2. Academic Validation
  3. Discovery of novel, non-acidic mPGES-1 inhibitors by virtual screening with a multistep protocol

Discovery of novel, non-acidic mPGES-1 inhibitors by virtual screening with a multistep protocol

  • Bioorg Med Chem. 2015 Aug 1;23(15):4839-4845. doi: 10.1016/j.bmc.2015.05.045.
Stefan M Noha 1,  Katrin Fischer 2,  Andreas Koeberle 2,  Ulrike Garscha 2,  Oliver Werz 2,  Daniela Schuster 3
Affiliations

Affiliations

  • 1 Computer Aided Molecular Design (CAMD) Group, Institute of Pharmacy/Pharmaceutical Chemistry, University of Innsbruck, Innrain 80/82, A-6020 Innsbruck, Austria.
  • 2 Chair of Pharmaceutical/Medicinal Chemistry, Institute of Pharmacy, University of Jena, Philosophenweg 14, D-07743 Jena, Germany.
  • 3 Computer Aided Molecular Design (CAMD) Group, Institute of Pharmacy/Pharmaceutical Chemistry, University of Innsbruck, Innrain 80/82, A-6020 Innsbruck, Austria. Electronic address: Daniela.Schuster@uibk.ac.at.
PMID: 26088337 DOI: 10.1016/j.bmc.2015.05.045
Abstract

Microsomal prostaglandin E2 synthase-1 (mPGES-1) inhibitors are considered as potential therapeutic agents for the treatment of inflammatory pain and certain types of Cancer. So far, several series of acidic as well as non-acidic inhibitors of mPGES-1 have been discovered. Acidic inhibitors, however, may have issues, such as loss of potency in human whole blood and in vivo, stressing the importance of the design and identification of novel, non-acidic chemical scaffolds of mPGES-1 inhibitors. Using a multistep virtual screening protocol, the Vitas-M compound library (∼1.3 million entries) was filtered and 16 predicted compounds were experimentally evaluated in a biological assay in vitro. This approach yielded two molecules active in the low micromolar range (IC50 values: 4.5 and 3.8 μM, respectively).

Keywords

3D pharmacophore; Inflammation; Kruskal–Wallis test; Virtual screening; mPGES-1.

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