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IC₅₀, or the half maximal inhibitory concentration, represents the concentration of an inhibitor that is required for 50% inhibition of its target (i.e. an enzyme, cell, cell receptor or a microorganism). In simpler terms, it measures how much of a particular substance/molecule is needed to inhibit some biological process by 50%. IC₅₀ is commonly used as a measure of drug potency of antagonist drugs 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 comparible to an EC₅₀ for agonist drugs. EC₅₀ also represents the plasma concentration required for obtaining 50% of a maximum effect in vivo.^[1] Image File history File links Broom_icon. ... HIV protease in a complex with the protease inhibitor ritonavir. ... Ribbon diagram of the enzyme TIM, surrounded by the space-filling model of the protein. ... Drawing of the structure of cork as it appeared under the microscope to Robert Hooke from Micrographia which is the origin of the word cell being used to describe the smallest unit of a living organism Cells in culture, stained for keratin (red) and DNA (green) The cell is the... In biochemistry, a receptor is a protein on the cell membrane or within the cytoplasm that binds to a specific factor (a ligand), such as a neurotransmitter, hormone, or other substance, and initiates the cellular response to the ligand. ... A cluster of Escherichia coli bacteria magnified 10,000 times. ... Potency may refer to: Virility Lack of the above: Erectile dysfunction, Infertility or Effeminacy. ... Antagonists In medicine and biology, a receptor antagonist is a ligand that inhibits the function of an agonist and inverse agonist for a specific receptor. ... “FDA” redirects here. ... The term half maximal effective concentration (EC50) refers to the concentration of a drug which induces a response halfway between the baseline and maximum. ... Agonists An agonist is a substance that binds to a receptor and triggers a response in the cell. ...

Determinting IC₅₀ of a drug

Functional antagonist assay

The IC₅₀ of a drug can be determined constructing a dose-resonse curve and examing 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] The Dose-response relationship describes the change in effect on an organism caused by differing levels of exposure (or doses) to a substance. ...

IC₅₀ values are dependent on conditions under which they are measured. For example for enzymes, IC₅₀ value increases as enzyme 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. Adenosine 5-triphosphate (ATP) is a multifunctional nucleotide that is most important as a molecular currency of intracellular energy transfer. ... Competitive inhibition is a form of enzyme inhibition where binding of the inhibitor to the enzyme prevents binding of the substrate and vice versa. ...

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).^[3][2]

IC₅₀ and affinity

IC₅₀ is not a direct indicator of affinity although the two can be related at least for comptetitive agonists and antagonists by the Cheng-Prusoff eqtn.

 Ki=IC50/1+(S/Km) 

where Ki is the binding affinity of the inhibitor, IC₅₀ is the functional strength of the inhibitor, S is substrate concentration and Km is the affinity of the substrate for the enzyme.Whereas the IC₅₀ value for a compound may vary between experiments depending on radioligand concentration, the K_i is an absolute value. K_i 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 radioligand were present.^[3]

See also

• Certain safety factor
• Dose-response relationship
• EC₅₀
• LD₅₀

The Certain Safety Factor is the ratio of the lethal dose to 1% of population to the effective dose to 99% of the population (LD1/ED99). ... The Dose-response relationship describes the change in effect on an organism caused by differing levels of exposure (or doses) to a substance. ... The term EC50 represents the concentration of a compound where 50% of its effect is observed. ... An LD50 test being administered In toxicology, the LD50 or colloquially semilethal dose of a particular substance is a measure of how much constitutes a lethal dose. ...

References

External links

• Online IC50 Calculator