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

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.

• Authors: Osamu Irie, Takatoshi Kosaka, Takeru Ehara, Fumiaki Yokokawa, Takanori Kanazawa, Hajime Hirao, Astuko Iwasaki, Junichi Sakaki, Naoki Teno, Yuko Hitomi, Genji Iwasaki, Hiroaki Fukaya, Kazuhiko Nonomura, Keiko Tanabe, Shinichi Koizumi, Noriko Uchiyama, Stuart J Bevan, Marzia Malcangio, Clive Gentry, Alyson J Fox, Mohammed Yaqoob, Andrew J Culshaw, Allan Hallett
• Journal: Journal of medicinal chemistry (J Med Chem) Vol. 51 Issue 18 Pg. 5502-5 (Sep 25 2008) ISSN: 1520-4804 [Electronic] United States
• PMID: 18754655 (Publication Type: Journal Article)

Chemical References

• Analgesics
• Cysteine Proteinase Inhibitors
• Cathepsins
• cathepsin S

Topics

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