Home>>Signaling Pathways>> Ubiquitination/ Proteasome>> Proteasome>>ONX-0914 (PR-957)

ONX-0914 (PR-957) (Synonyms: ONX-0914,PR-957)

Catalog No.GC15778

A selective inhibitor of the β5i (LMP7) subunit of the immunoproteasome

Products are for research use only. Not for human use. We do not sell to patients.

ONX-0914 (PR-957) Chemical Structure

Cas No.: 960374-59-8

Size Price Stock Qty
10mM (in 1mL DMSO)
$101.00
In stock
5mg
$75.00
In stock
10mg
$148.00
In stock
50mg
$330.00
In stock
100mg
$497.00
In stock
200mg
$900.00
In stock

Tel:(909) 407-4943 Email: sales@glpbio.com

Customer Reviews

Based on customer reviews.

  • GlpBio Citations

    GlpBio Citations
  • Bioactive Compounds Premium Provider

    Bioactive Compounds Premium Provider

Sample solution is provided at 25 µL, 10mM.

Product Documents

Quality Control & SDS

View current batch:

Protocol

Cell experiment: [1]

Cell lines

Human peripheral blood mononuclear (PBMC)cells

Preparation method

The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while.Stock solution can be stored below -20°C for several months.

Reaction Conditions

200 nM, 1 hour

Applications

PBMCs were treated with 200 nM ONX-0914 for 1 hour and were exposure to 1 ng/ml LPS for 24 h. Supernatants were analyzed for expression of the inflammatory cytokines. ONX-0914 selectively inhibited LMP7 (> 80%). LMP7 inhibition blocked production of IL-23 by > 90% and of tumor necrosis factor-α (TNF-α) and IL-6 by ~ 50%. Higher concentrations of ONX-0914, which induce inhibition of LMP2 and MECL-1, further decreased secretion of TNF-α and IL-6, suggesting that these subunits have a role in cytokine regulation.

Animal experiment: [1]

Animal models

Collagen antibody–induced arthritis (CAIA) model in BALB/c mice Collagen-induced arthritis (CIA) model in DBA1/J mice

Dosage form

Intravenous injection, 2, 6 and 10 mg per kg body weight

Applications

ONX-0914 blocked disease progression in a dose-dependent manner and completely ameliorated visible signs of disease at the highest dose. Inhibition of LMP7 alone was sufficient to block disease progression, as evidenced by the therapeutic response to PR-957 administered at 2 mg per kg body weight. ONX-0914 treatment also induced a rapid therapeutic response in the T and B cell–dependent CIA model. Immunoproteasome inhibition was associated with a decrease in circulating levels of autoantibodies and collagen oligomeric matrix protein (COMP), a marker for cartilage breakdown.

Other notes

Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.

References:

[1] Muchamuel T, Basler M, Aujay M A, et al. A selective inhibitor of the immunoproteasome subunit LMP7 blocks cytokine production and attenuates progression of experimental arthritis. Nature medicine, 2009, 15(7): 781-787.

Background

ONX-0914, previously known as PR-975, is a potent inhibitor of immunoproteasome, a form of proteasome generating peptides presented on major histocompatibility complex (MHC) class I molecule to cytotixic T cells, which selectively induces conformational changes in the S1 binding pocket of the immunoproteasome subunit β5i (low molecular mass polypeptide 7/LMP7) rather than the constitutive proteasome subunit β5 in human and mouse cells. ONX-0914 is able to block the production of proinflammatory cytokines from human peripheral blood mononuclear cells (PBMCs), activate mouse splenocytes, inhibit IL-17-producing T cells under TH17-polarizing cytokines in vitro, and attenuate disease progression of diabetes, arthritis, and colitis in mouse models.

Reference

[1].Denise Niewerth, Niels E. Franke, Gerrit Jansen, Yehuda G. Assaraf, Johan van Meerloo, Christopher. Kirk, Jeremiah Degenhardt, Janet Anderl, Aaron D. Schimmer, Sonja Zweegman, Valerie de Haas, Terzah M. Horton, Gertjan J.L. Kaspers, and Jacqueline Cloos. Higer ratio immune vs. constitutive proteasome level as novel indicator of sensitivity of pediatric acute leukemia cells to proteasome inhibitors. Haematologica 2013.
[2].Khalid W. Kalim, Michael Basler, Christopher J. Kirk and Marcus Groettrup. Immunoproteasome subunit LMP7 deficiency and inhibition suppresses Th1 and Th17 but enhances regulatory T cell differentiation. J Immunol 2012; 189:4182-4193

Chemical Properties

Cas No. 960374-59-8 SDF
Synonyms ONX-0914,PR-957
Chemical Name (2S)-3-(4-methoxyphenyl)-N-[(2S)-1-(2-methyloxiran-2-yl)-1-oxo-3-phenylpropan-2-yl]-2-[[(2S)-2-[(2-morpholin-4-ylacetyl)amino]propanoyl]amino]propanamide
Canonical SMILES CC(C(=O)NC(CC1=CC=C(C=C1)OC)C(=O)NC(CC2=CC=CC=C2)C(=O)C3(CO3)C)NC(=O)CN4CCOCC4
Formula C31H40N4O7 M.Wt 580.67
Solubility ≥ 29.0335mg/mL in DMSO, ≥ 69 mg/mL in EtOH Storage Store at -20°C
General tips Please select the appropriate solvent to prepare the stock solution according to the solubility of the product in different solvents; once the solution is prepared, please store it in separate packages to avoid product failure caused by repeated freezing and thawing.Storage method and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored at -20°C, please use it within 1 month.
To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time.
Shipping Condition Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request.

Complete Stock Solution Preparation Table

Prepare stock solution
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
  • Molarity Calculator

  • Dilution Calculator

Mass
=
Concentration
x
Volume
x
MW*
 
 
 
**When preparing stock solutions always use the batch-specific molecular weight of the product found on the vial label and MSDS / CoA (available online).

Calculate

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

mg/kg g μL

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO % % Tween 80 % ddH2O
%DMSO %

Calculation results:

Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid 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 master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.

Reviews

Review for ONX-0914 (PR-957)

Average Rating: 5 ★★★★★ (Based on Reviews and 30 reference(s) in Google Scholar.)

5 Star
100%
4 Star
0%
3 Star
0%
2 Star
0%
1 Star
0%
Review for ONX-0914 (PR-957)

GLPBIO products are for RESEARCH USE ONLY. Please make sure your review or question is research based.

Required fields are marked with *

You may receive emails regarding this submission. Any emails will include the ability to opt-out of future communications.