![Dose_response_antagonist](https://upload.wikimedia.org/wikipedia/commons/d/d2/Dose_response_antagonist.jpg)
]
Half maximal effective concentration (EC
50) is a measure of the concentration of a drug, antibody or toxicant which induces a
Stimulus%E2%80%93response_model, response halfway between the baseline and maximum after a specified exposure time. More simply, EC
50 can be defined as the ''concentration required to obtain a 50%
..effect'' and may be also written as
sub>50.
It is commonly used as a measure of a drug's
potency
Potency may refer to:
* Potency (pharmacology), a measure of the activity of a drug in a biological system
* Virility
* Cell potency, a measure of the differentiation potential of stem cells
* In homeopathic dilutions, potency is a measure of how ...
, although the use of EC
50 is preferred over that of 'potency', which has been criticised for its vagueness.
[ EC50 is a measure of concentration, expressed in molar units (M), where 1 M is equivalent to 1 mol/ L.
The EC50 of a ''graded'' ]dose response curve
Dose or Dosage may refer to:
Music
* Dose (Gov't Mule album), ''Dose'' (Gov't Mule album), 1998
* Dose (Latin Playboys album), ''Dose'' (Latin Playboys album)
* Dosage (album), ''Dosage'' (album), by the band Collective Soul
* Dose (song), "Dose" ...
therefore represents the concentration of a compound where 50% of its maximal effect is observed.
The EC50 of a ''quantal'' dose response curve represents the concentration of a compound where 50% of the population exhibit a response, after a specified exposure duration.
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 IC50 is the most common summary measure of the dose-response curve. For agonist/stimulator assays the most common summary measure is the EC50.
The EC50 is also related to IC50 which is a measure of a compound's inhibition (50% inhibition).
Calculation of EC50
Biological responses to ligand
In coordination chemistry, a ligand is an ion or molecule (functional group) that binds to a central metal atom to form a coordination complex. The bonding with the metal generally involves formal donation of one or more of the ligand's electr ...
concentrations typically follow a sigmoid
Sigmoid means resembling the lower-case Greek letter sigma (uppercase Σ, lowercase σ, lowercase in word-final position ς) or the Latin letter S. Specific uses include:
* Sigmoid function, a mathematical function
* Sigmoid colon, part of the l ...
al function. The inflection point
In differential calculus and differential geometry, an inflection point, point of inflection, flex, or inflection (British English: inflexion) is a point on a smooth plane curve at which the curvature changes sign. In particular, in the case of ...
at which the increase in response with increasing ligand concentration begins to slow is the EC50, which 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.[Assay Operations for SAR Support](_blank)
NIH Chemical Genomics Center
The response or effect, E, is dependent on both the binding of the drug and the drug-bound receptor. The agonist
An agonist is a chemical that activates a receptor to produce a biological response. Receptors are cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an antagonist blocks the action of the ago ...
that binds to the receptor and initiates the response is usually abbreviated A or D. At low agonist concentrations, the response, E is immeasurably low but at higher E becomes measurable. E increases with until at sufficiently high when E plateaus towards an asymptotic maximum attainable response, Emax. The at which E is 50% of Emax is termed the half maximal effective concentration
]
Half maximal effective concentration (EC50) is a measure of the concentration of a drug, antibody or toxicant which induces a Stimulus%E2%80%93response_model, response halfway between the baseline and maximum after a specified exposure time. Mo ...
and is abbreviated EC50, or rarely sub>50. The term "potency" refers to the EC50 value. The lower the EC50, the less the concentration of a drug is required to produce 50% of maximum effect and the higher the potency. The EC10 and EC90 concentrations to induce 10% and 90% maximal responses are defined similarly.
There is a wide range of EC50 values of drugs; they are typically anywhere from nM to mM. Hence, it is often more practical to refer to the logarithmically transformed pEC50 values instead of EC50, where.
Relation to affinity and efficacy
A drug's potency is dependent on the drug's Dissociation constant#Protein-ligand binding, affinity and efficacy.
Affinity
Affinity
Affinity may refer to:
Commerce, finance and law
* Affinity (law), kinship by marriage
* Affinity analysis, a market research and business management technique
* Affinity Credit Union, a Saskatchewan-based credit union
* Affinity Equity Par ...
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 EC50 should not be confused with the affinity constant, Kd. 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
Efficacy is the relationship between receptor occupancy and the ability to initiate a response at the molecular, cellular, tissue or system level.
Relation to the Hill Equation
The EC50 relates to the Hill equation, which is a function of the agonist concentration,
:[
where E is the observed response or effect above baseline, and nH, the ]Hill coefficient
In biochemistry and pharmacology, the Hill equation refers to two closely related equations that reflect the binding of ligands to macromolecules, as a function of the ligand concentration. A ligand is "a substance that forms a complex with a bio ...
reflects the slope of the curve.EC50 equation
The EC50 represents the point of inflection
In differential calculus and differential geometry, an inflection point, point of inflection, flex, or inflection (British English: inflexion) is a point on a smooth plane curve at which the curvature changes sign. In particular, in the case of ...
of the Hill equation, beyond which increases of have less impact on E. In dose response curves
Dose or Dosage may refer to:
Music
* ''Dose'' (Gov't Mule album), 1998
* ''Dose'' (Latin Playboys album)
* ''Dosage'' (album), by the band Collective Soul
* "Dose" (song), a 2018 song by Ciara
* "Dose", song by Filter from the album '' Short ...
, the logarithm of is often taken, turning the Hill equation into a sigmoidal logistic function
A logistic function or logistic curve is a common S-shaped curve (sigmoid curve) with equation
f(x) = \frac,
where
For values of x in the domain of real numbers from -\infty to +\infty, the S-curve shown on the right is obtained, with the ...
. In this case, the EC50 represents the rising section of the sigmoid curve.
Limitations
The effects of a stressor or drug generally depend on the exposure time. Therefore, the EC50 (and similar statistics) will be a function of exposure time. The exact shape of this time function will depend upon the stressor (e.g., the specific toxicant), its mechanism of action, the organism exposed, etc. This time dependency hampers the comparison of potency
Potency may refer to:
* Potency (pharmacology), a measure of the activity of a drug in a biological system
* Virility
* Cell potency, a measure of the differentiation potential of stem cells
* In homeopathic dilutions, potency is a measure of how ...
or toxicity
Toxicity is the degree to which a chemical substance or a particular mixture of substances can damage an organism. Toxicity can refer to the effect on a whole organism, such as an animal, bacterium, or plant, as well as the effect on a subst ...
between compounds and between different organisms.
A drug will not have a single value of EC50 due to different tissues having different sensitivities to the drug (in part due to tissue specific receptor expression). Furthermore, EC50 is dependent on many factors including species, tissue and cell type and genetics.
See also
* Measures of pollutant concentration Measures of pollutant concentration are used to determine risk assessment in public health.
Industry is continually synthesizing new chemicals, the regulation of which requires evaluation of the potential danger for human health and the environm ...
* Certain safety factor
The therapeutic index (TI; also referred to as therapeutic ratio) is a quantitative measurement of the relative safety of a drug. It is a comparison of the amount of a therapeutic agent that causes the therapeutic effect to the amount that causes ...
* LD50 (median lethal dose)
* Therapeutic index
The therapeutic index (TI; also referred to as therapeutic ratio) is a quantitative measurement of the relative safety of a drug. It is a comparison of the amount of a therapeutic agent that causes the therapeutic effect to the amount that causes ...
References
External links
Determination of IC50 values
Concentration indicators
Pharmacodynamics
Toxicology
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