A new phenylpyrazoleanilide, y-320, inhibits interleukin 17 production and ameliorates collagen-induced arthritis in mice and cynomolgus monkeys

Pharmaceuticals
Hiroyuki UshioKenji Chiba

Abstract

Interleukin (IL)-15 and IL-17 are thought to play an important role in the pathogenesis of rheumatoid arthritis (RA) because both pro-inflammatory cytokines are found in synovial fluid of RA patients. In this study, we examined the pharmacological profiles of Y-320, a new phenylpyrazoleanilide immunomodulator. Y-320 inhibited IL-17 production by CD4 T cells stimulated with IL-15 with IC50 values of 20 to 60 nM. Oral administration of Y-320 (0.3 to 3 mg/kg) significantly inhibited the development and progression of arthritis and joint destruction with reduction of IL-17 mRNA expression in arthritic joints of type II collagen-induced arthritis (CIA) in DBA/1J mice. Y-320 in combination with anti-murine tumor necrosis factor-α monoclonal antibody showed a synergistic effect on mouse CIA. Moreover, therapeutic treatment with Y-320 (0.3 and 1 mg/kg orally) ameliorated CIA in cynomolgus monkeys. Our results suggest that Y-320, an orally active inhibitor for IL-17 production, provides a useful therapy for RA.

References

Jun 1, 1986·Agents and Actions·W PaskaM Croft
Aug 1, 1988·The Journal of Experimental Medicine·T J YooA H Kang
Jun 1, 1996·The Journal of Experimental Medicine·F FossiezS Lebecque
Feb 1, 1996·Japanese Journal of Pharmacology·H Kamada, K Nakagami
Feb 29, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·M ZiolkowskaW Maslinski
May 9, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·T Nanki, P E Lipsky
Nov 22, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·T NankiP E Lipsky
Dec 20, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·R O WilliamsR N Maini
Nov 6, 2002·The Journal of Biological Chemistry·Sudeepta AggarwalAustin L Gurney
May 2, 2003·Proceedings of the National Academy of Sciences of the United States of America·Susumu NakaeYoichiro Iwakura
Nov 25, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Susumu NakaeYoichiro Iwakura
Mar 31, 2004·Joint, Bone, Spine : Revue Du Rhumatisme·Pierre Miossec
Oct 16, 2004·Immunity·Jay K Kolls, Anders Lindén
Oct 21, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Sylvie Ferrari-LacrazThomas Moll
Jan 20, 2005·The Journal of Experimental Medicine·Claire L LangrishDaniel J Cua
Aug 24, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Erik LubbertsJay K Kolls
Sep 6, 2005·Arthritis and Rheumatism·Bo BaslundIain B McInnes
May 26, 2007·Nature Reviews. Immunology·Iain B McInnes, Georg Schett
May 26, 2010·International Immunology·Yasuhiro MaedaKenji Chiba

❮ Previous
Next ❯

Citations

Nov 7, 2007·Nihon Rinshō Men'eki Gakkai kaishi = Japanese journal of clinical immunology·Kenji Chiba
Feb 23, 2020·Scientific Reports·Barbara Żyżyńska-GranicaKatarzyna Koziak

❮ Previous
Next ❯

Methods Mentioned

BETA
enzyme-linked immunosorbent assay
ELISA
X-ray
PCR

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.

Related Papers

Nihon Rinshō Men'eki Gakkai kaishi = Japanese journal of clinical immunology
Kenji Chiba
Clinical Immunology : the Official Journal of the Clinical Immunology Society
Yuji NozakiMasanori Funauchi
© 2021 Meta ULC. All rights reserved