| Size | Price | Stock | Qty |
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| Targets |
KZR-504 targets the immunoproteasome subunit LMP2 (also known as β1i), which is one of the catalytic subunits of the immunoproteasome. The immunoproteasome is a specialized form of the proteasome that is induced by interferon-γ and plays a key role in generating peptides for MHC class I antigen presentation. KZR-504 inhibits LMP2 with an IC50 of 51 nM, while showing markedly weaker activity on LMP7 (IC50 4.274 µM).
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| ln Vitro |
In vitro, KZR-504 selectively inhibits LMP2 activity in biochemical and cell-based assays. The compound's inhibitory activity is concentration-dependent, with an IC50 of 51 nM for LMP2 and 4.274 µM for LMP7. This strong selectivity profile allows researchers to dissect LMP2-specific functions in antigen processing and immune regulation without significant inhibition of other immunoproteasome subunits. KZR-504 is used in biochemical studies to probe immunoproteasome activity and selectivity.
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| ln Vivo |
Compounded with anti-targets LMP7 and β5, evaluation of LMP2 inhibition in mouse tissues revealed that KZR-504 (compound 12) exhibits potent and selective in vivo effects in all examined tissues (except from the brain) at >1 mg/ >50% target inhibition at doses of kg [1].
In vivo, KZR-504 achieves >50% LMP2 inhibition at doses ≥1 mg/kg across multiple mouse tissues, excluding the brain. This confirms robust tissue target engagement in peripheral organs. The compound's inability to penetrate the brain makes it suitable for studying peripheral immunoproteasome functions without confounding central nervous system effects. KZR-504 is of particular interest for autoimmune disease research, where modulation of the immunoproteasome may reduce pathogenic immune responses. |
| Enzyme Assay |
The non-cellular assay for KZR-504 involves measuring its inhibitory activity against LMP2 using in vitro enzymatic assays. Recombinant immunoproteasome or purified LMP2 is incubated with a fluorogenic peptide substrate in the presence of varying concentrations of KZR-504. The cleavage of the substrate by LMP2 results in an increase in fluorescence, which is monitored over time. The inhibition of enzymatic activity is calculated, and the IC50 is determined from concentration-response curves.
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| Cell Assay |
The cellular assay for KZR-504 involves treating cells (such as human peripheral blood mononuclear cells or cell lines expressing the immunoproteasome) with the compound and measuring its effects on LMP2 activity and antigen presentation. Cells are treated with KZR-504 at various concentrations, and LMP2 activity is measured using a cell-permeable fluorogenic substrate. The effects on MHC class I surface expression and antigen presentation are assessed by flow cytometry and functional T-cell assays.
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| Animal Protocol |
In the in vivo efficacy study, KZR-504 is administered orally to mice at doses ranging from 1 to 10 mg/kg. Target engagement is assessed by measuring LMP2 activity in tissue lysates from various organs (e.g., spleen, liver, kidney) using fluorogenic substrates. Pharmacodynamic studies are performed to determine the duration of inhibition and the optimal dosing schedule. The compound's effects on immune responses are evaluated in models of autoimmune disease.
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| ADME/Pharmacokinetics |
KZR-504 has a molecular weight of 413.42 and a molecular formula of C₂₁H₂₃N₃O₆. The compound is soluble in DMSO. It should be stored under appropriate conditions as specified by the manufacturer. KZR-504 is stable when stored as a powder and should be protected from moisture and light. For in vivo studies, the compound is formulated in suitable vehicles for oral administration.
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| Toxicity/Toxicokinetics |
The toxicological profile of KZR-504 has not been extensively characterized in the published literature. As a selective immunoproteasome inhibitor, it is expected to have a favorable safety profile compared to non-selective proteasome inhibitors, which can cause significant toxicity. However, comprehensive toxicology data are limited, and KZR-504 should be handled with appropriate laboratory safety precautions.
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| References | |
| Additional Infomation |
KZR-504 is a highly selective LMP2 inhibitor that has been developed as a research tool for studying the immunoproteasome. Its strong selectivity for LMP2 over LMP7 makes it a powerful tool for dissecting LMP2-specific roles in antigen processing and immune regulation. KZR-504 is of interest for autoimmune disease research, enabling exploration of immunoproteasome modulation as a strategy to dampen pathogenic immune responses while sparing constitutive proteasome function.
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| Molecular Formula |
C21H23N3O6
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|---|---|
| Molecular Weight |
413.423825502396
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| Exact Mass |
413.158
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| CAS # |
1629052-78-3
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| Related CAS # |
1629052-78-3;
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| PubChem CID |
117611788
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| Appearance |
White to off-white solid powder
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| LogP |
0
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
9
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| Heavy Atom Count |
30
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| Complexity |
771
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| Defined Atom Stereocenter Count |
3
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| SMILES |
O1C[C@]1(C)C([C@H](CC1C=CC=CC=1)NC([C@H](CO)NC(C1=CC=CC(N1)=O)=O)=O)=O
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| InChi Key |
QYDASSGXBXGRBS-CKJXQJPGSA-N
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| InChi Code |
InChI=1S/C21H23N3O6/c1-21(12-30-21)18(27)15(10-13-6-3-2-4-7-13)23-20(29)16(11-25)24-19(28)14-8-5-9-17(26)22-14/h2-9,15-16,25H,10-12H2,1H3,(H,22,26)(H,23,29)(H,24,28)/t15-,16-,21+/m0/s1
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| Chemical Name |
N-((S)-3-Hydroxy-1-(((S)-1-((R)-2-methyloxiran-2-yl)-1-oxo-3-phenylpropan-2-yl)amino)-1-oxopropan-2-yl)-6-oxo-1,6-dihydropyridine-2-carboxamide
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| Synonyms |
KZR-504 KZR 504 KZR504
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: (1). This product requires protection from light (avoid light exposure) during transportation and storage. (2). Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~170 mg/mL (~411.20 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 4.25 mg/mL (10.28 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 42.5 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 4.25 mg/mL (10.28 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 42.5 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 4.25 mg/mL (10.28 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.4188 mL | 12.0942 mL | 24.1885 mL | |
| 5 mM | 0.4838 mL | 2.4188 mL | 4.8377 mL | |
| 10 mM | 0.2419 mL | 1.2094 mL | 2.4188 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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