3 years ago

Integrated in silico–in vitro screening of ovarian cancer peroxisome proliferator-activated receptor-γ agonists against a biogenic compound library

Er-Xia Jia, Li-Ping Wang, Feng-Ying Liu, Shi-Ming Lv, Gui-Lian Zhang, Jing Zhang


In recent years, peroxisome proliferator-activated receptor-γ (PPARγ) activation by selective agonists has been emerged as a new and promising strategy for ovarian cancer therapy and prevention. Here, an integrated screening protocol that combined computational protein–ligand binding analysis and cell-based reporter-gene assay was performed against >180,000 biogenic compounds (primary and secondary metabolites) to discover novel potent PPARγ agonists. The screening integrated empirical non-binder exclusion, high-throughput molecular docking, fast affinity scoring, and molecular dynamics simulations to identify promising candidates. Consequently, 12 hits were tested in vitro, from which one and three compounds were found to have high and moderate agonistic potencies for PPARγ with EC50 values at nanomolar and micromolar levels, respectively. Structural bioinformatics analysis revealed a variety of chemical interactions, such as hydrogen bonds, van der Waals contacts, and hydrophobic forces at PPARγ complex interface with the newly identified agonists, conferring both high stability and strong specificity to PPARγ–agonist binding.

Publisher URL: https://link.springer.com/article/10.1007/s00044-017-2060-1

DOI: 10.1007/s00044-017-2060-1

You might also like
Discover & Discuss Important Research

Keeping up-to-date with research can feel impossible, with papers being published faster than you'll ever be able to read them. That's where Researcher comes in: we're simplifying discovery and making important discussions happen. With over 19,000 sources, including peer-reviewed journals, preprints, blogs, universities, podcasts and Live events across 10 research areas, you'll never miss what's important to you. It's like social media, but better. Oh, and we should mention - it's free.

  • Download from Google Play
  • Download from App Store
  • Download from AppInChina

Researcher displays publicly available abstracts and doesn’t host any full article content. If the content is open access, we will direct clicks from the abstracts to the publisher website and display the PDF copy on our platform. Clicks to view the full text will be directed to the publisher website, where only users with subscriptions or access through their institution are able to view the full article.