Targeted Cancer Therapy
- Large selection of proteasome inhibitors
- Immunoproteasome-specific inhibitors
- The proteasome is a promising target for treatment of cancer and autoimmune diseases
- Proteasome inhibitor drugs are already approved by FDA as therapeutics for cancer
- The proteasome is the central non-lysosomal protein degrading machinery in the cytoplasm and nucleus of all eukaryotic cells. It is in charge of degrading key proteins in metabolism, cell cycle control, and cell differentiation.
- Proteins are tagged for degradation with a small protein called ubiquitin. The tagging reaction is catalyzed by enzymes called ubiquitin ligases. Once a protein is tagged with a single ubiquitin molecule, this is a signal to other ligases to attach additional ubiquitin molecules. The result is a polyubiquitin chain that is bound by the proteasome, allowing it to degrade the tagged protein (ubiquitin-proteasome system (UPS)). The degradation process yields peptides of about seven to eight amino acids. These peptides then can be further degraded into single amino acids, which can be used by the cell in the synthesis of new proteins.
- The UPS plays a vital role in maintaining protein homeostasis and in regulating numerous cellular processes. The proteasome, a multi-protease complex, is the key component of the UPS and has been validated as a therapeutic target by the FDA's approval of bortezomib (PS341) and carfilzomib. These proteasome inhibitor drugs have substantially improved outcomes in patients with hematological malignancies and are currently investigated for other types of cancer as well as several other diseases.
- Proteasome inhibition leads to a stress response by accumulation of misfolded and redundant proteins in the cell, inducing cell-cycle arrest and apoptosis. The malignant cell in particular is susceptible to proteasome inhibition, even to small changes, because cancer cells are highly proliferative and their protein translation and degradation rate is higher than in normal cells.
- The immunoproteasome is a highly efficient proteolytic machinery derived from the constitutive proteasome by replacement of three catalytic subunits. It is abundantly expressed in immune cells. Oxidative stress and proinflammatory cytokines are stimuli that lead to elevated production of immunoproteasomes.
- The immunoproteasome plays an important role in immune responses, including processing of, e.g., viral proteins for antigen presentation. It degrades foreign proteins into small proteins. These small proteins are further digested into short peptides presented by major histocompatibility complex (MHC) class I molecules. In addition, the immunoproteasome influences inflammatory disease pathogenesis through its ability to regulate T-cell polarization. The immunoproteasome is also expressed in nonimmune cells during inflammation or neoplastic transformation, supporting a role in the pathogenesis of autoimmune diseases and neoplasms.
- ONX-0914, also known as PR-957, is a potent inhibitor of the immunoproteasome with minimal cross-reactivity for the constitutive proteasome. Cell culture and animal studies have shown that ONX-0914 blocks the production of proinflammatory cytokines, including interleukin-6 and 17, indicating possible applications in the treatment of autoimmune diseases such as rheumatoid arthritis, inflammatory bowel disease, and lupus.
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|F1110-UBP||Ixazomib (MLN-2238)||5 mg||125,00|
|F1111-UBP||Ixazomib (MLN-2238)||25 mg||436,00|
|F1300-UBP||Carfilzomib (PR-171)||5 mg||94,00|
|F1301-UBP||Carfilzomib (PR-171)||25 mg||306,00|
|F1410-UBP||ONX-0914 (PR-957)||5 mg||114,00|
|F1411-UBP||ONX-0914 (PR-957)||25 mg||359,00|
- Please see corresponding product page of UBPBio for further proteasome inhibitors
- All prices are in EURO excl. VAT and shipping. Only available in selected countries.