Corporate Banner
Satellite Banner
Immunology
Scientific Community
 
Become a Member | Sign in
Home>News>This Article
  News
Return

Onyx Pharmaceuticals Announces Cell Publication Demonstrating Selectivity of Immunoproteasome Inhibitor ONX 0914

Published: Friday, March 30, 2012
Last Updated: Friday, March 30, 2012
Bookmark and Share
Article describes the crystal structures of two forms of the proteasome found in mammalian cells.

Two forms are the constitutive proteasome, expressed by the majority of cells in the body, and the immunoproteasome, expressed in cells derived from the bone marrow, including T-cells and B-cells, two types of white blood cells.

In addition, this work includes structural analysis of the binding of ONX 0914, a selective inhibitor of the immunoproteasome being developed by Onyx, to proteasome active sites. These findings demonstrate the selectivity of ONX 0914, Onyx's proprietary compound, and support the rational design of new immunoproteasome-specific and dual-targeting inhibitors for the potential treatment of autoimmune disorders and cancer. The article is titled "Immuno- and Constitutive Proteasome Crystal Structures Reveal Differences in Substrate and Inhibitor Specificity."

"This research demonstrates the molecular basis of the selectivity of ONX 0914 for the immunoproteasome and highlights its potential as a treatment for autoimmune disorders, such as rheumatoid arthritis and lupus. Selective inhibition of the immunoproteasome may provide anti-inflammatory activity while having a minimal effect on the proteasome in other tissues or on normal immune system function," said Christopher J. Kirk, Ph.D., Vice President of Research at Onyx Pharmaceuticals.

Authors included Drs. Eva Huber, Wolfgang Heinemeyer and Michael Groll of the Center for Integrated Protein Science at the Technical University in Munich, Germany; Drs. Michael Basler, Ricarda Schwab and Marcus Groettrup of the University of Constance in Konstanz, Germany; and Dr. Christopher Kirk of Onyx Pharmaceuticals where ONX 0914 is being developed.
About ONX 0914 ONX 0914, currently in preclinical development, is a highly selective immunoproteasome inhibitor with potential treatment applications in autoimmune disorders, such as rheumatoid arthritis, inflammatory bowel disease and lupus.

The proteasome is an intracellular complex present in most cells that mediates the degradation of intracellular proteins, including key components of pathways that contribute to cancer cell growth and immune signaling. It is a proven and validated target for therapeutic intervention in oncology, but the side effect profiles of existing inhibitors have restricted the potential of this target for therapeutic intervention in autoimmune diseases. While the majority of cell types in the body express the standard form of the proteasome called the constitutive proteasome, cells of the immune system express a unique form of the proteasome called the immunoproteasome. An immunoproteasome-specific inhibitor may have the potential to selectively target proteasome function in immune cells, with minimal effects on the proteasome in other cells.

ONX 0914 was specifically designed to be a potent inhibitor of the immunoproteasome with minimal cross-reactivity for the constitutive proteasome. Recent evidence suggests that the immunoproteasome regulates the production of several inflammatory cytokines, including Tumor Necrosis Factor-a (TNF-a), Interleukin-6 (IL-6), IL-17, and IL-23. In preclinical models of rheumatoid arthritis and lupus, ONX 0914 blocked progression of these diseases and was generally well-tolerated. Preclinical studies are underway to evaluate the potential of ONX 0914 in the treatment of a range of autoimmune disorders.


Further Information

Join For Free

Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 3,300+ scientific posters on ePosters
  • More than 4,900+ scientific videos on LabTube
  • 35 community eNewsletters


Sign In



Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into TechnologyNetworks.com you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.


Scientific News
Targeting Autoimmunity
Researchers have developed a strategy to treat a rare autoimmune disease which could lead to treatments of other autoimmune diseases.
Flu Vaccine May Reduce Death Risk of Type 2 Diabetes
New research suggests that a new flu vaccine may reduce probability of type 2 diabetes patients being hospitalised with stroke and heart failure.
Gut Bacteria Older than Human Species
Some bacteria have lived in the human gut since before we were human, suggesting evolution could have a larger role inhuman bacterial makeup.
Evidence of Mosquito Transmitting Zika
A direct link between the Yellow fever mosquito and Zika transmission has been found following investigation into selective mosquito control.
Antibody-Based Drug for Multiple Sclerosis
New antibody-based drug paves the way for new strategies for controlling and treating multiple sclerosis.
Three-Drug Combinations Counter Antibiotic Resistance
Research shows that combinations of three different antibiotics can treat resistant bacteria, even if they are ineffective independently.
Mapping Zika’s Routes to Developing Fetus
UC researchers show how Zika virus travels from a pregnant woman to her fetus, and also identified a drug that could stop it.
Treating HIV with Cancer-Fighting Gene Shows Promise
A type of gene immunotherapy that has shown promising results against cancer could also be used against HIV.
Protein Teams Activate T-Cells
Caltech researchers have discovered T-cell genetic switching is controlled by four proteins acting in a multi-tiered fashion.
'Antigen-Presenting Cell' Defends Against Cancer
Through advanced imaging, researchers have identified cells that encourages increases in immune system cancer defences.
Skyscraper Banner

SELECTBIO Market Reports
Go to LabTube
Go to eposters
 
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
3,300+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
4,900+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FOR FREE!