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Chemical Structure| 960374-59-8 Chemical Structure| 960374-59-8

Structure of ONX-0914
CAS No.: 960374-59-8

Chemical Structure| 960374-59-8

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ONX-0914 (PR-957) is a selective inhibitor of the chymotrypsin-like subunit of the immunoproteasome, low-molecular mass polypeptide-7 (LMP7). It blocks cytokine production and reduces the progression of experimental arthritis. ONX-0914 is a noncompetitive irreversible inhibitor of the mycobacterial proteasome (Ki = 5.2 μM) and reactivates latent HIV-1 through p-TEFb activation mediated by HSF-1.

Synonyms: PR-957

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Product Details of ONX-0914

CAS No. :960374-59-8
Formula : C31H40N4O7
M.W : 580.67
SMILES Code : O=C(N[C@@H](CC1=CC=CC=C1)C([C@]2(C)OC2)=O)[C@@H](NC([C@@H](NC(CN3CCOCC3)=O)C)=O)CC4=CC=C(OC)C=C4
Synonyms :
PR-957
MDL No. :MFCD26794217

Safety of ONX-0914

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Isoform Comparison

Biological Activity

In Vitro:

Cell Line
Concentration Treated Time Description References
CLU177 cells 10 nM 24 hours To study the effect of ONX-0914 on PA-induced insulin-glucose axis imbalance, results showed that ONX-0914 restored the decrease in AKT phosphorylation caused by PA. PMC11297766
mouse splenocytes 300 nM overnight ONX-0914 reduced the surface expression of H-2Kb PMC6280796
human PBMCs 300 nM overnight ONX-0914 inhibited IL-6 secretion PMC6280796
mouse splenic CD4+ T cells 300 nM 3 days ONX-0914 inhibited Th17 cell differentiation PMC6280796
PC3 cells 300 nM 24 hours To investigate the effect of ONX-0914 on apoptosis of CRPC cells, results showed that ONX-0914 induces CRPC cell apoptosis via activation of the unfolded protein response (UPR). PMC10050322
22Rv.1 cells 300 nM 24 hours To investigate the effect of ONX-0914 on apoptosis of CRPC cells, results showed that ONX-0914 induces CRPC cell apoptosis via activation of the unfolded protein response (UPR). PMC10050322
TRAMP-C2 cells 300 nM 24 hours ONX 0914 induced poly-ubiquitin accumulation in TRAMP-C2 cells and triggered apoptosis via both intrinsic and extrinsic pathways. PMC9757486
DU145 cells 300 nM 24 hours ONX 0914 induced poly-ubiquitin accumulation in DU145 cells and triggered apoptosis via both intrinsic and extrinsic pathways. PMC9757486
Human peripheral blood mononuclear cells (PBMCs) 100 nM 24 hours ONX-0914 reduced the secretion of GM-CSF and IL-23 PMC3927957
Alveolar Macrophages (AMs) 0.2 μM 6 hours To evaluate the inhibitory effect of ONX-0914 on M1 macrophage polarization, results showed that ONX-0914 significantly suppressed the expression of M1 marker genes. PMC11600198
RAW264.7 cells 0.2 μM 6 hours To evaluate the inhibitory effect of ONX-0914 on CSE-induced M1 polarization, results showed that ONX-0914 significantly suppressed the expression of M1 marker genes. PMC11600198

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
Mice DSS-induced colitis subcutaneous injection 10 mg/kg daily for 5 days ONX-0914 protected mice from colitis PMC6280796
Mice CRPC tumor graft model Subcutaneous injection 10 mg/kg Every other day for 8 weeks To investigate the inhibitory effect of ONX-0914 on CRPC tumor progression, results showed that ONX-0914 prevents CRPC progression by suppressing Th17-type inflammatory response and inducing CRPC cell apoptosis. PMC10050322
Mice TRAMP mouse model Subcutaneous injection 10 mg/kg Three times a week for 22 weeks ONX 0914 treatment significantly inhibited prostate cancer growth in TRAMP mice, reduced the frequency of malignant prostatic lesions, and inhibited metastasis formation. PMC9757486
A/J mice Coxsackievirus B3 (CVB3)-induced myocarditis model Subcutaneous injection 10 mg/kg Once daily for 5 days (from day 3 to day 7 post-infection) To investigate the impact of ONX-0914 on myocarditis following CVB3 infection. Results showed that ONX-0914 treatment did not improve cardiac function, and inflammatory responses in heart tissue were unaffected. PMC7851025
Mice LDLr–/– and APOE*3-Leiden.CETP mice Intraperitoneal injection 10 mg/kg 3 times per week for 7 weeks ONX-0914 significantly reduced atherosclerosis, decreased dendritic cell and macrophage levels and their activation, reduced white adipose tissue mass, and improved markers of metabolic syndrome. PMC11188635
Mice Experimental autoimmune encephalomyelitis (EAE) Subcutaneous injection 10 mg/kg Three times per week for 26 days ONX-0914 significantly delayed the onset of EAE and reduced disease severity PMC3927957
Mice LPS/Elastase-induced emphysema model Intranasal administration 5 mg/kg Three times a week for four weeks To evaluate the therapeutic effect of ONX-0914 on emphysema, results showed that ONX-0914 significantly improved lung function and alleviated lung inflammation. PMC11600198

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

1.72mL

0.34mL

0.17mL

8.61mL

1.72mL

0.86mL

17.22mL

3.44mL

1.72mL

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