Ligand- and structure-based drug design strategies and PPARδ/α selectivity

Chem Biol Drug Des. 2012 Oct;80(4):533-44. doi: 10.1111/j.1747-0285.2012.01424.x. Epub 2012 Jul 12.

Abstract

Peroxisome-proliferator-activated receptors are a class of nuclear receptors with three subtypes: α, γ and δ. Their main function is regulating gene transcription related to lipid and carbohydrate metabolism. Currently, there are no peroxisome-proliferator-activated receptors δ drugs being marketed. In this work, we studied a data set of 70 compounds with α and δ activity. Three partial least square models were created, and molecular docking studies were performed to understand the main reasons for peroxisome-proliferator-activated receptors δ selectivity. The obtained results showed that some molecular descriptors (log P, hydration energy, steric and polar properties) are related to the main interactions that can direct ligands to a particular peroxisome-proliferator-activated receptors subtype.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Drug Design*
  • Humans
  • Least-Squares Analysis
  • Ligands
  • Molecular Docking Simulation
  • Multivariate Analysis
  • PPAR alpha / agonists
  • PPAR alpha / chemistry
  • PPAR alpha / metabolism*
  • PPAR delta / agonists
  • PPAR delta / chemistry
  • PPAR delta / metabolism*

Substances

  • Ligands
  • PPAR alpha
  • PPAR delta