Skip to main content
Advertisement

Main menu

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Special Sections
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • FAQs
    • For Subscribers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • Submit
  • Other Publications
    • Drug Metabolism and Disposition
    • Journal of Pharmacology and Experimental Therapeutics
    • Molecular Pharmacology
    • Pharmacological Reviews
    • Pharmacology Research & Perspectives
    • ASPET

User menu

  • My alerts
  • Log in
  • My Cart

Search

  • Advanced search
Journal of Pharmacology and Experimental Therapeutics
  • Other Publications
    • Drug Metabolism and Disposition
    • Journal of Pharmacology and Experimental Therapeutics
    • Molecular Pharmacology
    • Pharmacological Reviews
    • Pharmacology Research & Perspectives
    • ASPET
  • My alerts
  • Log in
  • My Cart
Journal of Pharmacology and Experimental Therapeutics

Advanced Search

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Special Sections
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • FAQs
    • For Subscribers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • Submit
  • Visit jpet on Facebook
  • Follow jpet on Twitter
  • Follow jpet on LinkedIn
OtherHighlighted Papers

Treating Arthritis through Selective Bruton's Tryrosine Kinase Inhibition

Journal of Pharmacology and Experimental Therapeutics April 2012, 341 (1) 1;
  • Article
  • Info & Metrics
  • eLetters
  • PDF
Loading

Nonreceptor tyrosine kinases, such as Bruton's tyrosine kinase (Btk), regulate the signal transduction of the B-cell antigen (BCR) and Fc (FcR) receptors that are critical in the development of rheumatoid arthritis (RA); therefore, pharmacological inhibition may affect multiple steps in the pathogenesis of RA and represent a useful therapeutic approach. The study by Xu et al. characterized the role of Btk using the novel, selective Btk inhibitor RN486 [6-cyclopropyl-8-fluoro-2-(2-hydroxymethyl-3-{1-methyl-5-[5-(4-methyl-piperazin-1-yl)-pyridin-2-ylamino]-6-oxo-1,6-dihydro-pyridin-3-yl}-phenyl)-2H-isoquinolin-1-one] in rodent and in vitro models of immune hypersensitivity and arthritis. The selective Btk inhibitor RN486 blocked BCR- and FcR-mediated biological and immune responses in both human cellular assays (tumor necrosis factor αproduction and CD69 expression) and rodent models (type I and III hypersensitivity), providing evidence for mechanism-based actions relevant to human diseases. RN486 produced robust efficacy in two standard rodent models of RA at concentrations that effectively block immunoreceptor-mediated pharmacodynamic responses, expression of CD69 in mice and PCA in rats. Together, these data show that Btk is a key regulator of immunoreceptor-mediated responses in both rodents and humans. Because these immunoreceptor-mediated responses are conserved between rodents and humans, and are essential for the development of immune arthritis in both species, they suggest clinical relevance and support the development of selective Btk inhibitors as RA therapeutics.

See article at J Pharmacol Exp Ther 2012, 341:90–103.

  • Copyright © 2012 by The American Society for Pharmacology and Experimental Therapeutics
PreviousNext
Back to top

In this issue

Journal of Pharmacology and Experimental Therapeutics: 341 (1)
Journal of Pharmacology and Experimental Therapeutics
Vol. 341, Issue 1
1 Apr 2012
  • Table of Contents
  • Table of Contents (PDF)
  • About the Cover
  • Index by author
  • Editorial Board (PDF)
  • Front Matter (PDF)
Download PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for sharing this Journal of Pharmacology and Experimental Therapeutics article.

NOTE: We request your email address only to inform the recipient that it was you who recommended this article, and that it is not junk mail. We do not retain these email addresses.

Enter multiple addresses on separate lines or separate them with commas.
Treating Arthritis through Selective Bruton's Tryrosine Kinase Inhibition
(Your Name) has forwarded a page to you from Journal of Pharmacology and Experimental Therapeutics
(Your Name) thought you would be interested in this article in Journal of Pharmacology and Experimental Therapeutics.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
OtherHighlighted Papers

Treating Arthritis through Selective Bruton's Tryrosine Kinase Inhibition

Journal of Pharmacology and Experimental Therapeutics April 1, 2012, 341 (1) 1;

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero

Share
OtherHighlighted Papers

Treating Arthritis through Selective Bruton's Tryrosine Kinase Inhibition

Journal of Pharmacology and Experimental Therapeutics April 1, 2012, 341 (1) 1;
del.icio.us logo Digg logo Reddit logo Twitter logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • Directly Observable Behavioral Effects of Lorcaserin in Rats
  • Magnesium Modifies the Impact of Calcitriol Treatment In Chronic Kidney Disease
  • Minimal Anticipated Biological Effect Level of Anti-CD28 Receptor Antagonist
Show more Highlighted Papers

Similar Articles

Advertisement
  • Home
  • Alerts
Facebook   Twitter   LinkedIn   RSS

Navigate

  • Current Issue
  • Fast Forward by date
  • Fast Forward by section
  • Latest Articles
  • Archive
  • Search for Articles
  • Feedback
  • ASPET

More Information

  • About JPET
  • Editorial Board
  • Instructions to Authors
  • Submit a Manuscript
  • Customized Alerts
  • RSS Feeds
  • Subscriptions
  • Permissions
  • Terms & Conditions of Use

ASPET's Other Journals

  • Drug Metabolism and Disposition
  • Molecular Pharmacology
  • Pharmacological Reviews
  • Pharmacology Research & Perspectives
ISSN 1521-0103 (Online)

Copyright © 2022 by the American Society for Pharmacology and Experimental Therapeutics