The GMO dossiers were examined for the application of the LoC concept for environmentally relevant compounds assessed in the comparative safety assessment.
Eleven of the novel compounds assessed appeared suitable for in vivo assessment as PET tracers.
A number of the compounds assessed in this work have previously been investigated in other cell systems.
The timing of TRAIL-dependent caspase activation was consistent with previous observations with a variety of other TRAIL-sensitizing compounds assessed in ACHN cells11,12,13.
Using this analysis, fingerprints were generated for 14 out of the 15 compounds assessed, however isoproterenol modulated parameters at concentrations above 100-times the clinical total Cmax.
Results showed evidences that, among the three organic compounds assessed, F4H11 is the most suitable candidate to slow down the copper oxidation process.
Our fingerprint analysis of structural cardiotoxins revealed a diverse array of mechanisms, however either ΔΨm or ER integrity were modulated within 10-fold the clinical total Cmax where cardiac damage has been reported for 12 out of 15 compounds assessed, implicating these organelles to be central to the mechanisms of toxicity.
Among four compounds assessed, compound 2 demonstrated highest specific to NSB ratio (2.2).
> > Blood compounds assessed included creatinine, sodium, potassium, chloride, bicarbonate, CPK, TSH and triiodothyronine (T3).
Among the compounds assessed, the two Class 2 compounds, F2738-2186 and F2573-0380, ealsoalslightlytly elevated EGF-dependent Y-EGFR phosphorylation, while the class I compound F0922-0900 slightly reduced this phosphorylation.
