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DRUG:

ONX 0914

i
Other names: ONX 0914, PR 957, PR-957
Company:
Amgen, Protalex
Drug class:
Immunoproteasome inhibitor
Related drugs:
4ms
Enhancing the immunogenicity of Wilms tumor 1 epitope in mesothelioma cells with immunoproteasome inhibitors. (PubMed, PLoS One)
These results suggest that ONX-0914 prevents the internal destructive cleavage of WT1235 by IP, thereby promoting the specific presentation of the WT1 epitope by MESO-4. In conclusion, selective IP inhibitors might offer a means to modulate cancer cell immunogenicity by directing the presentation of particular tumor epitopes.
Journal
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CD8 (cluster of differentiation 8) • WT1 (WT1 Transcription Factor)
|
ONX 0914
over1year
Gastric cancer cell types display distinct proteasome/immunoproteasome patterns associated with migration and resistance to proteasome inhibitors. (PubMed, J Cancer Res Clin Oncol)
These results suggest that pharmacological inhibition of the immunoproteasome may be useful in treating metastatic gastric cancers.
Journal
|
ONX 0914
over1year
Immunoproteasome inhibition prevents progression of castration-resistant prostate cancer. (PubMed, Br J Cancer)
We define a critical role of the immunoproteasome in CRPC and propose immunoproteasome inhibition as a promising therapeutic approach to suppress CRPC progression.
Journal • IO biomarker
|
IFNG (Interferon, gamma) • IL17A (Interleukin 17A) • PSMB8 (Proteasome 20S Subunit Beta 8)
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ONX 0914
over1year
Immunogenic cell death triggered by impaired deubiquitination in multiple myeloma relies on dysregulated type I interferon signaling. (PubMed, Front Immunol)
In this paper, we applied the protein homeostasis disruptors bortezomib (BTZ), ONX0914, RA190 and PR619 to various MM cell lines and primary patient samples to investigate their ability to induce immunogenic cell death (ICD). The immunological relevance of blocking de-ubiquitination in MM was further reflected by the ability of PR619-induced apoptotic cells to facilitate dendritic cell (DC) maturation via type I IFN-dependent mechanisms. Altogether, our findings identify de-ubiquitination inhibition as a promising strategy for inducing ICD of MM to expand current available treatments.
Journal
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ERN1 (Endoplasmic Reticulum To Nucleus Signaling 1)
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bortezomib • ONX 0914
almost2years
Suppression of prostate cancer and amelioration of the immunosuppressive tumor microenvironment through selective immunoproteasome inhibition. (PubMed, Oncoimmunology)
The anti-tumor effect of immunoproteasome inhibitor ONX 0914 was tested in mouse and human PC cells and the in vivo therapeutic efficacy of immunoproteasome inhibition was analyzed in transgenic adenocarcinoma of the mouse prostate (TRAMP) mice in preventive and therapeutic settings and in castration-resistant (CR)PC after castration...Thus, immunoproteasome inhibition shows remarkable efficacy against PC progression in vivo and impedes tumor recurrence in CRPC-TRAMP mice by blocking the immunosuppressive inflammatory response in the tumor microenvironment. In conclusion, we show that the immunoproteasome is a promising drug target for the treatment of PC.
Journal
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IL6 (Interleukin 6) • IL17A (Interleukin 17A) • IL23A (Interleukin 23 Subunit Alpha) • PSMB8 (Proteasome 20S Subunit Beta 8)
|
ONX 0914
almost2years
ONX-0914 Induces Apoptosis and Autophagy with p53 Regulation in Human Glioblastoma Cells. (PubMed, Cancers (Basel))
In an orthotopic mouse model, TMZ plus ONX-0914 reduced tumor progression better than the control or TMZ alone. These data suggest that ONX-0914 is a novel therapeutic drug for glioblastoma.
Journal • PARP Biomarker • IO biomarker
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BCL2 (B-cell CLL/lymphoma 2) • PSMB8 (Proteasome 20S Subunit Beta 8)
|
BCL2 expression
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ONX 0914
2years
Inhibition of p38 MAPK or immunoproteasome overcomes resistance of chronic lymphocytic leukemia cells to Bcl-2 antagonist venetoclax. (PubMed, Cell Death Dis)
Inhibition of immunoproteasome with ONX-0914 suppressed activity of immunoproteasome and synergized with venetoclax against primary CLL cells. Inhibition of p38 MAPK or immunoproteasome triggered apoptosis in CLL cells and overcame the resistance to venetoclax of MEC-1 VER cells and venetoclax-insensitive primary CLL cells. In conclusion, the p38 MAPK pathway and immunoproteasome represent novel targets to combat venetoclax resistance in CLL.
Journal
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BCL2 (B-cell CLL/lymphoma 2) • CD19 (CD19 Molecule) • MCL1 (Myeloid cell leukemia 1) • IFNG (Interferon, gamma) • CD40LG (CD40 ligand)
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CD19 positive • MCL1 expression • MCL1 underexpression • BAX expression • BAX underexpression
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Venclexta (venetoclax) • ONX 0914
3years
Inhibition of the Immunoproteasome Subunit LMP7 Ameliorates Cerebral White Matter Demyelination Possibly via TGFβ/Smad Signaling. (PubMed, Evid Based Complement Alternat Med)
Surprisingly, PR957 alone had no effects on the neuroinflammation response and the activation of TGFβ/Smad signaling in the sham-operated (BCAS-nonoperated) mice. The possible mechanism underlying this was attributed to that the immunoproteasome regulates TGFβ/Smad signaling-mediated neuroinflammation and oligodendrocyte remyelination.
Journal
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TNFA (Tumor Necrosis Factor-Alpha) • IGF1 (Insulin-like growth factor 1) • IL10 (Interleukin 10) • IL1B (Interleukin 1, beta)
|
ONX 0914
4years
Expression of the immunoproteasome subunit β5i in non-small cell lung carcinomas. (PubMed, J Clin Pathol)
The expression of immunoproteasome can be explored as both a prognostic factor and a potential therapeutic target in NSCLCs. Since immunoproteasomes have crucial role in the antigen presentation, further studies may help to provide essential knowledge for therapeutic strategies in anticancer immunotherapy.
Journal
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CD8 (cluster of differentiation 8)
|
MG132 • ONX 0914
over4years
Proteasome inhibitors diminish c-Met expression and induce cell death in non-small cell lung cancer cells. (PubMed, Oncol Res)
Three proteasome inhibitors,Bortezomib, MG132, and ONX 0914, were used in this study. ONX 0914 did not alter cell viability in either H441, however, it did induce celldeath among H460, A549, and H1299 cells. This study reveals that different proteasomeinhibitors produce varied inhibitory effects in NSCLS cell lines.
Journal
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MET (MET proto-oncogene, receptor tyrosine kinase) • HGF (Hepatocyte growth factor)
|
MET expression
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bortezomib • ONX 0914
over4years
The impact of regional astrocyte interferon-γ signaling during chronic autoimmunity: a novel role for the immunoproteasome. (PubMed, J Neuroinflammation)
Taken together, our data reveal a protective role for IFNγ in chronic neuroinflammation and identify a novel function of the iP in astrocytes during CNS autoimmunity.
Journal
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IFNG (Interferon, gamma)
|
IFNG expression
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ONX 0914