Half-maximal inhibitory concentration

Another important kinetic parameter usually determined is the value of IC50, defined as the half maximal inhibitory concentration that provides an indication of the potency of an inhibitor under certain the specific conditions of an evaluation. This parameter is typically determined from dose-response plots in which the percentage conversation or inhibition is plotted against the logarithmic concentration of inhibitor employed in each evaluation. The parallel nature of the /.tPLC system described in this chapter is ideal for the evaluation of this parameter. 

ICso half maximal inhibitory concentration of a substance... 

If enzymes are described under tbe aspect of reaction mechanisms, the maximal rate of turnover Vmax. the Michaelis and Menten constant Km, the half maximal inhibitory concentration ICso, and tbe specific enzyme activity are keys of characterization of the biocatalyst. Even though enzymes are not catalysts in a strong chemical sense, because they often undergo an alteration of structure or chemical composition during a reaction cycle, theory of enzyme kinetics follows the theory of chemical catalysis. 

IC50 or half-maximal inhibitory concentration Concentration required to inhibit a given bioiogioai prooess by haif. 

Cytotoxicity is denoted by inhibition of human epidermal carcinoma (KB-16), human lung adenocarcinoma (A549), human colon carcinoma (HT-29), and murine lymphocytic leukemia (P-388) cells at half maximal inhibitory concentration (IC50) values of pg/mL. bFor the cell lines tested, an IC50 value of <4 pg/mL is regarded as active. 

Platelets were preincubated with DMSO (0.5%, control) or each compound at 37 °C for 3 minutes, and the inducer [arachidonic acid (AA), collagen, platelet-activating factor (PAF), or thrombin] was added. bActivity denoted by antiplatelet aggregation at IC50 (half maximal inhibitory concentration) values of <300 pM. 

Erythrocytes do not contain mitochondria and any anion-sensitive ATPase activity in a particulate fraction must therefore be attributed to the plasma membrane. An Mg-ATPase, which could be stimulated by bicarbonate was found in rabbit erythrocyte membranes [31-33] and should thus be plasma-membrane bound. The properties of the enzyme in rabbit erythrocyte membranes are, however, completely different from those of the anion-sensitive ATPase from other tissues. Whereas sulfite is a good stimulant for the Mg-ATPase in mitochondrial and microsomal fractions of various tissues, it only slightly stimulates [32] or even inhibits [33] the erythrocyte enzyme. Other oxy-anions inhibit the ATPase of erythrocyte membranes [32]. The substrate dependence of the enzyme is greatly different from that of the enzyme from other tissues [32,33]. The half maximal inhibitory concentration of... 

Ethanol and aqueous extracts of passionflower inhibited GABA transaminase and glutamic acid decarboxylase in vitro. The half-maximal inhibitory concentration (IC50) values were between 1.2 and 2.5 mg/ml (Awad et al. 2007). 

The bioactivities generally modelled are half maximal inhibitory concentration (ICjg), minimum inhibitory concentration (MIC) and half maximal effective concentration (ECjg) obtained in biological assays statistical methods used in QSAR studies are principal component analysis, partial least squares, Kohonen neural network, artificial neural network, etc. [3],... 

Bioanalytical support for DDI assays with EC-MS is distinctively different from support for most other ADME screens in that only the probe metabolite (instead of all test compounds) is monitored in all samples. As a result, no MS/MS method optimization (other than that for the probe metabolite) is needed. On the other hand, the EC-MS/MS sample burden for CYP inhibition assays is probably the heaviest among all in vitro ADME screening assays, as CYP assays are typically conducted in 384-well plates and involve full IC50 (half maximal inhibitory concentration) curves, and many times in a time-dependent fashion to measure inhibition potentials for both the test compound and its metabohte(s). As a result, bioanalytical research for CYP inhibition support has mostly focused on improving sample analysis speed and throughput. (Data handling and report generation are now mostly automated and do not represent a bottle neck.) Several assay and bioanalytical approaches used either individually or in combination have been reported for CYP inhibition sample analysis. One approach is to incubate multiple substrates for multiple isozymes in the same well, and use an SRM method with multiple MS/MS transitions to analyze all the metabolites and assess the inhibition... 

Half-maximal-inhibitory-concentration (IC50) The concentration of an inhibitor required for a 50% inhibition of activity. 

The first step before interacting with cells consists in determining the nontoxicity of the complex. The WST-1 proliferation assay is widely used for this purpose WST-1 dye (slightly red) is converted into a dark red formazan compound on enzymatic modification this will occur only if cells are alive. The assay is performed after incubation with increasing amounts of the complex to be tested. Cell viability will be tested by the same way, over a period of incubation of more than 24 h. Such an essay has been performed with [Ln2(L )3] complexes and without any effect up to concentrations of 500 J,M. There is no toxicity of the complexes toward cells, which can be expressed as following the half maximal inhibitory concentration /C50 is more than 500 qM. This can be compared to some cyclen-based bioprobes for which /C50 values are around 200 J,M. 

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