Abstract
The chapter is focused on methods relevant for predictive toxicology and computer-aided drug design (adverse outcome pathway development, pharmacophore modeling, docking, and 3D QSAR analysis) and applied to study interactions between peroxisome proliferator-activated receptor γ (PPARγ) and its ligands. The methods have been combined to develop an integrated in silico approach allowing both to predict potential PPARγ-mediated hepatotoxicity of receptor’s full agonists, thus supporting hazard characterization, and to identify naturally derived antidiabetic triterpenoids potentially acting through PPARγ partial agonism.
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Notes
- 1.
Only in the in vitro systems achieving of a real equilibrium is suggested, since all other experimental settings involve time-dependent changes, due to cross-relation with other biochemical events (e.g., membrane permeation) and dependence of diffusion gradients and transport phenomena.
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Acknowledgments
The authors would like to acknowledge the support of the European Community’s seventh Framework Program (FP7/2007–2013) COSMOS Project under grant agreement no. 266835, the Cosmetics Europe, and the National Science Fund of Bulgaria grant agreement no. DM 01/1/2016.
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Al Sharif, M., Tsakovska, I., Alov, P., Vitcheva, V., Diukendjieva, A., Pajeva, I. (2019). Molecular Modeling Approach to Study the PPARγ–Ligand Interactions. In: Badr, M. (eds) Nuclear Receptors. Methods in Molecular Biology, vol 1966. Humana, New York, NY. https://doi.org/10.1007/978-1-4939-9195-2_22
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