For research use only. Not for therapeutic Use.
Zetomipzomib (KZR-616) maleate, a first-in-class immunoproteasome inhibitor, selectively targets the LMP7 (IC50: 39/57 nM=hLMP7/mLMP7) and LMP2 (IC50: 131/179 nM=hLMP2/mLMP2) subunits of the immunoproteasome. Zetomipzomib maleate has the potential for the research of multiple autoimmune diseases[1][2].
Zetomipzomib maleate is an immunoproteasome-selective inhibitor[3]. Zetomipzomib maleate also inhibits MECL-1 subunit (IC50=623 nM) and constitutive proteasome β5 subunit (IC50=688 nM). Zetomipzomib maleate maintains LMP7 and LMP2 selective inhibition in MOLT-4 cells. Zetomipzomib maleate (250 nM) shows a comparable cytokine inhibition profile peripheral blood mononuclear cells (PBMC)[1].?
Zetomipzomib maleate (5 mg/kg; i.v.; dosing was repeated on days 6, 8, 11, and 13) shows efficacy in the anticollagen antibody induced arthritis (CAIA) model[1].
| Catalog Number | I045581 |
| CAS Number | 2170983-62-5 |
| Synonyms | (Z)-but-2-enedioic acid;(2S,3R)-N-[(2S)-3-(cyclopenten-1-yl)-1-[(2R)-2-methyloxiran-2-yl]-1-oxopropan-2-yl]-3-hydroxy-3-(4-methoxyphenyl)-2-[[(2S)-2-[(2-morpholin-4-ylacetyl)amino]propanoyl]amino]propanamide |
| Molecular Formula | C34H46N4O12 |
| Purity | ≥95% |
| InChI | InChI=1S/C30H42N4O8.C4H4O4/c1-19(31-24(35)17-34-12-14-41-15-13-34)28(38)33-25(26(36)21-8-10-22(40-3)11-9-21)29(39)32-23(16-20-6-4-5-7-20)27(37)30(2)18-42-30;5-3(6)1-2-4(7)8/h6,8-11,19,23,25-26,36H,4-5,7,12-18H2,1-3H3,(H,31,35)(H,32,39)(H,33,38);1-2H,(H,5,6)(H,7,8)/b;2-1-/t19-,23-,25-,26+,30+;/m0./s1 |
| InChIKey | HVKAUVYFVFFXLW-MTOCQVLVSA-N |
| SMILES | CC(C(=O)NC(C(C1=CC=C(C=C1)OC)O)C(=O)NC(CC2=CCCC2)C(=O)C3(CO3)C)NC(=O)CN4CCOCC4.C(=CC(=O)O)C(=O)O |
| Reference | [1]. Johnson HWB, et al. Required Immunoproteasome Subunit Inhibition Profile for Anti-Inflammatory Efficacy and Clinical Candidate KZR-616 ((2 S,3 R)- N-(( S)-3-(Cyclopent-1-en-1-yl)-1-(( R)-2-methyloxiran-2-yl)-1-oxopropan-2-yl)-3-hydroxy-3-(4-methoxyphenyl)-2-(( S)-2-(2-morpholinoacetamido)propanamido)propenamide). J Med Chem. 2018 Dec 27;61(24):11127-11143. [2]. Muchamuel T, et al. FRI0296 Kzr-616, a selective inhibitor of the immunoproteasome, blocks the disease progression in multiple models of systemic lupus erythematosus (SLE). Annals of the Rheumatic Diseases 2018;77:685. [3]. Xi J, et al. Immunoproteasome-selective inhibitors: An overview of recent developments as potential drugs for hematologic malignancies and autoimmune diseases. Eur J Med Chem. 2019;182:111646. |
