2. Academic Validation
  3. Biological evaluation and structural insights for design of subtype-selective peroxisome proliferator activated receptor-α (PPAR-α) agonists

Biological evaluation and structural insights for design of subtype-selective peroxisome proliferator activated receptor-α (PPAR-α) agonists

  • Bioorg Med Chem Lett. 2015 Jan 15;25(2):270-5. doi: 10.1016/j.bmcl.2014.11.052.
Rahul P Gangwal 1,  Mangesh V Damre 1,  Nihar R Das 2,  Shyam S Sharma 2,  Abhay T Sangamwar 3
Affiliations

Affiliations

  • 1 Department of Pharmacoinformatics, National Institute of Pharmaceutical Education and Research (NIPER), Sect-67, S.A.S. Nagar, Punjab 160 062, India.
  • 2 Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Sect-67, S.A.S. Nagar, Punjab 160 062, India.
  • 3 Department of Pharmacoinformatics, National Institute of Pharmaceutical Education and Research (NIPER), Sect-67, S.A.S. Nagar, Punjab 160 062, India. Electronic address: abhays@niper.ac.in.
PMID: 25491112 DOI: 10.1016/j.bmcl.2014.11.052
Abstract

Peroxisome proliferator activated receptors-α (PPAR-α) control the expression of several genes involved in diseases like diabetes, hyperlipidaemia, and inflammatory disorders. Herein, we report the biological evaluation of recently identified hits from pharmacophore based virtual screening. The most potent hits, ZINC17167211, ZINC06472206 and ZINC08438472 showed EC50 values of 0.16, 1.1 and 12.1nM in PPAR-α agonist assay, respectively. Further, comparative docking and molecular dynamics analysis of selective PPAR-α agonists revealed that Thr279, Ala333, Lys358 and Met325 residues play an important role in the selective PPAR-α agonistic activity. The insights from docking and molecular dynamic studies will serve as a guideline for the development of potent and selective PPAR-α agonists.

Keywords

Molecular docking; PPAR-α; Pharmacophore; Virtual screening.

Figures
Products