The identification of novel acid isostere based inhibitors of the VPS10P family sorting receptor Sortilin

Bioorg Med Chem Lett. 2017 Jun 1;27(11):2629-2633. doi: 10.1016/j.bmcl.2017.02.028. Epub 2017 Feb 20.


Using fragment based and structure based drug discovery strategies a series of novel Sortilin inhibitors has been identified. The inhibitors are based on the N-substituted 1,2,3-triazol-4-one/ol heterocyclic template. X-ray crystallography shows that the 1,2,3-triazol-4-one/ol acts as a carboxylic acid isostere, making a bi-dentate interaction with an arginine residue of Sortilin, an interaction which has not been previously characterised for this heterocycle.

MeSH terms

  • Adaptor Proteins, Vesicular Transport / antagonists & inhibitors*
  • Adaptor Proteins, Vesicular Transport / metabolism
  • Binding Sites
  • Crystallography, X-Ray
  • Drug Design
  • Humans
  • Inhibitory Concentration 50
  • Molecular Dynamics Simulation
  • Protein Structure, Tertiary
  • Structure-Activity Relationship
  • Triazoles / chemistry*
  • Triazoles / metabolism


  • Adaptor Proteins, Vesicular Transport
  • Triazoles
  • sortilin