IC₅₀

Half maximal inhibitory concentration (IC₅₀) is a measure of the

Due to the minus sign, higher values of pIC₅₀ indicate exponentially more potent inhibitors. pIC₅₀ is usually given in terms of molar concentration (mol/L, or M), thus requiring IC₅₀ in units of M.^[2]

The IC₅₀ terminology is also used for some behavioral measures in vivo, such as the 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.^[3]

Functional antagonist assay

The IC₅₀ of a drug can be determined by constructing a

IC₅₀ values are very dependent on conditions under which they are measured. In general, a higher concentration of inhibitor leads to lowered agonist activity. 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 if inhibition is competitive.^{[citation needed]}

IC₅₀ and affinity

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 K_d 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

where K_i is the binding affinity of the inhibitor, IC₅₀ is the functional strength of the inhibitor, [S] is fixed substrate concentration and K_m is the Michaelis constant i.e. 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:^[7]

${\displaystyle K_{i}={\frac {{\ce {IC50}}}{{\frac {[A]}{{\ce {EC50}}}}+1}}}$

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, (e.g. substrate and enzyme concentrations) 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 ligand were present.^[5]

The Cheng-Prusoff equation produces good estimates at high agonist concentrations, but over- or under-estimates K_i at low agonist concentrations. In these conditions, other analyses have been recommended.^[7]

See also

• Certain safety factor
• EC₅₀ (half maximal effective concentration)
• LD₅₀
  (median lethal dose)
• K_i (equilibrium constant)

References