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Purity: ≥98%
ONX-0914 (also known as ONX0914; PR957) is a selective LMP7 and LMP2 inhibitor subunits of immunoproteasomes with the potential to be used in autoimmune diseases including rheumatoid arthritis, inflammatory bowel disease and lupus. In an assay without cells, it exhibits negligible cross-reactivity with the constitutive proteasome.
| Targets |
LMP7 (IC50 ~10 nM)
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| ln Vitro |
ONX-0914 is 20- to 40-fold more selective for LMP7 than β5 or LMP2, the next most sensitive sites. LMP7-specific, MHC-I-restricted antigen presentation is blocked in vitro and in vivo by ONX-0914 with little to no cross-reactivity with the constitutive proteasome. The production of interleukin-23 (IL-23) by activated monocytes and interferon-gamma and IL-2 by T cells is inhibited by the selective inhibition of LMP7 by ONX-0914. The inhibition of LMP7 reduces the synthesis of IL-23 by approximately 90% and that of TNF-α and IL-6 by approximately 50%.[1]
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| ln Vivo |
At well-tolerated dosages, ONX-0914 treatment decreases cellular infiltration, cytokine production, and autoantibody levels in mice models of lupus and rheumatoid arthritis while also reversing disease symptoms. In mice, 30 mg/kg body weight is the maximum tolerated dose (MTD) of ONX-0914. Around 60% of ONX-0914's LMP7-selective concentrations and 90% of its higher concentrations inhibit IFN-g release. Moreover, IL-2 production is reduced by about 50%.[1]
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| Cell Assay |
PBMCs were exposed to 1 ng/ml LPS for 24 hours after receiving an hour-long treatment with 200 nM ONX-0914. We examined the expression of the inflammatory cytokines in supernatants. LMP7 was specifically inhibited (> 80%) by ONX-0914. The inhibition of LMP7 resulted in a >90% reduction in the production of IL-23 and a ~50% reduction in the production of TNF-α and IL-6. Greater amounts of ONX-0914, which inhibit LMP2 and MECL-1, further reduced TNF-α and IL-6 secretion, indicating a potential function for these subunits in cytokine regulation.
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| Animal Protocol |
collagen antibody–induced arthritis (CAIA) and collagen-induced arthritis (CIA)
2, 6 or 10 mg/kg i.v. |
| References |
| Molecular Formula |
C31H40N4O7
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|---|---|
| Molecular Weight |
580.67
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| Exact Mass |
580.29
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| Elemental Analysis |
C, 64.12; H, 6.94; N, 9.65; O, 19.29
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| CAS # |
960374-59-8
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| Related CAS # |
ONX-0914 TFA
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| Appearance |
white to off-white solid powder
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| SMILES |
C[C@@H](C(=O)N[C@@H](CC1=CC=C(C=C1)OC)C(=O)N[C@@H](CC2=CC=CC=C2)C(=O)[C@]3(CO3)C)NC(=O)CN4CCOCC4
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| InChi Key |
WQAVPPWWLLVGFK-VTNASVEKSA-N
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| InChi Code |
/C31H40N4O7/c1-21(32-27(36)19-35-13-15-41-16-14-35)29(38)34-26(18-23-9-11-24(40-3)12-10-23)30(39)33-25(28(37)31(2)20-42-31)17-22-7-5-4-6-8-22/h4-12,21,25-26H,13-20H2,1-3H3,(H,32,36)(H,33,39)(H,34,38)/t21-,25-,26-,31+/m0/s1
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| Chemical Name |
(2S)-3-(4-methoxyphenyl)-N-[(2S)-1-[(2R)-2-methyloxiran-2-yl]-1-oxo-3-phenylpropan-2-yl]-2-[[(2S)-2-[(2-morpholin-4-ylacetyl)amino]propanoyl]amino]propanamide
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| Synonyms |
ONX0914; PR-957; ONX 0914; PR 957; ONX-0914; PR957
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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 |
| 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) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.17 mg/mL (3.74 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 21.7 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: ≥ 2.17 mg/mL (3.74 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 21.7 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: ≥ 2.17 mg/mL (3.74 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: 2% DMSO+castor oil: 10 mg/mL |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.7221 mL | 8.6107 mL | 17.2215 mL | |
| 5 mM | 0.3444 mL | 1.7221 mL | 3.4443 mL | |
| 10 mM | 0.1722 mL | 0.8611 mL | 1.7221 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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