in the allosteric phosphofructokinase from Escherichia coli. J. Mol. Biol., 249(2), 478–492. CrossRef Scholar google search
Pargellis C., Tong L., Churchill L., Cirillo P.F., Gilmore T., Graham A.G., Grob P.M., Hickey E.R., Moss N., Pav S., Regan J. (2002) Inhibition of p38 MAP kinase by utilizing a novel allosteric binding site. Nat. Struct. Mol. Biol., 9(4), 268–272. CrossRef Scholar google search
Casey A.K., Baugh J., Frantom P.A. (2012) The slow-onset nature of allosteric inhibition in α-isopropylmalate synthase from Mycobacterium tuberculosis is mediated by a flexible loop. Biochemistry, 51(24), 4773–4775. CrossRef Scholar google search
Goličnik M., Stojan J. (2002) Multi-step analysis as a tool for kinetic parameter estimation and mechanism discrimination in the reaction between tight-binding fasciculin 2 and electric eel acetylcholinesterase. Biochim. Biophys. Acta, 1597(1), 164–172. CrossRef Scholar google search
Radić Z., Duran R., Vellom D.C., Li Y., Cervenansky C., Taylor P. (1994) Site of fasciculin interaction with acetylcholinesterase. J. Biol. Chem., 269(15), 11233–11239. CrossRef Scholar google search
Chelliah J., Smith J.D., Fariss M.W. (1994) Inhibition of cholinesterase activity by tetrahydroaminoacridine and the hemisuccinate esters of tocopherol and cholesterol. Biochim. Biophys. Acta, 1206(1), 17–26. CrossRef Scholar google search
Sepčić K., Marcel V., Klaebe A., Turk T., Šuput D., Fournier D. (1998) Inhibition of acetylcholinesterase by an alkylpyridinium polymer from the marine sponge, Reniera sarai. Biochim. Biophys. Acta, 1387(1–2), 217–225. CrossRef Scholar google search
Ashani Y., Peggins J.O., Doctor B.P. (1992) Mechanism of inhibition of cholinesterases by huperzine A. Biochem. Biophys. Res. Commun., 184(2), 719–726. CrossRef Scholar google search
Stojan J., Pavli M.R. (1997) Mechanism of eserine action on the hydrolysis of butyrylthiocholine by butyrylcholinesterase. J. Enzyme Inhib., 11(3), 199–208. CrossRef Scholar google search
Kim J.H., Lee S., Park S., Park J.S., Kim Y.H., Yang S.Y. (2019) Slow-binding inhibition of tyrosinase by Ecklonia cava phlorotannins. Marine Drugs, 17(6), 359. CrossRef Scholar google search
Kim J.H., Jang D.H., Lee K.W., Kim K.D., Shah A.B., Zhumanova K., Park K.H. (2020) Tyrosinase inhibition and kinetic details of puerol A having but-2-enolide structure from Amorpha fruticosa. Molecules, 25(10), 2344. CrossRef Scholar google search
Wang Y., Kim J.Y., Song Y.H., Li Z.P., Yoon S.H., Uddin Z., Ban Y.J., Lee K.W., Park K.H. (2019) Highly potent bacterial neuraminidase inhibitors, chromenone derivatives from Flemingia philippinensis. Int. J. Biol. Macromol., 128, 149–157. CrossRef Scholar google search
Kim J.Y., Li Z.P., Lee G., Kim J.H., Shah A.B., Lee Y.H., Park K.H. (2023) Investigation of bacterial neuraminidase inhibition of xanthones bearing geranyl and prenyl groups from Cratoxylum cochinchinense. Front. Chem., 11, 1245071. CrossRef Scholar google search
Woo H.S., Im H.J., Kim J.Y., Lee M.-S., Kim D.W. (2022) Mechanism of protein tyrosine phosphatase 1B inhibition by theaflavanoside IV isolated from methanolic extract of tea (Camellia sinensis) seed shells. Nat. Prod. Res., 36(12), 3189–3192. CrossRef Scholar google search
Shah A.B., Yoon S., Kim J.H., Zhumanova K., Ban Y.J., Lee K.W., Park K.H. (2020) Effectiveness of cyclohexyl functionality in ugonins from Helminthostachys zeylanica to PTP1B and α-glucosidase inhibitions. Int. J. Biol. Macromol., 165, 1822–1831. CrossRef Scholar google search
Kharlamova A.D., Lushchekina S.V., Petrov K.A., Kots E.D., Nachon F., Villard-Wandhammer M., Zueva I.V., Krejci E., Reznik V.S., Zobov V.V., Nikolsky E.E., Masson P. (2016) Slow-binding inhibition of acetylcholinesterase by an alkylammonium derivative of 6-methyluracil: mechanism and possible advantages for myasthenia gravis treatment. Biochem. J., 473(9), 1225–1236. CrossRef Scholar google search
Lenina O.A., Zueva I.V., Zobov V.V., Semenov V.E., Masson P., Petrov K.A. (2020) Slow-binding reversible inhibitor of acetylcholinesterase with long-lasting action for prophylaxis of organophosphate poisoning. Sci. Rep., 10(1), 16611. CrossRef Scholar google search
Zhou Y., Fu Y., Yin W., Li J., Wang W., Bai F., Xu S., Gong Q., Peng T., Hong Y., Zhang D., Zhang D., Liu Q., Xu Y., Xu H.E., Zhang H., Jiang H., Liu H. (2021) Kinetics-driven drug design strategy for next-generation acetylcholinesterase inhibitors to clinical candidate. J. Med. Chem., 64(4), 1844–1855. CrossRef Scholar google search
Qian H., Yu C., Zhu H., Ding Q., Cai Y., Jing J., Xu X., Guo R., Zhang H., Liu H., Chen X., Liu Y. (2023) Safety, tolerability, and pharmacokinetics of fluoropezil (DC20), a novel acetylcholinesterase inhibitor: a phase I study in healthy young and elderly Chinese subjects. Clin. Transl. Sci., 16(5), 810–822. CrossRef Scholar google search
Montgomery J.I., Brown M.F., Reilly U., Price L.M., Abramite J.A., Arcari J., Barham R., Che Y., Chen J.M., Chung S.W., Collantes E.M., Desbonnet C., Doroski M., Doty J., Engtrakul J.J., Harris T.M., Huband M., Knafels J.D., Leach K.L., Liu S., Marfat A., McAllister L., McElroy E., Menard C.A., Mitton-Fry M., Mullins L., Noe M.C., O'Donnell J., Oliver R., Penzien J., Plummer M., Shanmugasundaram V., Thoma C., Tomaras A.P., Uccello D.P., Vaz A., Wishka D.G. (2012) Pyridone methylsulfone hydroxamate LpxC inhibitors for the treatment of serious gram-negative infections. J. Med. Chem., 55(4), 1662–1670. CrossRef Scholar google search
Basak S., Li Y., Tao S., Daryaee F., Merino J., Gu C., Delker S.L., Phan J.N., Edwards T.E., Walker S.G., Tonge P.J. (2022) Structure-kinetic relationship studies for the development of long residence time LpxC inhibitors. J. Med. Chem., 65(17), 11854–11875. CrossRef Scholar google search
Cellupica E., Caprini G., Fossati G., Mirdita D., Cordella P., Marchini M., Rocchio I., Sandrone G., Stevenazzi A., Vergani B., Steinkühler C., Vanoni M.A. (2023) The importance of the “time factor” for the evaluation of inhibition mechanisms: the case of selected HDAC6 inhibitors. Biology (Basel), 12(8), 1049. CrossRef Scholar google search
Hasinoff B.B., Patel D. (2018) Myocyte-damaging effects and binding kinetics of boronic acid and epoxyketone proteasomal-targeted drugs. Cardiovasc. Toxicol., 18(6), 557–568. CrossRef Scholar google search
Wiedemeyer S.J.A., Wu G., Pham T.L.P., Lang-Henkel H., Perez Urzua B., Whisstock J.C., Law R.H.P., Steinmetzer T. (2023) Synthesis and structural characterization of macrocyclic plasmin inhibitors. ChemMedChem, 18(6), e202200632. CrossRef Scholar google search
Ntatsopoulos V., Macegoniuk K., Mucha A., Vassiliou S., Berlicki Ł. (2018) Structural exploration of cinnamate-based phosphonic acids as inhibitors of bacterial ureases. Eur. J. Med. Chem., 159, 307–316. CrossRef Scholar google search
Pagoni A., Grabowiecka A., Tabor W., Mucha A., Vassiliou S., Berlicki Ł. (2021) Covalent inhibition of bacterial urease by bifunctional catechol-based phosphonates and phosphinates. J. Med. Chem., 64(1), 404–416. CrossRef Scholar google search
Vauquelin G., Maes D. (2023) Competition in drug binding and the race to equilibrium. Fundam. Clin. Pharmacol., 37(1), 147–157. CrossRef Scholar google search
