Proteolix, Inc. Drug Candidate, PR-957, Prevents Disease Progression in Rheumatoid Arthritis Models by Selective Inhibition of the Immuno...(idated target for therapeutic interventi...),Health

Date:6/15/2009

idated 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 ot
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SOURCE Proteolix, Inc. Copyright©2009 PR Newswire. All rights reserved

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