| Field | Specification |
|---|---|
| Target | |
| Alternative names | PR-957 TFA |
| Applications | |
| Molecular weight | |
| Molecular formula | C33H41F3N4O9 |
| Purity | |
| SMILES | |
| Form | Solid |
| Storage | |
| Shipping | |
| Catalog no. (Mfr.) | |
| Main SKU |
Compound Overview
ONX-0914 TFA, also known as PR-957 TFA, is a selective inhibitor of low-molecular-mass polypeptide-7 (LMP7), the chymotrypsin-like subunit of the immunoproteasome; it blocks cytokine production and attenuates the progression of experimental arthritis. It is also a noncompetitive, irreversible inhibitor of the mycobacterial proteasome (Ki = 5.2 μM) and reactivates latent HIV-1 through HSF-1-mediated p-TEFb activation[1][2][3]. It is supplied as a white to off-white solid (C33H41F3N4O9, MW 694.70) at 98.87% purity.
Physical & Chemical Properties
| Molecular Formula | C33H41F3N4O9 |
|---|---|
| Molecular Weight | 694.70 g/mol |
| Purity | 98.87% |
| Appearance | Solid |
| Color | White to off-white |
| SMILES | O=C(N[C@@H](C)C(N[C@@H](CC1=CC=C(OC)C=C1)C(N[C@@H](CC2=CC=CC=C2)C([C@]3(C)OC3)=O)=O)=O)CN4CCOCC4.O=C(O)C(F)(F)F |
| Target | HIV-1 |
| Signaling Pathway | Metabolic Enzyme/Protease; Anti-infection |
| Solubility | In Vitro: DMSO: 100 mg/mL (143.95 mM; Requires sonication; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO) |
| Storage | 4°C, sealed storage, away from moisture. In solvent: -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture). |
| Shipping | Room temperature in continental US; may vary elsewhere. |
Literature Cited
Sources cited in this description and in the In Vitro & In Vivo Data tab. Peer-reviewed publications that used this product are listed under References.
Safety
For Research Use Only. Not for use in diagnostic or therapeutic procedures, and not for human or veterinary use. Handle in accordance with the Safety Data Sheet and your institution's chemical hygiene plan.
In Vitro
| Solvent | Solubility | Notes |
|---|---|---|
| DMSO | 100 mg/mL (143.95 mM) | requires sonication; use freshly opened DMSO (absorbed moisture lowers solubility) |
Aliquot the stock solution and store it at -80°C (up to 6 months) or -20°C (up to 1 month); sealed storage, away from moisture; avoid repeated freeze-thaw cycles.
In Vivo
Choose the formulation that suits the animal model and route of administration; percentages are volume ratios of the final working solution. Start from a clear DMSO stock (see In Vitro above), add the co-solvents one at a time in the order listed, mixing after each addition, and prepare the working solution fresh on the day of dosing. If precipitation or phase separation occurs, gentle warming or sonication can help.
Protocol 1
| Composition | 10% DMSO + 40% PEG300 + 5% Tween-80 + 45% saline |
|---|---|
| Result | ≥ 2.5 mg/mL (3.60 mM); clear solution |
| How to prepare | Gives a clear solution at ≥ 2.5 mg/mL (saturation not determined). For 1 mL of working solution: add 100 μL DMSO stock (25.0 mg/mL) to 400 μL PEG300; then 50 μL Tween-80; then 450 μL saline to bring the volume to 1 mL. Saline: dissolve 0.9 g sodium chloride in ddH2O and make up to 100 mL. |
Protocol 2
| Composition | 10% DMSO + 90% (20% SBE-β-CD in saline) |
|---|---|
| Result | ≥ 2.5 mg/mL (3.60 mM); clear solution |
| How to prepare | Gives a clear solution at ≥ 2.5 mg/mL (saturation not determined). For 1 mL of working solution: add 100 μL DMSO stock (25.0 mg/mL) to 900 μL 20% SBE-β-CD in saline. 20% SBE-β-CD in saline: dissolve 2 g SBE-β-CD powder in 10 mL saline until clear (4°C, store up to one week). |
Protocol 3
| Composition | 10% DMSO + 90% Corn Oil |
|---|---|
| Result | ≥ 2.5 mg/mL (3.60 mM); clear solution |
| How to prepare | Gives a clear solution at ≥ 2.5 mg/mL (saturation not determined). Use with caution if continuous dosing will exceed two weeks. For 1 mL of working solution: add 100 μL DMSO stock (25.0 mg/mL) to 900 μL corn oil. |
Data provided by the manufacturer.
In Vitro
Antigen presentation specific to LMP7 is inhibited by ONX-0914. In mouse splenocytes, ONX-0914 blocks cytokine production, and it also blocks T cell differentiation[1].
In Vivo
In mouse arthritis, ONX-0914 (2-10 mg/kg; i.v.; on days 4, 6 and 8) ameliorates disease[1]. At 2, 6 and 10 mg per kg body weight (i.v.; days 25, 27, 29, 31 and 33), ONX-0914 also elicits a rapid therapeutic response in the CIA (collagen-induced arthritis) model, which is T and B cell–dependent[1].
| Animal Model | Collagen antibody-induced arthritis (CAIA, Arthritis was induced in BALB/c mice with antibodies specific for type II collagen (mAb) and endotoxin)[1] |
|---|---|
| Dosage | 2, 6 or 10 mg per kg body weight |
| Administration | I.v.; treated on days 4, 6 and 8 |
| Result | Blocked disease progression in a dose-dependent manner and completely ameliorated visible signs of disease at the highest dose. |
Data provided by the manufacturer. Numbered citations refer to the Literature Cited list in the product description.
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The immunoproteasome disturbs neuronal metabolism and drives neurodegeneration in multiple sclerosis. Cell 2025 Aug 21;188(17):4567-4585.e32. PMID: 40532699
Immunoproteasome function maintains oncogenic gene expression in KMT2A-complex driven leukemia. Mol Cancer 2023 Dec 4;22(1):196. PMID: 38049829
Differential Optical Imaging of Antigen Presentation Machinery Using Molecular Optical Reporters. Adv Mater 2025 Jul;37(30):e2420393. PMID: 40370186
Limiting cap-dependent translation increases 20S proteasomal degradation and protects the proteomic integrity in autophagy-deficient skeletal muscle. Autophagy 2025 Jun;21(6):1212-1227. PMID: 39878121
Deficient immunoproteasome assembly drives gain of α-synuclein pathology in Parkinson's disease. Redox Biol 2021 Nov:47:102167. PMID: 34662812
Inhibition of p38 MAPK or immunoproteasome overcomes resistance of chronic lymphocytic leukemia cells to Bcl-2 antagonist venetoclax. Cell Death Dis 2022 Oct 8;13(10):860. PMID: 36209148
Targeting the immunoproteasome in hypothalamic neurons as a novel therapeutic strategy for high-fat diet-induced obesity and metabolic dysregulation. J Neuroinflammation 2024 Aug 2;21(1):191. PMID: 39095788
α-Aminoboronic Acid Moieties in Boro Dipeptides Modulate Proteasome Subunit Selectivity and Provide Access to Compounds with Potent Anticancer and Anti-Inflammatory Activity. J Med Chem 2025 Dec 25;68(24):26405-26417. PMID: 41344819
Discovery of selective fragment-sized immunoproteasome inhibitors. Eur J Med Chem 2021 Jul 5:219:113455. PMID: 33894528
Immunoproteasome inhibitor DPLG3 attenuates experimental colitis by restraining NF-κB activation. Biochem Pharmacol 2020 Jul:177:113964.
