Section15:Glossary

From Assay Guidance Wiki

Abs IC50 - The concentration of a test substance that produces an inhibitory effect corresponding to 50% of the dynamic range of the assay as defined by the maximum and minimum controls in the experiment. In contrast to Rel IC50, Abs IC50 is not necessarily the inflection point of the curve.

Bottom - The lower asymptote of a logarithmically derived curve. The Bottom value can be determined with real values or predicted using the logarithm applied to the result data set.

CRC - Concentration-response curve mode. The mode to describe an assay performed with multiple concentrations of a given test substance, which might then render a logarithmically-derived graph curve.

Emin - The maximum activity of an antagonist test substance relative to a reference agonist. This is obtained by first generating a fitted top from a %Inhibition curve and then converting that to the corresponding %Stimulation of the reference agonist curve. The E-min value for antagonist mode should equal the relative efficacy for agonist mode for competitive inhibitors.

Fold Activity - The ratio of biological activity in the presence of an exogenous substance to that in its absence. It is the test compound’s observed response (raw data value) divided by the median of the same plate’s Min wells. This result type is used exclusively with single point assays. If the value is greater than 1, the test compound is likely an agonist. If the calculated value is less than 1, the test compound could be an inverse agonist.

Fold Activity Max - The maximum observed Fold Activity in a concentration response curve whether it was excluded or not. It is the test compound’s observed response (raw data value) divided by the median of the same plate’s Min wells. If the value is greater than 1, the test compound is likely an agonist. If the calculated value is less than 1, the test compound could be an inverse agonist.

Fold Activity Max (FA) - The maximum observed Fold Activity in a concentration response curve whether it was excluded or not. The (FA) indicates that his result type is summarized. Since activity can be detected at different test substance concentrations, the summarized value must be viewed with this knowledge.

Hill Coeff - Derived slope a three or four parameter logistic curve fit. Should not be fixed to any given value without consultation with a statistician. It should not be a negative value except for inverse agonist assays.

Inh - Activity determined for a single point inhibition assay. Unit of Measure is always %.

Inh @ Max Inc - Inhibition observed at the highest included (i.e. not excluded) concentration of a substance tested in a concentration response mode method version regardless of whether it was included in the parametric fit to produce derived results. (see Illustration below)

Inh @ Max Tst - Inhibition observed at the maximum concentration of a substance tested in a concentration response mode method version regardless of whether it was included in the parametric fit to produce derived results. (see Illustration below)

Inh Max - Maximum inhibition produced by any concentration that was included for the application of a curve fit algorithm (see Illustration below)

Inh Max (FA) - Maximum inhibition produced by any concentration that was included for the application of a curve fit algorithm. This result type differs from Inh Max by allowing summarization to occur; the FA is defined as 'for averaging'. Since this result type could yield an average value from multiple test substance concentrations, the value should be used with this knowledge and therefore with caution.

Ki - Result from the Cheng-Prusoff equation or from a slightly modified derivation. This label is used primarily with binding assays (see QB manual for formula) and represents the affinity of a compound for a receptor. Documentation of the formula and any changes to the Cheng-Prusoff should be noted in the assay protocol.

Kb - Result from the Cheng-Prusoff equation or from a slightly modified derivation. This label is used primarily with functional antagonist assays (see QB manual for formula) and represents the affinity of a compound for a receptor. This label doesn’t represent results mechanistically determined via the Schild analysis; rather the label Schild Kb is used in those calculations.

Pot - Potentiation result type for single point mode. Many potentiation assays involve the addition of one or more concentrations of a test substance in the presence of a fixed concentration of the known active substance called the Reference Agonist. In this mode, potentiation is the response produced by the combination of substances minus the response produced by the specific concentration of Reference Agonist alone.

Pot @ Max Inc - Potentiation observed at the highest included concentration of a substance from an analysis of a concentration response curve.

Pot @ Max Tst - Potentiation observed at the maximum concentration of a single substance tested in a concentration response mode method version regardless of whether it was included in the parametric fit to produce derived results.

Pot Max - The maximum potentiation observed for a substance in a single run of a potentiation concentration response mode method regardless of whether it was included in the parametric fit to produce derived results.

Pot - to be added Activity determined for a single point potentiation assay.

Rel AUC - Defined as the ratio of the area under the fitted concentration-response curve for the test compound to the area under the fitted concentration-response curve for the reference compound.

Rel EC50 - The concentration of a test substance that produces a stimulatory effect corresponding to 50% of the activity of that particular substance (i.e. 50% of the difference between top and bottom of fitted curve). It can also be described as the concentration corresponding to the inflection point of the curve.

Rel EC50 Inv - The Relative EC50 of an inverse agonist.

Rel Eff - The maximum activity of a test substance relative to a standard positive control agonist. The result is expressed as percent from the following formula: 100 x Fitted Top of the test substance divided by the Fitted Top of an Agonist control. The agonist control should have a four parameter curve fit with defined lower and upper asymptotes but can have the Bottom fixed to zero in certain cases. The test compounds should have a four parameter curve fit but can have a three parameter fit with the bottom fixed to zero if the data warrants it.

Rel Eff Inv - The maximum activity of a test substance relative to a standard positive control inverse agonist. The result is expressed as percent from the following formula: 100 x Fitted Top of the test substance divided by the Fitted Top of the Inverse Agonist control. The inverse agonist control should have a four parameter curve fit with defined lower and upper asymptotes but can have the Bottom fixed to zero in certain cases. The test compounds should have a four parameter curve fit but can have a three parameter fit with the bottom fixed to zero if the data warrants it.

Rel IC50 - The concentration of a test substance that produces an inhibitory effect corresponding to 50% of the activity of that particular substance (i.e. 50% of the difference between top and bottom of fitted curve). It can also be described as the concentration corresponding to the inflection point of the curve.

Rel Pot Eff - The fitted top of the potentiation curve minus the normalized response to the specific concentration of Reference Agonist alone divided by 100 minus the normalized response to the specific concentration of Reference Agonist alone.

Stim - Activity determined for a single point stimulation assay. Unit of Measure is always %.

Stim @ Max Inc - Stimulation observed at the highest included (i.e. not excluded) concentration of a substance tested in a concentration response mode method version regardless of whether it was included in the parametric fit to produce derived results. (See illustration below)

Stim @ Max Tst - Stimulation observed at the maximum concentration of a substance tested in a concentration response mode method version regardless of whether it was included in the parametric fit to produce derived results. (See illustration below)

Stim Max - Maximum stimulation produced by any concentration that was included for the application of a curve fit algorithm (See illustration below)

Stim Max (FA) - Maximum stimulation produced by any concentration that was included for the application of a curve fit algorithm. This result type differs from Stim Max by allowing summarization to occur; the FA is defined as 'for averaging'. Since this result type could yield an average value from multiple test substance concentrations, the value should be used with this knowledge and therefore with caution.

Schild Kb - A measure of affinity for a competitive antagonist that is calculated using the ratios of equi-active concentrations of a full agonist (most typically EC50 concentrations are used) in the absence and presence of one or more concentrations of the antagonist. See pp. 335-339, Pharmacologic Analysis of Drug-Receptor Intercation, 3rd Ed. by Terry Kenakin.

SP - Single point mode. Assay performed with once concentration of test substance. Common result types used include Inh and Stim. Result values should always include the concentration of the test substance used to determine the activity. Stephenson’s Kp - A measure of affinity for a partial agonist that is calculated through the comparison of equi-active concentrations of a full agonist in the absence and presence of a single concentration of the partial agonist. See pp. 284-286, Pharmacologic Analysis of Drug-Receptor Intercation, 3rd Ed. by Terry Kenakin.

Top - The upper asymptote of a logarithmically derived curve. The Top value can be determined with real values or predicted using the logarithm applied to the result data set.