Discovery of orally bioavailable cathepsin S inhibitors for the reversal of neuropathic pain

J Med Chem. 2008 Sep 25;51(18):5502-5. doi: 10.1021/jm800839j.

Abstract

Cathepsin S inhibitors are well-known to be an attractive target as immunological therapeutic agents. Recently, our gene expression analysis identified that cathepsin S inhibitors could also be effective for neuropathic pain. Herein, we describe the efficacy of selective cathepsin S inhibitors as antihyperalgesics in a model of neuropathic pain in rats after oral administration.

MeSH terms

  • Administration, Oral
  • Analgesics / administration & dosage
  • Analgesics / pharmacokinetics
  • Analgesics / therapeutic use*
  • Animals
  • Biological Availability
  • Cathepsins / antagonists & inhibitors*
  • Cysteine Proteinase Inhibitors / administration & dosage
  • Cysteine Proteinase Inhibitors / pharmacokinetics
  • Cysteine Proteinase Inhibitors / therapeutic use*
  • Peripheral Nervous System Diseases / drug therapy*
  • Peripheral Nervous System Diseases / enzymology
  • Rats

Substances

  • Analgesics
  • Cysteine Proteinase Inhibitors
  • Cathepsins
  • cathepsin S