IC50-to-Ki: a web-based tool for converting IC50 to Ki values for inhibitors of enzyme activity and ligand binding
TLDR
A new web-server tool estimates Ki values from experimentally determined IC50 values for inhibitors of enzymes and of binding reactions between macromolecules and ligands to enable end users to help gauge the quality of the underlying assumptions used in these calculations.Abstract:
A new web-server tool estimates Ki values from experimentally determined IC50 values for inhibitors of enzymes and of binding reactions between macromolecules (e.g. proteins, polynucleic acids) and ligands. This converter was developed to enable end users to help gauge the quality of the underlying assumptions used in these calculations which depend on the type of mechanism of inhibitor action and the concentrations of the interacting molecular species. Additional calculations are performed for nonclassical, tightly bound inhibitors of enzyme-substrate or of macromolecule-ligand systems in which free, rather than total concentrations of the reacting species are required. Required userdefined input values include the total enzyme (or another target molecule) and substrate (or ligand) concentrations, the Km of the enzyme-substrate (or the Kd of the target-ligand) reaction, and the IC50 value. Assumptions and caveats for these calculations are discussed along with examples taken from the literature. The host database for this converter contains kinetic constants and other data for inhibitors of the proteolytic clostridial neurotoxins (http:// botdb.abcc.ncifcrf.gov/toxin/kiConverter.jsp).read more
Citations
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Journal ArticleDOI
Membrane Assays to Characterize Interaction of Drugs with ABCB1.
Zsolt Fekete,Zsuzsanna Rajnai,Tünde Nagy,Katalin Tauberné Jakab,Anita Kurunczi,Katalin Gémes,Krisztina Herédi-Szabó,Ferenc Fülöp,Gábor Tóth,Maciej Czerwinski,Greg Loewen,Peter Krajcsi +11 more
TL;DR: The utility of membrane assays as tools to detect and rank order drug–transporter interactions can be used earlier in the drug development process by showing that interactions of compounds with ABCB1 can be measured with similar levels of potency in either assay.
Journal ArticleDOI
Structural basis of nirmatrelvir and ensitrelvir activity against naturally occurring polymorphisms of the SARS-CoV-2 main protease
G.D. Noske,Ellen de Souza Silva,Mariana Ortiz de Godoy,Isabela Dolci,R.S. Fernandes,Rafael Victorio Carvalho Guido,Peter Sjö,Glaucius Oliva,Andre S. Godoy +8 more
TL;DR: In this paper , enzymatically characterized 14 naturally occurring Mpro polymorphisms that are close to the binding site of these antivirals, and found that Nirmatrelvir retained its potency against most polymorphisms tested while mutants G143S and Q189K were associated with diminished inhibition constants.
Journal ArticleDOI
C-Glucopyranosyl-1,2,4-triazol-5-ones: synthesis and inhibition of glycogen phosphorylase.
TL;DR: The new glucose derivatives had weak or no inhibition of rabbit muscle glycogen phosphorylase b: the best inhibitor was 3-β-D-glucopyranosyl-1-(2-naphthyl)-1,2,4-triazol-5-one (Ki’s= 80 µM).
Journal ArticleDOI
N- versus C-Domain Selectivity of Catalytic Inactivation of Human Angiotensin Converting Enzyme by Lisinopril-Coupled Transition Metal Chelates
TL;DR: The results of this study demonstrate the ability to optimize the target selectivity of catalytic metallopeptides through both binding and catalytic factors (double-filter effect).
Journal ArticleDOI
Discovery of Benzyl Tetraphosphonate Derivative as Inhibitor of Human Factor Xia.
TL;DR: Overall, inhibitor 1 is the first benzyl tetraphosphonate small molecule that allosterically inhibits human FXIa, blocks its physiological function, and prevents its zymogen activation by other clotting factors under in vitro conditions.
References
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Journal ArticleDOI
Relationship between the inhibition constant (K1) and the concentration of inhibitor which causes 50 per cent inhibition (I50) of an enzymatic reaction.
TL;DR: The analysis described shows K I does not equal I 50 when competitive inhibition kinetics apply; however, K I is equal to I 50 under conditions of either noncompetitive or uncompetitive kinetics.
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Development and optimization of a binding assay for the XIAP BIR3 domain using fluorescence polarization
Zaneta Nikolovska-Coleska,Renxiao Wang,Xueliang Fang,Hongguang Pan,York Tomita,Peng Li,Peter P. Roller,Krzysztof Krajewski,Naoyuki G. Saito,Jeanne A. Stuckey,Shaomeng Wang +10 more
TL;DR: The development of a homogeneous high-throughput assay based on fluorescence polarization for measuring the binding affinities of small-molecule inhibitors to the BIR3 domain of XIAP and results obtained indicated that the FP-based competitive binding assay performs correctly as designed.
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A linear equation that describes the steady-state kinetics of enzymes and subcellular particles interacting with tightly bound inhibitors.
TL;DR: D dose-response measurements generate a linear plot of inhibitor concentration divided by degree of inhibition against velocity without inhibitor divided by velocity with inhibitor, which indicates that the inhibitors of oxidative phosphorylation, rutamycin and bongkrekic acid, are tightly bound to rat liver mitochondria.
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BRENDA, AMENDA and FRENDA the enzyme information system: new content and tools in 2009
TL;DR: The web service via a SOAP (Simple Object Access Protocol) interface for access to the BRENDA data has been further enhanced and a new search option provides the access to protein-specific data.
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Fluorescence Polarization Competition Assay: The Range of Resolvable Inhibitor Potency Is Limited by the Affinity of the Fluorescent Ligand
TL;DR: The higher the affinity of the fluorescent ligand, the wider the range of inhibitor potency that can be resolved, and an approximate estimate for the low end of inhibitor K(i) values thatCan be resolved is the K(d) value of theorescent ligand.