Home Proteases Proteasome inhibitor ONX-0914 (PR-957) For research use only.

ONX-0914 (PR-957)

ONX-0914 (PR-957) is a potent and selective immunoproteasome inhibitor with minimal cross-reactivity for the constitutive proteasome in a cell-free assay.

ONX-0914 (PR-957) Chemical Structure

ONX-0914 (PR-957) Chemical Structure

CAS No. 960374-59-8

Purity & Quality Control

ONX-0914 (PR-957) Related Products

Signaling Pathway

Proteasome Signaling Pathways

Proteasome Signaling Pathway

Cell Data

Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
Raji Function assay Inhibition of proteasome subunit beta-5i in human Raji cells using BODIPY-NC005 by fluorescent densitometry, IC50=0.0057μM 25006746
EBC1 Antitumor assay 15 mg/kg 5 days Antitumor activity against human EBC1 cells xenografted in CD-1 nude mouse assessed as tumor regression at 15 mg/kg, po qd administered for 5 days on and 2 days off up to 32 days 25006746
SJ-GBM2 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SJ-GBM2 cells 25006746
SK-N-SH qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-SH cells 25006746
RPMI8226 Function assay Inhibition of proteasome subunit beta-1i in human RPMI8226 cells using BODIPY-NC001 by fluorescent densitometry, IC50=0.34μM 25006746
Raji Function assay Inhibition of proteasome subunit beta-1i in human Raji cells using BODIPY- epoxomicin by fluorescent densitometry, IC50=0.46μM 25006746
Raji Function assay Inhibition of proteasome subunit beta-2i in human Raji cells using BODIPY- epoxomicin by fluorescent densitometry, IC50=0.59μM 25006746
RPMI8226 Function assay Inhibition of proteasome subunit beta-2i in human RPMI8226 cells using BODIPY-epoxomicin by fluorescent densitometry, IC50=0.59μM 25006746
Raji Function assay Inhibition of 20s proteasome subunit beta-2c in human Raji cells using BODIPY- epoxomicin by fluorescent densitometry, IC50=1.1μM 25006746
RPMI8226 Function assay Inhibition of 20s proteasome subunit beta-2c in human RPMI8226 cells using BODIPY-epoxomicin by fluorescent densitometry, IC50=1.1μM 25006746
SK-N-MC qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-MC cells 29339252
RD qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for RD cells 29339252
MG 63 (6-TG R) qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for MG 63 (6-TG R) cells 29339252
NCI-H727 Cytotoxicity assay 48 hrs Cytotoxicity against human NCI-H727 cells assessed as reduction in cell viability after 48 hrs by Hoechst 33342 staining based HCS assay, EC50=0.3μM 29339252
PC3 Cytotoxicity assay 48 hrs Cytotoxicity against human PC3 cells assessed as reduction in cell viability after 48 hrs by Hoechst 33342 staining based HCS assay, EC50=0.33μM 29339252
HuH7 Cytotoxicity assay 48 hrs Cytotoxicity against human HuH7 cells assessed as reduction in cell viability after 48 hrs by Hoechst 33342 staining based HCS assay, EC50=0.39μM 29339252
Caco2 Cytotoxicity assay 48 hrs Cytotoxicity against human Caco2 cells assessed as reduction in cell viability after 48 hrs by Hoechst 33342 staining based HCS assay, EC50=1.3μM 29339252
DAOY qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for DAOY cells 30380863
A673 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for A673 cells 30380863
Rh41 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh41 cells 30380863
A20 Function assay Inhibition of LMP2 in mouse A20 cells by ELISA, IC50=0.328μM 30380863
A20 Function assay Inhibition of 20S proteosome beta 5 in mouse A20 cells by ELISA, IC50=0.401μM 30380863
MOLT4 Function assay Inhibition of 20S proteosome beta 5 in human MOLT4 cells by ELISA, IC50=0.422μM 30380863
A20 Function assay Inhibition of MECL1 in mouse A20 cells by ELISA, IC50=0.699μM 30380863
MOLT4 Function assay Inhibition of MECL1 in human MOLT4 cells by ELISA, IC50=0.902μM 30380863
A20 Function assay Inhibition of 20S proteosome beta 2 in mouse A20 cells by ELISA, IC50=0.913μM 30380863
MOLT4 Function assay Inhibition of 20S proteosome beta 2 in human MOLT4 cells by ELISA, IC50=0.927μM 30380863
PBMC Function assay 100 nM 3 to 72 hrs Inhibition of 20S proteasome beta 5i in human PBMC cells assessed as induction of PSMB5 expression at 100 nM after 3 to 72 hrs by RT-PCR analysis 31283222
PBMC Function assay 100 nM 3 to 72 hrs Inhibition of 20S proteasome beta 5i in human PBMC cells assessed as induction of PSMB6 expression at 100 nM after 3 to 72 hrs by RT-PCR analysis 31283222
PBMC Function assay 100 nM 3 to 72 hrs Inhibition of 20S proteasome beta 5i in human PBMC cells assessed as induction of PSMB7 expression at 100 nM after 3 to 72 hrs by RT-PCR method 31283222
Click to View More Cell Line Experimental Data

Biological Activity

Description ONX-0914 (PR-957) is a potent and selective immunoproteasome inhibitor with minimal cross-reactivity for the constitutive proteasome in a cell-free assay.
Features The first highly selective, small molecule inhibitor of the immunoproteasome. Potential use in cancer and autoimmune diseases (e.g. rheumatoid arthritis, inflammatory bowel disease, and lupus).
Targets
LMP7 [1]
(Cell-free assay)
~10 nM
In vitro
In vitro ONX-0914 is 20- to 40-fold more selective for LMP7 over the next most sensitive sites, β5 or LMP2. ONX-0914 blocks presentation of LMP7-specific, MHC-I–restricted antigens in vitro and in vivo with minimal cross-reactivity for the constitutive proteasome. Selective inhibition of LMP7 by ONX-0914 blocks production of interleukin-23 (IL-23) by activated monocytes and interferon-gamma and IL-2 by T cells. LMP7 inhibition blocks production of IL-23 by ~90% and of tumor necrosis factor-α (TNF-α) and IL-6 by ~50%.[1]
In Vivo
In vivo In mouse models of rheumatoid arthritis and lupus, ONX-0914 treatment reverses signs of disease and results in reductions in cellular infiltration, cytokine production and autoantibody levels at well-tolerated doses. The maximum tolerated dose (MTD) of ONX-0914 in mice to be 30 mg/kg body weight. IFN-g release is inhibited by ~60% at LMP7-selective concentrations of ONX-0914 and by ~90% at higher concentrations. Production of IL-2 is also inhibited by ~50%.[1]
Animal Research Animal Models collagen antibody–induced arthritis (CAIA) and collagen-induced arthritis (CIA)
Dosages 2, 6 or 10 mg/kg
Administration i.v.

Chemical Information & Solubility

Molecular Weight 580.67 Formula

C31H40N4O7
CAS No. 960374-59-8 SDF Download ONX-0914 (PR-957) SDF
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
Storage (From the date of receipt)

In vitro
Batch:

DMSO : 100 mg/mL ( (172.21 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Water : 100 mg/mL

Ethanol : 100 mg/mL


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In vivo
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Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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