It is possible to change to calculate the entropy of a particular panel of all important targets, or to assign a weighting factor to each kinase as proposed at Pmax and a weighted entropy. However, this practice should be evaluated. Then it is advisable to make his own fame in biochemical assays KM ATP because it produces IC50 that relate directly to LY2157299 the value ATPindependent Kd. However, in a cellular Ren environment, there is a high concentration of ATP constant and therefore a selective inhibitor with a different biochemical specificity t act in a cell. If the inhibitor is a specificity t for a target with a KM ATP as the average of the plate so that the inhibitor is not reversed in a specific cell. Selectivity t In the cell is also on factors such as cell penetration, and metabolic activity of foreclosure Determined t. Therefore, the selectivity t biochemical profiling panel is only a first step in the development of selective inhibitors.
Another point is that every Ma Acceptance selectivity t Always used is associated with the test panel, and the value of the entropy Prevents change, if a protein AR-42 is added to the plate. Add a protein that does not bind the inhibitor does not affect the value of the entropy. This way There is the discovery of novel inhibitors of targets, for example erf Leads down k Can the idea of inhibitor selectivity t and the value of the entropy. A good example is IP 103, the more selective inhibitor in Table 1, which in the literature as dual PI3 kinase are / mTOR inhibitor, as shown in Table 1 are specific known as PI3 kinase is not included in panel profiling. Au Addition has a kinase inhibitor that affects 2-1 nM by a panel of 10, the same selectivity t like the entropy of a kinase inhibitor that inhibits 2-1 nM in a panel of 100.
But intuitively, the second inhibitor is specific. This shows that it is important to compare scores of entropy Hnlichen plates. Simultaneously, if the results of the various plates to be weighed, as shown in the example, it should not be assumed for the first inhibitor which is inactive against other kinases in the second plate 90. It w Preferable acid, to provide an average Kd where measurements are missing assign. In this case, the first mark inhibitor more entropy Promiskuit t Comparison inhibitor seconds. Lockable End it should be noted that the selectivity t entropy can be applied in many fields. It k Nnte as a useful Ma in studies that try to link from the safety profiles of compounds in vitro properties.
Currently uses this field various types of scores, Promiskuit t that hnlichkeitsergebnis The selectivity Wear t. A robust and not arbitrary metric and entropy selectivity Tk Nnte in the construction of more detailed models of pharmacological compounds Activity Relationship of selectivity t useful. In conclusion, the selectivity t entropy is a useful tool to make sense of large network to make it data profiling. We have demonstrated the use in the characterization of compounds of tools and drug candidates. Many other applications are in areas where a data table is released and the selectivity t To evaluate the reaction is m Possible. In this sense, the entropy is selectivity t General help for studying the selectivity t. Methods of scoring selectivity t To other comparisons between the current methods, we calculated the salt Play Described nde ectivity S and S as above and in Ref fifth