proteasome

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proteasome

[′prōd·ē·ə‚sōm]
(biochemistry)
A large proteolytic particle found in the cytoplasm and nucleus of all eukaryotic cells that is the site for degradation of most intracellular proteins.
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Our pioneering research points to a central role of the immunoproteasome in regulating immune responses and restoring normal immune surveillance," said John Fowler, co-founder and CEO of Kezar.
In addition to research and development of immunoproteasome inhibitors, Kezar will embark on multiple drug discovery programs targeting protein secretion for the treatment of autoimmunity and cancer.
The immunoproteasome regulates multiple aspects of immune responses and selective inhibitors, such as those under development at Kezar, are well tolerated and highly active in mouse models rheumatoid arthritis, multiple sclerosis, Crohn's disease, and lupus.
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.
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.
ONX0914 was specifically designed to be a potent inhibitor of the immunoproteasome with minimal cross-reactivity for the constitutive proteasome.
These findings also underline the key role played by the immunoproteasome in development of the inflammatory process.
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.
5] in standard proteasomes, which are replaced during de novo biogenesis of immunoproteasomes by immunosubunits [beta]1i, [beta]2i, and [beta]5i, the transcription of which is induced by several cytokines, such as interferon-[gamma] (20).

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