Navigation Links
Proteolix, Inc. Drug Candidate, PR-957, Prevents Disease Progression in Rheumatoid Arthritis Models by Selective Inhibition of the Immunoproteasome
Date:6/15/2009

Findings Published in Nature Medicine Suggest Broad Implications for the Treatment of Inflammatory and Autoimmune Disorders

SOUTH SAN FRANCISCO, Calif., June 15 /PRNewswire/ -- Proteolix, Inc. announced that in an article published today in Nature Medicine, Proteolix's selective immunoproteasome inhibitor PR-957 was shown to block disease progression in mouse models of rheumatoid arthritis in a dose-dependent manner and to completely eliminate visible signs of disease at the highest dose. The anti-inflammatory effect induced by PR-957 was rapid and long-lasting, lowering expression of multiple inflammatory mediators, including TNF-a and IL-6. Disease regression was evident 24 hours after dosing and a complete amelioration of disease was achieved with a single dose. When compared to anti-TNF-a therapy (etanercept), PR-957 mediated a more rapid resolution of clinical symptoms, including joint inflammation, and was more effective than etanercept in a model of aggressive arthritis.

These data were published in the June 14, 2009 online edition of Nature Medicine and will be published in the upcoming July 2009 print edition in an article titled: A Selective Inhibitor of the Immunoproteasome Subunit LMP7 Blocks Cytokine Production and Attenuates Progression of Experimental Arthritis. The authors of the article included members of the laboratory of Dr. Marcus Groettrup at the University of Constance (Konstanz, Germany) and researchers, led by Dr. Christopher Kirk, at Proteolix, Inc. (South San Francisco, CA), where the drug candidate was discovered and developed.

PR-957 is the first highly selective, small molecule inhibitor of the immunoproteasome. 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. However, a specific form of the proteasome, known as the immunoproteasome, is found in many cells of the immune system. PR-957 selectively targets a subunit of the immunoproteasome, known as LMP7. Inhibition of this subunit results in a decrease of the immune cell signaling cascade and a halt of the production of cytokines associated with autoimmune inflammation, without affecting proteasome function in non-immune cells. As a consequence, PR-957 induces an anti-inflammatory response at doses less than one tenth the Maximum Tolerated Dose (MTD). In contrast, nonselective inhibitors, such as bortezomib and carfilzomib, induce anti-inflammatory responses only at or near their MTD. These findings also underline the key role played by the immunoproteasome in development of the inflammatory process.

"Targeting protein degradation pathways via the proteasome represents a completely novel approach to regulating the immune response. Using a specially designed proprietary assay, our team of researchers was able to discover and optimize a small molecule capable of demonstrating exquisite selectivity for the LMP7 immunoproteasome subunit," said Susan Molineaux, Ph.D., Chief Scientific Officer at Proteolix. "This selective inhibition of the immunoproteasome results in an increased therapeutic margin compared to that achieved with non-selective proteasome inhibitors, and can have dramatic impact on the inflammatory response without risking broad suppression of immune system function."

Proteolix plans to file an Investigational New Drug Application for PR-957 in mid-2010.

"The research published today in Nature Medicine provides a strong rationale for clinical development of PR-957 in rheumatoid arthritis and other inflammatory and autoimmune diseases," said John A. Scarlett, M.D., President and Chief Executive Officer of Proteolix. "Proteolix has now discovered and developed carfilzomib, a proteasome inhibitor in late Phase 2 clinical trials for the treatment of multiple myeloma, PR-047 as an oral proteasome inhibitor also targeted in oncology, and now PR-957 as a strong drug candidate for the treatment of autoimmune disorders. This demonstrates the Company's unique discovery and development capabilities, as well as its leadership in the field of proteasome inhibition."

About Proteolix

Founded in December 2003, Proteolix, Inc. is a privately-held biotechnology company, headquartered in South San Francisco, dedicated to discovering, developing and commercializing novel therapeutics that target protein degradation pathways for cancer and autoimmune diseases. Proteolix's lead product, carfilzomib, is the first in a new class of selective, irreversible proteasome inhibitors. Proteolix is also developing a pipeline of novel proteasome inhibitors, including a selective, oral proteasome inhibitor and a selective immunoproteasome inhibitor. For additional information on Proteolix, please visit www.proteolix.com.

    Contact information
    Media Inquiries:                       All Other Inquiries:
    BCC Partners                           Craig C. Parker
    Karen L. Bergman or Michelle Corral    Senior Vice President, Finance and
    650-575-1509 or 415-794-8662           Corporate Development & Chief
                                           Financial Officer
                                           650-266-2825


'/>"/>
SOURCE Proteolix, Inc.
Copyright©2009 PR Newswire.
All rights reserved

Related medicine technology :

1. Arcion Therapeutics Topical Pain Candidate, ARC-4558, Significantly Reduces Pain Caused by Diabetic Neuropathy
2. NovaBay Pharmaceuticals Announces Lead Anti-infective Product Candidate, NVC-422, Shown to be Effective in Treating Topical Fungal Infection
3. Bionovo Announces Development Plans for Menopausal Hot Flash Drug Candidate, Menerba (MF101), Following FDA Meetings
4. Ardea Biosciences Presents Phase 2a Antiviral Activity Data for Lead HIV Candidate, RDEA806 at XVII International AIDS Conference
5. Ardea Biosciences Reports Additional Positive Phase 2a Results for Lead HIV Candidate, RDEA806, Demonstrating Up to 1.9 Log Reduction in Plasma Viral Load with Once-Daily Dosing
6. Ardea Biosciences Reports Positive Phase 2a Results for Lead HIV Candidate, RDEA806, Demonstrating up to 2.0 Log Reduction in Plasma Viral Load
7. Survival Data for Avicenas Amyotrophic Lateral Sclerosis Drug Candidate, AL-02, to be Presented at 18th International Symposium on ALS/MND
8. Lpath Demonstrates Strong Safety Profile of Lead Drug Candidate, Sphingomab(TM), in Non-Human Primates
9. Quigley Anti-Viral Compound QR448(a) Successfully Prevents Transmission of Infectious Bronchitis in Chickens
10. Data Suggest CEL-SCIs CEL-2000 Vaccine Prevents or Retards Permanent Damage of Rheumatoid Arthritis
11. Replidynes Investigational Antibacterial Agent REP3123 Prevents Toxin Production in Clostridium difficile
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:6/8/2017)... 2017  Less than a month ago, amateur hackers ... companies, including hospital networks, in over 150 countries. ... the largest online extortion attempts ever recorded. With the ... is imperative that providers understand where the risks lie, ... — and many other very real cyber threats.  ...
(Date:6/7/2017)... 7, 2017  Novavax, Inc., (Nasdaq: NVAX ) ... 2 trials of its RSV F protein recombinant nanoparticle vaccine ... have been published in the journal Vaccine ... in prior scientific conferences). The Company previously announced top ... is developing the RSV F Vaccine with the goal of ...
(Date:6/3/2017)... INDIANAPOLIS , June 3, 2017  Eli ... today announced that results from the Phase 3 ... kinase (CDK)4 & 6 inhibitor, in combination with ... treatment with fulvestrant alone in women with hormone-receptor-positive ... advanced breast cancer who have relapsed or progressed ...
Breaking Medicine Technology:
(Date:6/23/2017)... ... 2017 , ... Studies show evidence that carotenoids and antioxidants derived either from ... these patients. , But how often do ophthalmologists and optometrists in Sweden recommend the ... of or with early symptoms of AMD? A study published recently in ...
(Date:6/23/2017)... ... 2017 , ... Everybody has their own personal preference when it comes to ... some people don't like it at all. FindaTopDoc took a look at what makes ... can give readers a taste of their deepest, darkest fantasies and has the ability ...
(Date:6/23/2017)... ... June 23, 2017 , ... Georgia State University will ... 20. , The two-day conference is focused on advancing scientific knowledge about the ... lives and eliminating racial breast cancer-related disparities. The conference theme is “Illuminating Actionable ...
(Date:6/23/2017)... ... June 23, 2017 , ... Ross Insurance ... With the Federal Emergency Management Agency’s (FEMA) recent update of flood zones, more ... 2012, the Biggert-Waters Act was enacted to reflect the actual risk in flood ...
(Date:6/23/2017)... ... June 23, 2017 , ... ... planning services to communities in the greater Chicago metropolitan area, is embarking on ... to underprivileged youth in Chicago. , Founded in 1897, Hephzibah Children’s Association is ...
Breaking Medicine News(10 mins):