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ONX-0914

Cat. No. M2071
ONX-0914 Structure
Synonym:

PR-957

Size Price Availability Quantity
5mg USD 81  USD90 In stock
10mg USD 135  USD150 In stock
50mg USD 342  USD380 In stock
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Quality Control
Biological Activity

ONX 0914 (formerly PR-957) is an immunoproteasome inhibitor with potential treatment applications in autoimmune disorders, such as rheumatoid arthritis, inflammatory bowel disease and lupus. ONX-0914 (PR-957) has minimal cross-reactivity for the constitutive proteasome. The immunoproteasome regulates the production of several inflammatory cytokines, including Tumor Necrosis Factor-α (TNF-α), Interleukin-6 (IL-6), IL-17 and IL-23. ONX-0914 blocked progression of these diseases at well tolerated doses in preclinical models of rheumatoid arthritis and lupus. Treatment of LMP2(-/-)/MECL-1(-/-) double-deficient mice with ONX-0914 elicited a strong CTL response in lymphocytic choriomeningitis virus-infected mice.

Product Citations
Customer Product Validations & Biological Datas
Source Mol Cell Protomics (2016). Figure 4.ONX-0914 (Cat. No. M2071, Abmole Bioscience)
Method Immunoproteasome Activity Assays
Cell Lines
Concentrations 20μM
Incubation Time 60 min
Results Levels of ubiquitinated proteins in total homogenates and oxidized proteins in cytosolic homogenates (as determined using the OxyBlot procedure, which detects carbonylated proteins) were increased in I79N mice relative to WT and R278C mice, consistent with impaired UPS function.
Protocol
Cell Experiment
Cell lines ALL and AML cells
Preparation method MTT cytotoxicity assay Cytotoxicity of bortezomib, dexamethasone, as well as their combination, and carfilzomib, ONX 0912, ONX 0914, and 5AHQ was determined using the MTT colorimetric dye reduction assay. For the drug combination study, CalcuSyn (Version 1.1.1 1996, Biosoft, Cambridge, UK) software was used to calculate a combination index (CI) based on the median-effect principle, for each drug combination tested.
Concentrations 0~1µM
Incubation time 96h
Animal Experiment
Animal models RIP-GP mice model
Formulation an aqueous solution of 10% (wt/vol) sulfobutylether-b-cyclodextrin and 10 mM sodium citrate (pH 3.5)
Dosages 6 mg per kg body weight for 10 d
Administration a single i.v. bolus
Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)
Species Mouse Rat Rabbit Guinea pig Hamster Dog
Weight (kg) 0.02 0.15 1.8 0.4 0.08 10
Body Surface Area (m2) 0.007 0.025 0.15 0.05 0.02 0.5
Km factor 3 6 12 8 5 20
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.

Chemical Information
Molecular Weight 580.67
Formula C31H40N4O7
CAS Number 960374-59-8
Purity >99%
Solubility DMSO 60 mg/mL
Storage at -20°C
References

The antiviral immune response in mice devoid of immunoproteasome activity.
Basler M, et al. J Immunol. 2011 Dec 1;187(11):5548-57. PMID: 22013127.

Beneficial effect of novel proteasome inhibitors in murine lupus via dual inhibition of type I interferon and autoantibody-secreting cells.
Ichikawa HT, et al. Arthritis Rheum. 2012 Feb;64(2):493-503. PMID: 21905015.

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  Catalog
Abmole Inhibitor Catalog 2017




Keywords: ONX-0914, PR-957 supplier, Proteasome, inhibitors

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