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

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

doi:10.1021/jm800839j

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

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. FoxMohammed Yaqoob, Andrew J. Culshaw, Allan Hallett

^*Corresponding author for this work

Research output: Journal Publications and Reviews › RGC 21 - Publication in refereed journal › peer-review

35 Citations (Scopus)

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. © 2008 American Chemical Society.

Original language	English
Pages (from-to)	5502-5505
Journal	Journal of Medicinal Chemistry
Volume	51
Issue number	18
DOIs	https://doi.org/10.1021/jm800839j
Publication status	Published - 25 Sept 2008
Externally published	Yes

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Irie, O., Kosaka, T., Ehara, T., Yokokawa, F., Kanazawa, T., Hirao, H., Iwasaki, A., Sakaki, J., Teno, N., Hitomi, Y., Iwasaki, G., Fukaya, H., Nonomura, K., Tanabe, K., Koizumi, S., Uchiyama, N., Bevan, S. J., Malcangio, M., Gentry, C., ... Hallett, A. (2008). Discovery of orally bioavailable cathepsin S inhibitors for the reversal of neuropathic pain. Journal of Medicinal Chemistry, 51(18), 5502-5505. https://doi.org/10.1021/jm800839j

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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. {\textcopyright} 2008 American Chemical Society.",

author = "Osamu Irie and Takatoshi Kosaka and Takeru Ehara and Fumiaki Yokokawa and Takanori Kanazawa and Hajime Hirao and Astuko Iwasaki and Junichi Sakaki and Naoki Teno and Yuko Hitomi and Genji Iwasaki and Hiroaki Fukaya and Kazuhiko Nonomura and Keiko Tanabe and Shinichi Koizumi and Noriko Uchiyama and Bevan, {Stuart J.} and Marzia Malcangio and Clive Gentry and Fox, {Alyson J.} and Mohammed Yaqoob and Culshaw, {Andrew J.} and Allan Hallett",

year = "2008",

month = sep,

day = "25",

doi = "10.1021/jm800839j",

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Irie, O, Kosaka, T, Ehara, T, Yokokawa, F, Kanazawa, T, Hirao, H, Iwasaki, A, Sakaki, J, Teno, N, Hitomi, Y, Iwasaki, G, Fukaya, H, Nonomura, K, Tanabe, K, Koizumi, S, Uchiyama, N, Bevan, SJ, Malcangio, M, Gentry, C, Fox, AJ, Yaqoob, M, Culshaw, AJ & Hallett, A 2008, 'Discovery of orally bioavailable cathepsin S inhibitors for the reversal of neuropathic pain', Journal of Medicinal Chemistry, vol. 51, no. 18, pp. 5502-5505. https://doi.org/10.1021/jm800839j

TY - JOUR

T1 - Discovery of orally bioavailable cathepsin S inhibitors for the reversal of neuropathic pain

AU - Irie, Osamu

AU - Kosaka, Takatoshi

AU - Ehara, Takeru

AU - Yokokawa, Fumiaki

AU - Kanazawa, Takanori

AU - Hirao, Hajime

AU - Iwasaki, Astuko

AU - Sakaki, Junichi

AU - Teno, Naoki

AU - Hitomi, Yuko

AU - Iwasaki, Genji

AU - Fukaya, Hiroaki

AU - Nonomura, Kazuhiko

AU - Tanabe, Keiko

AU - Koizumi, Shinichi

AU - Uchiyama, Noriko

AU - Bevan, Stuart J.

AU - Malcangio, Marzia

AU - Gentry, Clive

AU - Fox, Alyson J.

AU - Yaqoob, Mohammed

AU - Culshaw, Andrew J.

AU - Hallett, Allan

PY - 2008/9/25

Y1 - 2008/9/25

N2 - 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. © 2008 American Chemical Society.

AB - 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. © 2008 American Chemical Society.

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U2 - 10.1021/jm800839j

DO - 10.1021/jm800839j

M3 - RGC 21 - Publication in refereed journal

C2 - 18754655

SN - 0022-2623

VL - 51

SP - 5502

EP - 5505

JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

IS - 18

ER -

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

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