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{{merge-from|Pic50|date=January 2013}}
 
[[File:Example IC50 curve demonstrating visually how IC50 is derived.png|thumb|Visual demonstration of how to derive IC50 value: Arrange data with inhibition on vertical axis and log(concentration) on horizontal axis; then identify max and min inhibition; then the IC50 is the concentration at which the curve passes through the 50% inhibition level.]]
 
The '''half maximal inhibitory concentration (IC<sub>50</sub>)''' is a measure of the effectiveness of a substance in inhibiting a specific biological or biochemical function. This quantitative measure indicates how much of a particular drug or other substance ([[Enzyme inhibitor|inhibitor]]) is needed to inhibit a given biological process (or component of a process, i.e. an [[enzyme]], [[cell (biology)|cell]], [[cell receptor]] or [[microorganism]]) by half. It is commonly used as a measure of [[Receptor antagonists|antagonist drug]] [[potency (pharmacology)|potency]] in pharmacological research. According to the [[Food and Drug Administration|FDA]], IC<sub>50</sub> represents the concentration of a drug that is required for 50% inhibition ''[[in vitro]]''.<ref name=fda>[http://www.fda.gov/ohrms/dockets/ac/00/slides/3621s1d/sld036.htm IC50 versus EC50<!-- Bot generated title -->]</ref>
It is comparable to an [[half maximal effective concentration|EC<sub>50</sub>]] for [[agonist|agonist drugs]]. EC<sub>50</sub> also represents the plasma concentration required for obtaining 50% of a maximum effect ''[[in vivo]]''.<ref name=fda/>
 
==Determining the IC<sub>50</sub> of a drug==
 
===Functional antagonist assay===
The IC<sub>50</sub> of a drug can be determined by constructing a [[Dose-response relationship|dose-response curve]] and examining the effect of different concentrations of antagonist on reversing agonist activity. IC<sub>50</sub> values can be calculated for a given antagonist by determining the concentration needed to inhibit half of the maximum biological response of the agonist.<ref name=web>[http://www.ncgc.nih.gov/guidance/section3.html NIH Chemical Genomics Center // Assay Guidance // Assay Guidance Manual // Assay Operations for SAR Support<!-- Bot generated title -->]</ref>
 
IC<sub>50</sub> values are very dependent on conditions under which they are measured. In general, the higher the concentration of inhibitor, the more agonist activity will be lowered. IC<sub>50</sub> value increases as agonist concentration increases. Furthermore depending on the type of inhibition other factors may influence IC<sub>50</sub> value; for [[Adenosine triphosphate|ATP]] dependent enzymes IC<sub>50</sub> value has an interdependency with concentration of ATP, especially so if inhibition is all of it [[Competitive inhibition|competitive]]. IC<sub>50</sub> values can be used to compare the potency of two antagonists.
 
===Competition binding assays===
 
In this type of assay, a single concentration of radioligand (usually an agonist) is used in every assay tube. The ligand is used at a low concentration, usually at or below its [[dissociation constant|K<sub>d</sub>]] value. The level of specific binding of the radioligand is then determined in the presence of a range of concentrations of other competing non-radioactive compounds (usually antagonists), in order to measure the potency with which they compete for the binding of the radioligand. Competition curves may also be computer-fitted to a logistic function as described under direct fit.  
 
In this situation the IC<sub>50</sub> is the concentration of competing ligand which displaces 50% of the specific binding of the radioligand. The IC<sub>50</sub> value is converted to an absolute inhibition constant K<sub>i</sub> using the Cheng-Prusoff equation (see K<sub>i</sub>).<ref name=web/><ref name=Glaxo>[http://www.pdg.cnb.uam.es/cursos/Barcelona2002/pages/Farmac/Comput_Lab/Guia_Glaxo/chap3c.html Glaxo Wellcome and Science - Global<!-- Bot generated title -->]</ref>
 
====IC<sub>50</sub> and affinity====
 
IC<sub>50</sub> is not a direct indicator of affinity although the two can be related at least for competitive agonists and antagonists by the Cheng-Prusoff equation.<ref name="cheng">{{cite journal
|author=Cheng Y, Prusoff WH
|title=Relationship between the inhibition constant (''K<SUB>I</SUB>'') and the concentration of inhibitor which causes 50 per cent inhibition (''I''<SUB>50</SUB>) of an enzymatic reaction
|journal=Biochem Pharmacol
|volume=22
|issue=23
|pages=3099–108
|date=December 1973
|pmid=4202581
|doi=10.1016/0006-2952(73)90196-2
}}</ref> For enzymatic reactions, this equation is:
 
<math> K_i = \frac{IC_{50}}{1+\frac{[S]}{K_m}} </math>
 
where K<sub>i</sub> is the binding affinity of the inhibitor, IC<sub>50</sub> is the functional strength of the inhibitor, [S] is fixed substrate concentration and K<sub>m</sub> is the concentration of substrate at which enzyme activity is at half maximal (but is frequently confused with substrate affinity for the enzyme, which it is not).
 
Alternatively, for inhibition constants at cellular receptors:<ref name='Lazareno'>{{cite pmid|8401922}}</ref>
 
<math> K_i = \frac{IC_{50}}{\frac{[A]}{EC_{50}}+1} </math>
 
where [A] is the fixed concentration of agonist and EC<sub>50</sub> is the concentration of agonist that results in half maximal activation of the receptor. Whereas the IC<sub>50</sub> value for a compound may vary between experiments depending on experimental conditions, the K<sub>i</sub> is an absolute value. K<sub>i</sub> is the inhibition constant for a drug; the concentration of competing ligand in a competition assay which would occupy 50% of the receptors if no ligand were present.<ref name=Glaxo/>
 
The Cheng-Prusoff equation produces good estimates at high agonist concentrations, but over- or under-estimates K<sub>i</sub> at low agonist concentrations. In these conditions, other analyses have been recommended.<ref name='Lazareno' />
 
===pIC<sub>50</sub>===
 
Sometimes, IC<sub>50</sub> values are converted to the '''pIC<sub>50</sub>''' scale.
 
<math>pIC_{50} = -log_{10} (IC_{50}) </math>
 
Note the minus sign, which means that higher values of pIC<sub>50</sub> indicate exponentially greater potency.
 
pIC<sub>50</sub> is usually given in terms of  [[molar concentration]] (mol/L, or M). Therefore to obtain a pIC<sub>50</sub>, an IC<sub>50</sub> should be specified in units of M. When IC<sub>50</sub> is expressed in μM or nM, it will need to be converted to M before conversion to pIC<sub>50</sub>.<ref name="stewart">{{cite journal
|author=Stewart MJ, Watson ID
|title=Standard units for expressing drug concentrations in biological fluids
|journal=British Journal of Clinical Pharmacology
|volume=16
|issue=1
|pages=3–7
|year=1983
|doi=10.1111/j.1365-2125.1983.tb02136.x
}}</ref>
 
===Behavioral Assays===
The IC<sub>50</sub> terminology is also used for some behavioral measures in vivo, such as a two bottle fluid consumption test. When animals decrease consumption from the drug-laced water bottle, the concentration of the drug that results in a 50% decrease in consumption is considered the IC<sub>50</sub> for fluid consumption of that drug.<ref>{{cite journal|pmid=8739548|year=1996|last1=Robinson|first1=SF|last2=Marks|first2=MJ|last3=Collins|first3=AC|title=Inbred mouse strains vary in oral self-selection of nicotine|volume=124|issue=4|pages=332–9|journal=Psychopharmacology}}</ref>
 
== See also ==
* [[Certain safety factor]]
* [[Dose-response relationship]]
* [[EC50|EC<sub>50</sub>]] (half maximal effective concentration)
* [[LD50|LD<sub>50</sub>]] (median lethal dose)
 
== References ==
{{Reflist}}
 
== External links ==
* [http://www.ReaderFit.com ELISA IC50/EC50 Online Tool]
* [http://www.sanjeevslab.org/tools.html IC50 to pIC50 calculator]
* [http://www.antimalarial-icestimator.net/ Online tool for analysis of in vitro resistance to antimalarial drugs]
* [http://botdb.abcc.ncifcrf.gov/toxin/kiConverter.jsp IC50-to-Ki converter]
 
[[Category:Pharmacodynamics]]

Latest revision as of 11:44, 20 April 2013

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Visual demonstration of how to derive IC50 value: Arrange data with inhibition on vertical axis and log(concentration) on horizontal axis; then identify max and min inhibition; then the IC50 is the concentration at which the curve passes through the 50% inhibition level.

The half maximal inhibitory concentration (IC50) is a measure of the effectiveness of a substance in inhibiting a specific biological or biochemical function. This quantitative measure indicates how much of a particular drug or other substance (inhibitor) is needed to inhibit a given biological process (or component of a process, i.e. an enzyme, cell, cell receptor or microorganism) by half. It is commonly used as a measure of antagonist drug potency in pharmacological research. According to the FDA, IC50 represents the concentration of a drug that is required for 50% inhibition in vitro.[1] It is comparable to an EC50 for agonist drugs. EC50 also represents the plasma concentration required for obtaining 50% of a maximum effect in vivo.[1]

Determining the IC50 of a drug

Functional antagonist assay

The IC50 of a drug can be determined by constructing a dose-response curve and examining the effect of different concentrations of antagonist on reversing agonist activity. IC50 values can be calculated for a given antagonist by determining the concentration needed to inhibit half of the maximum biological response of the agonist.[2]

IC50 values are very dependent on conditions under which they are measured. In general, the higher the concentration of inhibitor, the more agonist activity will be lowered. IC50 value increases as agonist concentration increases. Furthermore depending on the type of inhibition other factors may influence IC50 value; for ATP dependent enzymes IC50 value has an interdependency with concentration of ATP, especially so if inhibition is all of it competitive. IC50 values can be used to compare the potency of two antagonists.

Competition binding assays

In this type of assay, a single concentration of radioligand (usually an agonist) is used in every assay tube. The ligand is used at a low concentration, usually at or below its Kd value. The level of specific binding of the radioligand is then determined in the presence of a range of concentrations of other competing non-radioactive compounds (usually antagonists), in order to measure the potency with which they compete for the binding of the radioligand. Competition curves may also be computer-fitted to a logistic function as described under direct fit.

In this situation the IC50 is the concentration of competing ligand which displaces 50% of the specific binding of the radioligand. The IC50 value is converted to an absolute inhibition constant Ki using the Cheng-Prusoff equation (see Ki).[2][3]

IC50 and affinity

IC50 is not a direct indicator of affinity although the two can be related at least for competitive agonists and antagonists by the Cheng-Prusoff equation.[4] For enzymatic reactions, this equation is:

where Ki is the binding affinity of the inhibitor, IC50 is the functional strength of the inhibitor, [S] is fixed substrate concentration and Km is the concentration of substrate at which enzyme activity is at half maximal (but is frequently confused with substrate affinity for the enzyme, which it is not).

Alternatively, for inhibition constants at cellular receptors:[5]

where [A] is the fixed concentration of agonist and EC50 is the concentration of agonist that results in half maximal activation of the receptor. Whereas the IC50 value for a compound may vary between experiments depending on experimental conditions, the Ki is an absolute value. Ki is the inhibition constant for a drug; the concentration of competing ligand in a competition assay which would occupy 50% of the receptors if no ligand were present.[3]

The Cheng-Prusoff equation produces good estimates at high agonist concentrations, but over- or under-estimates Ki at low agonist concentrations. In these conditions, other analyses have been recommended.[5]

pIC50

Sometimes, IC50 values are converted to the pIC50 scale.

Note the minus sign, which means that higher values of pIC50 indicate exponentially greater potency.

pIC50 is usually given in terms of molar concentration (mol/L, or M). Therefore to obtain a pIC50, an IC50 should be specified in units of M. When IC50 is expressed in μM or nM, it will need to be converted to M before conversion to pIC50.[6]

Behavioral Assays

The IC50 terminology is also used for some behavioral measures in vivo, such as a two bottle fluid consumption test. When animals decrease consumption from the drug-laced water bottle, the concentration of the drug that results in a 50% decrease in consumption is considered the IC50 for fluid consumption of that drug.[7]

See also

References

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External links

  1. 1.0 1.1 IC50 versus EC50
  2. 2.0 2.1 NIH Chemical Genomics Center // Assay Guidance // Assay Guidance Manual // Assay Operations for SAR Support
  3. 3.0 3.1 Glaxo Wellcome and Science - Global
  4. One of the biggest reasons investing in a Singapore new launch is an effective things is as a result of it is doable to be lent massive quantities of money at very low interest rates that you should utilize to purchase it. Then, if property values continue to go up, then you'll get a really high return on funding (ROI). Simply make sure you purchase one of the higher properties, reminiscent of the ones at Fernvale the Riverbank or any Singapore landed property Get Earnings by means of Renting

    In its statement, the singapore property listing - website link, government claimed that the majority citizens buying their first residence won't be hurt by the new measures. Some concessions can even be prolonged to chose teams of consumers, similar to married couples with a minimum of one Singaporean partner who are purchasing their second property so long as they intend to promote their first residential property. Lower the LTV limit on housing loans granted by monetary establishments regulated by MAS from 70% to 60% for property purchasers who are individuals with a number of outstanding housing loans on the time of the brand new housing purchase. Singapore Property Measures - 30 August 2010 The most popular seek for the number of bedrooms in Singapore is 4, followed by 2 and three. Lush Acres EC @ Sengkang

    Discover out more about real estate funding in the area, together with info on international funding incentives and property possession. Many Singaporeans have been investing in property across the causeway in recent years, attracted by comparatively low prices. However, those who need to exit their investments quickly are likely to face significant challenges when trying to sell their property – and could finally be stuck with a property they can't sell. Career improvement programmes, in-house valuation, auctions and administrative help, venture advertising and marketing, skilled talks and traisning are continuously planned for the sales associates to help them obtain better outcomes for his or her shoppers while at Knight Frank Singapore. No change Present Rules

    Extending the tax exemption would help. The exemption, which may be as a lot as $2 million per family, covers individuals who negotiate a principal reduction on their existing mortgage, sell their house short (i.e., for lower than the excellent loans), or take part in a foreclosure course of. An extension of theexemption would seem like a common-sense means to assist stabilize the housing market, but the political turmoil around the fiscal-cliff negotiations means widespread sense could not win out. Home Minority Chief Nancy Pelosi (D-Calif.) believes that the mortgage relief provision will be on the table during the grand-cut price talks, in response to communications director Nadeam Elshami. Buying or promoting of blue mild bulbs is unlawful.

    A vendor's stamp duty has been launched on industrial property for the primary time, at rates ranging from 5 per cent to 15 per cent. The Authorities might be trying to reassure the market that they aren't in opposition to foreigners and PRs investing in Singapore's property market. They imposed these measures because of extenuating components available in the market." The sale of new dual-key EC models will even be restricted to multi-generational households only. The models have two separate entrances, permitting grandparents, for example, to dwell separately. The vendor's stamp obligation takes effect right this moment and applies to industrial property and plots which might be offered inside three years of the date of buy. JLL named Best Performing Property Brand for second year running

    The data offered is for normal info purposes only and isn't supposed to be personalised investment or monetary advice. Motley Fool Singapore contributor Stanley Lim would not personal shares in any corporations talked about. Singapore private home costs increased by 1.eight% within the fourth quarter of 2012, up from 0.6% within the earlier quarter. Resale prices of government-built HDB residences which are usually bought by Singaporeans, elevated by 2.5%, quarter on quarter, the quickest acquire in five quarters. And industrial property, prices are actually double the levels of three years ago. No withholding tax in the event you sell your property. All your local information regarding vital HDB policies, condominium launches, land growth, commercial property and more

    There are various methods to go about discovering the precise property. Some local newspapers (together with the Straits Instances ) have categorised property sections and many local property brokers have websites. Now there are some specifics to consider when buying a 'new launch' rental. Intended use of the unit Every sale begins with 10 p.c low cost for finish of season sale; changes to 20 % discount storewide; follows by additional reduction of fiftyand ends with last discount of 70 % or extra. Typically there is even a warehouse sale or transferring out sale with huge mark-down of costs for stock clearance. Deborah Regulation from Expat Realtor shares her property market update, plus prime rental residences and houses at the moment available to lease Esparina EC @ Sengkang
  5. 5.0 5.1 Template:Cite pmid
  6. One of the biggest reasons investing in a Singapore new launch is an effective things is as a result of it is doable to be lent massive quantities of money at very low interest rates that you should utilize to purchase it. Then, if property values continue to go up, then you'll get a really high return on funding (ROI). Simply make sure you purchase one of the higher properties, reminiscent of the ones at Fernvale the Riverbank or any Singapore landed property Get Earnings by means of Renting

    In its statement, the singapore property listing - website link, government claimed that the majority citizens buying their first residence won't be hurt by the new measures. Some concessions can even be prolonged to chose teams of consumers, similar to married couples with a minimum of one Singaporean partner who are purchasing their second property so long as they intend to promote their first residential property. Lower the LTV limit on housing loans granted by monetary establishments regulated by MAS from 70% to 60% for property purchasers who are individuals with a number of outstanding housing loans on the time of the brand new housing purchase. Singapore Property Measures - 30 August 2010 The most popular seek for the number of bedrooms in Singapore is 4, followed by 2 and three. Lush Acres EC @ Sengkang

    Discover out more about real estate funding in the area, together with info on international funding incentives and property possession. Many Singaporeans have been investing in property across the causeway in recent years, attracted by comparatively low prices. However, those who need to exit their investments quickly are likely to face significant challenges when trying to sell their property – and could finally be stuck with a property they can't sell. Career improvement programmes, in-house valuation, auctions and administrative help, venture advertising and marketing, skilled talks and traisning are continuously planned for the sales associates to help them obtain better outcomes for his or her shoppers while at Knight Frank Singapore. No change Present Rules

    Extending the tax exemption would help. The exemption, which may be as a lot as $2 million per family, covers individuals who negotiate a principal reduction on their existing mortgage, sell their house short (i.e., for lower than the excellent loans), or take part in a foreclosure course of. An extension of theexemption would seem like a common-sense means to assist stabilize the housing market, but the political turmoil around the fiscal-cliff negotiations means widespread sense could not win out. Home Minority Chief Nancy Pelosi (D-Calif.) believes that the mortgage relief provision will be on the table during the grand-cut price talks, in response to communications director Nadeam Elshami. Buying or promoting of blue mild bulbs is unlawful.

    A vendor's stamp duty has been launched on industrial property for the primary time, at rates ranging from 5 per cent to 15 per cent. The Authorities might be trying to reassure the market that they aren't in opposition to foreigners and PRs investing in Singapore's property market. They imposed these measures because of extenuating components available in the market." The sale of new dual-key EC models will even be restricted to multi-generational households only. The models have two separate entrances, permitting grandparents, for example, to dwell separately. The vendor's stamp obligation takes effect right this moment and applies to industrial property and plots which might be offered inside three years of the date of buy. JLL named Best Performing Property Brand for second year running

    The data offered is for normal info purposes only and isn't supposed to be personalised investment or monetary advice. Motley Fool Singapore contributor Stanley Lim would not personal shares in any corporations talked about. Singapore private home costs increased by 1.eight% within the fourth quarter of 2012, up from 0.6% within the earlier quarter. Resale prices of government-built HDB residences which are usually bought by Singaporeans, elevated by 2.5%, quarter on quarter, the quickest acquire in five quarters. And industrial property, prices are actually double the levels of three years ago. No withholding tax in the event you sell your property. All your local information regarding vital HDB policies, condominium launches, land growth, commercial property and more

    There are various methods to go about discovering the precise property. Some local newspapers (together with the Straits Instances ) have categorised property sections and many local property brokers have websites. Now there are some specifics to consider when buying a 'new launch' rental. Intended use of the unit Every sale begins with 10 p.c low cost for finish of season sale; changes to 20 % discount storewide; follows by additional reduction of fiftyand ends with last discount of 70 % or extra. Typically there is even a warehouse sale or transferring out sale with huge mark-down of costs for stock clearance. Deborah Regulation from Expat Realtor shares her property market update, plus prime rental residences and houses at the moment available to lease Esparina EC @ Sengkang
  7. One of the biggest reasons investing in a Singapore new launch is an effective things is as a result of it is doable to be lent massive quantities of money at very low interest rates that you should utilize to purchase it. Then, if property values continue to go up, then you'll get a really high return on funding (ROI). Simply make sure you purchase one of the higher properties, reminiscent of the ones at Fernvale the Riverbank or any Singapore landed property Get Earnings by means of Renting

    In its statement, the singapore property listing - website link, government claimed that the majority citizens buying their first residence won't be hurt by the new measures. Some concessions can even be prolonged to chose teams of consumers, similar to married couples with a minimum of one Singaporean partner who are purchasing their second property so long as they intend to promote their first residential property. Lower the LTV limit on housing loans granted by monetary establishments regulated by MAS from 70% to 60% for property purchasers who are individuals with a number of outstanding housing loans on the time of the brand new housing purchase. Singapore Property Measures - 30 August 2010 The most popular seek for the number of bedrooms in Singapore is 4, followed by 2 and three. Lush Acres EC @ Sengkang

    Discover out more about real estate funding in the area, together with info on international funding incentives and property possession. Many Singaporeans have been investing in property across the causeway in recent years, attracted by comparatively low prices. However, those who need to exit their investments quickly are likely to face significant challenges when trying to sell their property – and could finally be stuck with a property they can't sell. Career improvement programmes, in-house valuation, auctions and administrative help, venture advertising and marketing, skilled talks and traisning are continuously planned for the sales associates to help them obtain better outcomes for his or her shoppers while at Knight Frank Singapore. No change Present Rules

    Extending the tax exemption would help. The exemption, which may be as a lot as $2 million per family, covers individuals who negotiate a principal reduction on their existing mortgage, sell their house short (i.e., for lower than the excellent loans), or take part in a foreclosure course of. An extension of theexemption would seem like a common-sense means to assist stabilize the housing market, but the political turmoil around the fiscal-cliff negotiations means widespread sense could not win out. Home Minority Chief Nancy Pelosi (D-Calif.) believes that the mortgage relief provision will be on the table during the grand-cut price talks, in response to communications director Nadeam Elshami. Buying or promoting of blue mild bulbs is unlawful.

    A vendor's stamp duty has been launched on industrial property for the primary time, at rates ranging from 5 per cent to 15 per cent. The Authorities might be trying to reassure the market that they aren't in opposition to foreigners and PRs investing in Singapore's property market. They imposed these measures because of extenuating components available in the market." The sale of new dual-key EC models will even be restricted to multi-generational households only. The models have two separate entrances, permitting grandparents, for example, to dwell separately. The vendor's stamp obligation takes effect right this moment and applies to industrial property and plots which might be offered inside three years of the date of buy. JLL named Best Performing Property Brand for second year running

    The data offered is for normal info purposes only and isn't supposed to be personalised investment or monetary advice. Motley Fool Singapore contributor Stanley Lim would not personal shares in any corporations talked about. Singapore private home costs increased by 1.eight% within the fourth quarter of 2012, up from 0.6% within the earlier quarter. Resale prices of government-built HDB residences which are usually bought by Singaporeans, elevated by 2.5%, quarter on quarter, the quickest acquire in five quarters. And industrial property, prices are actually double the levels of three years ago. No withholding tax in the event you sell your property. All your local information regarding vital HDB policies, condominium launches, land growth, commercial property and more

    There are various methods to go about discovering the precise property. Some local newspapers (together with the Straits Instances ) have categorised property sections and many local property brokers have websites. Now there are some specifics to consider when buying a 'new launch' rental. Intended use of the unit Every sale begins with 10 p.c low cost for finish of season sale; changes to 20 % discount storewide; follows by additional reduction of fiftyand ends with last discount of 70 % or extra. Typically there is even a warehouse sale or transferring out sale with huge mark-down of costs for stock clearance. Deborah Regulation from Expat Realtor shares her property market update, plus prime rental residences and houses at the moment available to lease Esparina EC @ Sengkang