The LeadProfilingScreen is a laboratory equipment product designed for screening and profiling lead content. It provides accurate and reliable measurements of lead concentrations in various sample types. The core function of this device is to determine lead levels without making any interpretations or extrapolations about its intended use.
Example 8
Compound 1 was tested using Eurofins LeadProfilingScreen®, which detects potential adverse activity, additional unexpected activity and relative selectivity and specificity. The screen includes 68 primary molecular targets, including several CNS targets recommended by the EMEA to evaluate drug dependence potential. Compound 1 exhibited<50% inhibition of each target in the LeadProfilingScreen®, at 10 μM (binding).
Example 12
Compound 76 was tested using Eurofins LeadProfilingScreen®, which detects potential adverse activity, additional unexpected activity and relative selectivity and specificity. The screen includes 68 primary molecular targets, including several CNS targets recommended by the EMEA to evaluate drug dependence potential. Compound 76 exhibited <50% inhibition of each target in the LeadProfilingScreen®, at 10 μM (binding) with the exception of human adenosine A2a (50% inhibition at 10 μM).
Compound 76 was further tested using Eurofins Ames Test. The Ames Test is a widely used bacterial assay for the identification of compounds that can produce gene mutations, and it shows a high predictive value with rodent carcinogenicity tests. The Ames Test used four strains of Salmonella with pre-existing mutations that rendered the bacteria unable to synthesize the essential amino-acid histidine, and, as a result, unable to grow in histidine-free medium. If a compound induces mutations in these particular genes, it can restore gene function, allowing the cells to regain the capacity to synthesize histidine and therefore grow in its absence (“reversion assay”). Compound 76 tested clean in this assay, at 5-100 μM.
Finally, compound 76 was tested in a bacterial cytotoxicity assay. Compound 76 tested clean in this assay, at 0.6-100 μM.
Example 12
Compound 76 was tested using Eurofins LeadProfilingScreen®, which detects potential adverse activity, additional unexpected activity and relative selectivity and specificity. The screen includes 68 primary molecular targets, including several CNS targets recommended by the EMEA to evaluate drug dependence potential. Compound 76 exhibited <50% inhibition of each target in the LeadProfilingScreen®, at 10 μM (binding) with the exception of human adenosine A2a (50% inhibition at 10 μM).
Compound 76 was further tested using Eurofins Ames Test. The Ames Test is a widely used bacterial assay for the identification of compounds that can produce gene mutations, and it shows a high predictive value with rodent carcinogenicity tests. The Ames Test used four strains of Salmonella with pre-existing mutations that rendered the bacteria unable to synthesize the essential amino-acid histidine, and, as a result, unable to grow in histidine-free medium. If a compound induces mutations in these particular genes, it can restore gene function, allowing the cells to regain the capacity to synthesize histidine and therefore grow in its absence (“reversion assay”). Compound 76 tested clean in this assay, at 5-100 μM.
Finally, compound 76 was tested in a bacterial cytotoxicity assay. Compound 76 tested clean in this assay, at 0.6-100 μM.
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