The f value represents drug efficacy; the lower the f value, the greater the favorable impact (often denoted by Emax, or maximal effect). The IC50 value is related to drug potency, which is defined as the quantity of drug required to cause an effect—the lower the IC50 number, the more effective the medicine. A low IC50 means that the drug is able to reach high concentrations inside cells in order to trigger its effect.
Drugs with high IC50 values are not very effective at reaching high concentrations within cells and thus require much higher doses to produce an effect. Drugs with low IC50 values can therefore be used at lower doses than those required by drugs with high IC50 values. This goes hand in hand with reduced side effects and increased treatment effectiveness.
IC50 values are usually determined using laboratory tests on cell cultures. However, it is difficult to translate IC50 values into clinical effects, since drug absorption, distribution, metabolism and excretion are all affected by the presence of other substances in the body. For example, if you take two drugs with different mechanisms of action but equal IC50 values, then they will have equal effects in vitro but may have different outcomes in vivo. In addition, patients may respond differently to treatments due to differences in their genes or hormones. As such, the only way to know for sure whether one drug is more effective than another is to test them out under real-world conditions.
The EC50 value indicates how much of a medicine is required to achieve 50% of the maximal reaction. The lower the EC50, the more powerful the medication. A dose-response curve is used to calculate this number. For example, if 10 micrograms of morphine per milliliter causes a patient pain relief, and 1 milligram of morphine per kilogram of body weight only causes slight discomfort, then the medicine has a very strong effect at one milligram. If 100 micrograms of morphine per milliliter produces the same result, then the medicine has an intermediate effect. If 1 gram of morphine per kilogram fails to produce any effect, then it would be expected that a larger dose might work better. In this case, the medicine has an extremely weak effect at one gram.
Many drugs have a strong effect at doses less than one milligram because they act on certain types of receptors in the brain and spinal cord. If a drug must go through the blood-brain barrier to reach these receptors, however, then higher doses are needed to produce a similar effect. Most medicines have an effective concentration in the blood that is greater than their maximum possible concentration in the brain. This difference is called the blood-brain barrier filter coefficient and it depends on the size of the medicine's molecules. Smaller molecules pass through the barrier more easily.
The EC50 of a medication is the concentration that produces a half-maximal reaction. The IC50 of an inhibitor is the concentration at which the response (or binding) is decreased by half. Thus, the IC50 for inhibitors is one half the value of the EC50.
In general, low-dose medications have high IC50 values while high-dose medications have low IC50 values. For example, the IC50 of aspirin is approximately 1 mM, while the dose of aspirin used to treat pain is usually between 100 and 400 mg. The IC50 of caffeine is about 110 mM, while the dose of caffeine used to treat fatigue is usually between 200 and 400 mg. Caffeine inhibits the action of cyclic adenosine monophosphate (cAMP), so caffeine cannot be used to treat asthma or allergies because it does not work through cAMP.
High-dose medications can cause problems when taking them over a long period of time. If you take more of something than necessary, you will need less of it later. When this happens with drugs, we call this drug tolerance. Tolerance to drugs can lead to needing higher and higher doses to get the same effect, which can be dangerous if the patient takes too much.
The IC50 value is a quantitative measure that specifies how much of a certain inhibitory substance (e.g., drug) is required to inhibit a given biological process or biological component by 50% in vitro. An enzyme, cell, cell receptor, or microbe might be the biological component. The lower the IC50 value, the more potent is the inhibitor.
There are two main reasons for using an IC50 value: first, to compare the potency of different inhibitors against the same target; second, as a reference point for determining the strength of a biological response to an inhibitor.
For example, an IC50 value of 10 μM means that the inhibitor needs to be present at a concentration of 1 micromole per liter (μL) of culture medium to reduce the rate of cell division by 50%. This would not have any effect on a control sample without the inhibitor added to it. However, if the concentration of the inhibitor was increased to 20 μM, then the rate of cell division would be reduced by almost half (i.e., less than 50%). Thus, a low IC50 value indicates that the inhibitor is very potent.
An IC50 value can also be used to determine the sensitivity of a target to an inhibitor. For example, let's say that the IC50 value for an inhibitor against your target protein is 100 nM.