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CEP-18770 (CAS 847499-27-8) is a reversible boronic acid-based inhibitor of proteasome chymotrypsin-like activity It specifically targets the proteasome s P2 threonine protease subunit reducing NF- B signaling and the expression of downstream effectors With a reported IC50 of 3 8 nM CEP-18770 induces apoptosis in multiple myeloma cell lines and inhibits osteoclastogenesis and angiogenesis via suppression of RANKL signaling Research supports its potential use in oncology particularly for multiple myeloma showing selective cytotoxicity sparing normal epithelial and bone marrow-derived cells
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Bortezomib (PS-341 CAS number 179324-69-7) is a reversible proteasome inhibitor structurally composed as an N-terminally protected dipeptide (Pyz-Phe-boroLeu) containing pyrazinoic acid phenylalanine and leucine with boronic acid substitution It exerts biological activity primarily by inhibiting proteasomal degradation pathways thereby accumulating pro-apoptotic factors and initiating programmed cell death Bortezomib inhibits proliferation in cell-based assays such as human non-small cell lung cancer H460 cells (IC50 0 1 M) It has clinical approval for relapsed multiple myeloma and mantle cell lymphoma and is widely employed in research to study proteasome-regulated cellular processes and apoptosis signaling pathways
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MLN2238 (CAS number 1072833-77-2) is a dipeptidyl boronic acid derivative designed as a reversible inhibitor of the 5 subunit (chymotrypsin-like activity) of the 20S proteasome with reported IC50 and Ki values of 3 4 nM and 0 93 nM respectively At higher concentrations MLN2238 also targets the proteasome s 1 (caspase-like) and 2 (trypsin-like) subunits In preclinical studies using xenograft and genetically-engineered models of hematologic malignancies MLN2238 exhibited potent antitumor activity promoting apoptosis and suppressing pathways such as NF- B MLN2238 has research applications in oncology particularly against multiple myeloma and lymphoma including in bortezomib-resistant cell lines
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