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The results also support a search for additional compounds preventing HMGB1 release selectively to treat inflammatory diseases.
To search for additional compounds we adopted a less stringent but still significant cut off value of p < 0.05 for our ranking analysis across the two experiments.
Drug class specific signatures of cytotoxicity, which could indicate possible shared mechanisms, have been identified and replicated in both cell lines from different populations and for additional compounds (Watson et al. 2011).
This enabled us (i) to improve the significance for some QTL detected after a simple scan (such as for ethyl octanoate), (ii) to detect a genetic effect for additional compounds (ethyl hexanoate) of one region already found and (iii) to detect three and one additional genomic regions in experiments A and B, respectively, for other compounds.
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Taken together, the structures establish a framework for the development of additional compounds targeting E1 enzymes, which will display higher potency and selectivity.
In the process of curating data we have added an additional 18 targets/mechanisms as well as a number of additional compounds for other recent targets of interest such as MmpL3 which should help balance the bias towards targets that are over represented like InhA.
A number of additional compounds were selected for testing, all with different substituents around a core isoquinolinone.
For additional clarity we now mention in greater detail the mechanism of action for these additional compounds.
The current paper details the expansion of the analytical method to include CYA, AMD and AMN, and results of the analysis of the original infant formula samples (purchased in 2008) for these additional compounds.
Assays ranked high on the reproducibility scale (Table 3) could be prioritized for the scaled-up screening of additional compound libraries.
Table S2 shows raw Ki data for the current study combined with data collected from the literature for the ten additional compounds; a total of thirty-five drugs and sixty-seven receptransportersorters and ion channels which were assayed.
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