Development of a potent and selective cell penetrant Legumain inhibitor

Bioorg Med Chem Lett. 2015 Dec 1;25(23):5642-5. doi: 10.1016/j.bmcl.2015.10.001. Epub 2015 Oct 9.

Abstract

This Letter describes the continued SAR exploration of small molecule Legumain inhibitors with the aim of developing a potent and selective in vitro tool compound. Work continued in this Letter explores the use of alternative P2-P3 linker units and the P3 group SAR which led to the identification of 10t, a potent, selective and cellularly active Legumain inhibitor. We also demonstrate that 10t has activity in both cancer cell viability and colony formation assays.

Keywords: Cancer; Cellular active inhibitor; Cyano warhead; Legumain.

MeSH terms

  • Cell Survival / drug effects
  • Cysteine Endopeptidases* / chemistry
  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / pharmacokinetics*
  • Enzyme Inhibitors / pharmacology
  • Inhibitory Concentration 50
  • Molecular Structure

Substances

  • Enzyme Inhibitors
  • Cysteine Endopeptidases
  • asparaginylendopeptidase