Molecular modelling of LXR binding to evaluate the potential for liver steatosis

www.cosmostox.eu The traditional vision of safety assessment moved towards a new paradigm of toxicology, based on a Mode-of-Action/Adverse Outcome Pathway (MoA/AOP) approach. The MoA/AOP concept relies on the identification of biochemical pathways the perturbation of which results in an adverse effect. In the MoA/AOP framework addressing repeated dose toxicity, the MoA from liver X receptor (LXR) activation to liver steatosis is one of the toxicological processes associated with target organ toxicity that is being defined and documented as a first step in building a "prototype" safety assessment framework1 within the COSMOS project. The molecular initiating event identified in this MoA is the binding to LXR and activation by appropriate ligands.