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I am reading the paper "Activity of the bcr-abl kinase inhibitor PD180970" but I don't understand how IC50 works on table 1. Can you tell with simple words and give me an easy example?

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The IC50 is the concentration of an inhibitor at which you observe the half maximal inhibition. See the figure from the Wikipedia:

enter image description here

The IC50 can be seen as a way to measure the effectiveness of an inhibitor on a biological function as an enzyme. In the case of PD180970 you have an inhibitor which inhibits the p210 Bcr-Abl tyrosine kinase. The IC50 is the concentration at which 50% of the kinase is inhibited.

In table 1 different mutations of the tyrosine kinase are tested against the inhibitor to see, if the mutations have an influence on the IC50. This is important as PD180970 is considered as an anti-cancer drug and possible mutations would make it less effective here.

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  • $\begingroup$ Thank u Chris. I have also some questions about this paper. 1)Do you know the weakness of the kinase assay and mtt assay. Maybe there was another experiment which they could do? $\endgroup$
    – Tomy
    Mar 11 '15 at 21:15
  • $\begingroup$ 2) also why in the table 1 the use two assays for check the ic50? it's complicated!! and why the results are different in one mutation? $\endgroup$
    – Tomy
    Mar 11 '15 at 21:17
  • $\begingroup$ They test the activity on the "naked" kinase in vitro and then also the effect of the inhibitor in a cell based assay (MTT assay, in vivo). That the inhibitor works on the kinase alone doesn't necessarily mean it works also very well in the cell. The T315I mutation most likely affects binding of the inhibitor. If this happens not as good, it will dissociate easier and you need a much higher concentration of your inhibitor to show an effect. $\endgroup$
    – Chris
    Mar 11 '15 at 22:00
  • $\begingroup$ ok!!! can you suggest me another experiment, which there is not in this paper, to check their results of imatinib and pd180970? (how about to transfer this cells in mouse?) maybe there is a better method in your opinion? $\endgroup$
    – Tomy
    Mar 11 '15 at 22:22
  • $\begingroup$ No, sorry. For that I am not really deep enough in the field. $\endgroup$
    – Chris
    Mar 11 '15 at 22:29
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The IC50 is the concentration of inhibitor required to reduce the activity of a molecule/protein by one-half. It is the inverse of EC50. Usually inhibition curves looks sigmoidal so the IC50 is the middle point of the S curve. Here an example. (Note that the Y-axis can be pretty much anything, like enzyme activity and the X-axis is the concentration in a logarithmic scale).

Illustration

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