Abstract
A major strategy used in drug design is the inhibition of enzyme activity. The ability to accurately measure the concentration of the inhibitor which is required to inhibit a given biological or biochemical function by half is extremely important in ranking compounds. Since the concept of the half maximal inhibitory concentration (IC50) is used extensively for studying reversible inhibition enzymatic reactions, it is important to clearly understand the experimental design and the mathematical modeling techniques used to generate IC50 values. The most important part of the experimental design is to measure the rate of production of [P] during the linear phase of the time course of the reaction and to prove that the enzyme- catalyzed reaction is reversible. The most important part of the mathematical modeling is to select the correct model and to have a firm understanding on how to handle outliers in the data. These topics are discussed in greater detail along with a discussion on how much quantitative and mechanistic information can be reasonably deduced from an experiment.
Keywords: IC50, Ki, EC50, kinetic parameters, assay conditions, data fitting strategies, mathematical modeling techniques, antagonists, cyclooxygenase (COX) enzymes, invitro cell assays, insect cell assay
Current Topics in Medicinal Chemistry
Title:The IC50 Concept Revisited
Volume: 12 Issue: 11
Author(s): Gary W. Caldwell, Zhengyin Yan, Wensheng Lang and John A. Masucci
Affiliation:
Keywords: IC50, Ki, EC50, kinetic parameters, assay conditions, data fitting strategies, mathematical modeling techniques, antagonists, cyclooxygenase (COX) enzymes, invitro cell assays, insect cell assay
Abstract: A major strategy used in drug design is the inhibition of enzyme activity. The ability to accurately measure the concentration of the inhibitor which is required to inhibit a given biological or biochemical function by half is extremely important in ranking compounds. Since the concept of the half maximal inhibitory concentration (IC50) is used extensively for studying reversible inhibition enzymatic reactions, it is important to clearly understand the experimental design and the mathematical modeling techniques used to generate IC50 values. The most important part of the experimental design is to measure the rate of production of [P] during the linear phase of the time course of the reaction and to prove that the enzyme- catalyzed reaction is reversible. The most important part of the mathematical modeling is to select the correct model and to have a firm understanding on how to handle outliers in the data. These topics are discussed in greater detail along with a discussion on how much quantitative and mechanistic information can be reasonably deduced from an experiment.
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Cite this article as:
W. Caldwell Gary, Yan Zhengyin, Lang Wensheng and A. Masucci John, The IC50 Concept Revisited, Current Topics in Medicinal Chemistry 2012; 12 (11) . https://dx.doi.org/10.2174/156802612800672844
DOI https://dx.doi.org/10.2174/156802612800672844 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
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