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

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
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 2,800+ scientific posters on ePosters
  • More than 4,000+ 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 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
Genetic Basis of Fatal Flu Side Effect Discovered
A group of people with fatal H1N1 flu died after their viral infections triggered a deadly hyperinflammatory disorder in susceptible individuals with gene mutations linked to the overactive immune response, according to a recent study.
Developing Drug Resistance may be a Matter of Diversity for Tuberculosis
Researchers have probed the bacteria that causes tuberculosis, Mycobacterium tuberculosis, to learn more about how individual bacterial cells change and adapt while in the human body.
Surprising Trait Found in Anti-HIV Antibodies
Scientists at The Scripps Research Institute (TSRI) have new weapons in the fight against HIV.
Some Gut Microbes May Be Keystones of Health
University of Oregon scientists have found that strength in numbers doesn’t hold true for microbes in the intestines. A minority population of the right type might hold the key to regulating good health.
Essential Component of Antiviral Defense Identified
Infectious disease researchers at the University of Georgia have identified a signaling protein critical for host defense against influenza infection.
Single Vaccine for Chikungunya, Related Viruses May be Possible
What if a single vaccine could protect people from infection by many different viruses? That concept is a step closer to reality.
Is Allergy the Price We Pay for Our Immunity to Parasites?
New findings help demonstrate the evolutionary basis for allergy.
Blocking the Transmission Of Malaria Parasites
Vaccine candidate administered for the first time in humans in a phase I clinical trial led by Oxford University’s Jenner Institute, with partners Imaxio and GSK.
Mucus – the First Line of Defence
Researchers reveal the important role of mucus in building a good defence against invaders.
Antibody Targets Key Cancer Marker
University of Wisconsin-Madison researchers have created a molecular structure that attaches to a molecule on highly aggressive brain cancer and causes tumors to light up in a scanning machine.

Skyscraper Banner
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
2,800+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
4,000+ scientific videos