The EC50 is defined quite simply as the concentration of agonist that provokes a response halfway between the baseline Bottom and maximum response Top. It is impossible to define the EC50 until you first define the baseline and maximum response. For instance, in the example below, the data are normalized to percentage of maximum response, without subtracting a baseline. The concentration that provokes a response of 50 in this experiment is not the EC Don't over interpret the EC It is simply the concentration of agonist required to provoke a response halfway between the baseline and maximum responses.
However, the EC50 is usually not the same as the Kd for the binding of agonist to its receptor -- it is not a direct measure of drug affinity. The pEC50 is defined as the negative logarithm of the EC There is no particular advantage to expressing potency this way, but it is customary in some fields.
In many experiments, you vary the concentration of an inhibitor. With more inhibitor, the response decreases, so the dose-response curve goes downhill. With such experiments, the midpoint is often called the IC50 "I" for inhibition rather than the EC50 "E" for effective. This is purely a difference in which abbreviation is used, with no fundamental difference. Prism includes an equation that fits any EC value directly. All rights reserved. This guide is for an old version of Prism. Browse the latest version or update Prism.
What is the EC50? The IC50 In many experiments, you vary the concentration of an inhibitor. Scroll Prev Top Next More.Half maximal effective concentration EC 50 refers to the concentration of a drug, antibody or toxicant which induces a response halfway between the baseline and maximum after a specified exposure time.
For clarification, a graded dose response curve shows the graded effect of the drug y axis over the dose of the drug x axis in one or an average of subjects. A quantal dose response curve shows the percentage of subjects where a response is noted in an all-or-none manner y axis over the dose of the drug x axis.
For competition binding assays and functional antagonist assays IC 50 is the most common summary measure of the dose-response curve. Biological responses to ligand concentrations typically follow a sigmoidal function. The inflection point at which the increase in response with increasing ligand concentration begins to slow is the EC 50which can be mathematically determined by derivation of the best-fit line. While relying on a graph for estimation is more convenient, this typical method yields less accurate results and less precise.
The response or effect, E, is dependent on both the binding of the drug and the drug-bound receptor.
The agonist that binds to the receptor and initiates the response is usually abbreviated A or D. At low agonist concentrations, [A], the response, E is immeasurably low but at higher [A], E becomes measurable. E increases with [A] until at sufficiently high [A], when E plateaus towards an asymptotic maximum attainable response, E max.
The term "potency" refers to the EC 50 value. There is a wide range of EC 50 values of drugs; they are typically anywhere from nM to mM. Hence, it is often more practical to refer to the logarithmically transformed p EC 50 values instead of EC 50where. A drug's potency is dependent on the drug's affinity and efficacy.
Affinity describes how well a drug can bind to a receptor. Faster or stronger binding is represented by a higher affinity, or equivalently a lower dissociation constant. The EC 50 should not be confused with the affinity constant, K d.
While the former reflects the drug concentration needed for a level of tissue response, the latter reflects the drug concentration needed for an amount of receptor binding.
Efficacy is the relationship between receptor occupancy and the ability to initiate a response at the molecular, cellular, tissue or system level. The EC 50 relates to the Hill equationwhich is a function of the agonist concentration, [A]:. The EC 50 represents the point of inflection of the Hill equation, beyond which increases of [A] have less impact on E.
KD value: a quantitative measurement of antibody affinity
In dose response curvesthe logarithm of [A] is often taken, turning the Hill equation into a sigmoidal logistic function. In this case, the EC 50 represents the rising section of the sigmoid curve. The effects of a stressor or drug generally depend on the exposure time. Therefore, the EC 50 and similar statistics will be a function of exposure time.
The exact shape of this time function will depend upon the stressor e. This time dependency hampers the comparison of potency or toxicity between compounds and between different organisms. A drug will not have a single value of EC 50 due to different tissues having different sensitivities to the drug in part due to tissue specific receptor expression.
From Wikipedia, the free encyclopedia. Pharmacological Reviews. Retrieved Archived from the original on Antagonist Competitive antagonist Irreversible antagonist Physiological antagonist Inverse agonist Enzyme inhibitor. Drug Neurotransmitter Agonist-antagonist Pharmacophore. Mechanism of action Mode of action Binding Receptor biochemistry Desensitization pharmacology.Let's say you are trying to measure the potency of toxin. For Kd 50you are not measuring the whole population, but you are just looking at the receptors of a single person.
In terms of receptors, you have the drug that is supposed to bind to a certain receptors. The chemicals from the drug are floating in your blood. You have receptors on the cell membrane. Drugs need to bind to the receptor to have the function. Trending News. Hailey Bieber endorses Biden — while dad backs Trump. Trump turns power of state against his political rivals. Beware of appropriation posing as a costume.
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EC50 is not equal to KD when tissues have spare receptors. Sandra Lv 4. Still have questions? Get your answers by asking now.The concepts of IC50 and EC50 are fundamental to pharmacology. The EC50 is the concentration of a drug that gives half-maximal response.
The IC50 is the concentration of an inhibitor where the response or binding is reduced by half. Seems simple enough. The rest of this article is about IC50 I for inhibition, for downward sloping dose-response curves.
All the ideas can be applied to stimulatory curves and EC50 E for effective as well. Just stand on your head when you view the figures. The green symbols show measurements made with controls. The data of the experimental dose-response curve red dots extend all the way between the two control values. When fitting this curve, you need to decide how to fit the top plateau of the curve. You have three choices:. The results will be very similar with any of these methods, because the data form a complete dose-response curve with a clear top plateau that is indistinguishable from the blank.
I prefer the third method, as it analyzes all the data, but that is not a strong preference. This figure shows an unusual situation where the inhibition curve plateaus well above the control values NS defined by a high concentration of a standard drug.
This leads to alternative definitions of IC Clearly, a single value cannot summarize such a curve. You'd need at least two values, one to quantify the middle of the curve the drug's potency and one to quantify how low it gets the drug's maximum effect. The relative IC50 is by far the most common definition, and the adjective relative is usually omitted.
50% of what? How exactly are IC50 and EC50 defined?
The NS values are totally ignored with this definition of IC This definition is the one upon which classical pharmacological analysis of agonist and antagonist interactions is based. With appropriate consideration of the biological system and concentrations of interacting ligands, estimated Kd values can often be derived from the IC50 value defined this way not so for the "so-called absolute IC50" mentioned below.
The individual measurements for each mouse MAb K D value may have been developed using a number of various methods and approaches. K D and affinity are inversely related.
The K D value relates to the concentration of antibody the amount of antibody needed for a particular experiment and so the lower the K D value lower concentration and thus the higher the affinity of the antibody.
The measurements were undertaken as a collaboration with J. Landry and X. Zhu, Dept. Read the details of this novel approach for measuring antibody K D. Affinity is the strength of binding of a single molecule to its ligand. It is typically measured and reported by the equilibrium dissociation constant K Dwhich is used to evaluate and rank order strengths of bimolecular interactions.
The binding of an antibody to its antigen is a reversible process, and the rate of the binding reaction is proportional to the concentrations of the reactants. James Landry and Dr. This is a micro-array based system combined with a label-free optical scanner based on polarization-modulated oblique-incidence reflectivity difference OI-RD reference.
Is is EC50 equal to Kd?
In this experiment, the antigen was captured to the solid support in duplicate. The comparative analysis is summarized in table 2 and figure 2. The results indicate excellent correlation, within an order of magnitude, between the analysis methods.
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