Virtual screening to identify potent sepiapterin reductase inhibitors

Bioorg Med Chem Lett. 2020 Jan 15;30(2):126793. doi: 10.1016/j.bmcl.2019.126793. Epub 2019 Nov 9.

Abstract

Sepiapterin reductase has been identified as a potential drug target for neuropathic and inflammatory pain. Virtual screening was executed against a publicly available x-ray crystal structure of sepiapterin reductase. A set of structurally diverse and potent sepiapterin reductase inhibitors was identified. This set of compounds with favorable ligand efficiency and lipophilic efficiency are tractable for further optimization. An SAR follow-up library was synthesized based on one of the virtual screening hits exploring SAR.

Keywords: Docking; MOE; Pain; Sepiapterin reductase; Sulfonamides; Virtual screening.

MeSH terms

  • Alcohol Oxidoreductases / antagonists & inhibitors*
  • Alcohol Oxidoreductases / metabolism
  • Binding Sites
  • Drug Evaluation, Preclinical
  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / metabolism
  • High-Throughput Screening Assays
  • Humans
  • Molecular Docking Simulation
  • Protein Structure, Tertiary
  • Structure-Activity Relationship
  • Sulfonamides / chemistry
  • Sulfonamides / metabolism

Substances

  • Enzyme Inhibitors
  • Sulfonamides
  • Alcohol Oxidoreductases
  • sepiapterin reductase