Proliferator-Activated Receptors (PPARs) belong to the class of
nuclear receptors superfamily.
They are ligand-dependent transcriptional factors involved in the
control and expression of several genes implicated in glucidic and lipidic
homeostasis and energetic balance. In humans, three different isoforms have
been identified: PPARα, PPARβ/δ, and PPARγ. They have different tissue distribution
as well as different binding affinity for ligands and recruitment ability of
coactivators and corepressors. PPARα is mostly involved in the control of lipidic catabolism.
PPARβ/δ is ubiquitously distributed, with a physiological profile similar but non
interchangeable with PPARα. PPARγ is expressed in adipose tissue, where it induces
lipogenesis and fat storage, and in skeletal muscle, where it improves insulin sensitivity.
PPARs, therefore, represent valuable therapeutic targets for the treatment of both hyperlipidemia
and insulin resistance in metabolic disorders.
Many efforts have been directed toward the combination, in a unique chemical entity,
of the insulin-sensitizing effect of PPARγ activation with the additional
lipid-modifying activity of other PPAR subtypes.
Therefore, the development of novel selective PPAR modulators, dual and pan PPAR
agonists constitute a promising approach.
We employ several computational techniques to discover novel PPARs
chemotypes and to achieve a deeper understanding of PPARs mechanism of action.
