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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. J Neuroinflammation. 2024 Aug 2;21(1):191.
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). Br J Cancer. 2023 Mar;128(7):1377-1390.
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). Br J Cancer. 2023 Mar;128(7):1377-1390.
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. Oncoimmunology. 2022 Dec 15;12(1):2156091.
DU145 cells 300 nM 24 hours ONX 0914 induced poly-ubiquitin accumulation in DU145 cells and triggered apoptosis via both intrinsic and extrinsic pathways. Oncoimmunology. 2022 Dec 15;12(1):2156091.
Human peripheral blood mononuclear cells (PBMCs) 100 nM 24 hours ONX-0914 reduced the secretion of GM-CSF and IL-23 EMBO Mol Med. 2014 Feb;6(2):226-38.
Mouse splenic CD4+ T cells 300 nM 3 days ONX-0914 inhibited Th17 cell differentiation EMBO Rep. 2018 Dec;19(12):e46512.
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. Adv Sci (Weinh). 2024 Nov;11(44):e2405318.
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. Adv Sci (Weinh). 2024 Nov;11(44):e2405318.
Mouse splenocytes 300 nM Overnight ONX-0914 reduced the surface expression of H-2Kb EMBO Rep. 2018 Dec;19(12):e46512.
Human PBMCs 300 nM Overnight ONX-0914 inhibited IL-6 secretion EMBO Rep. 2018 Dec;19(12):e46512.

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 EMBO Rep. 2018 Dec;19(12):e46512.
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. Br J Cancer. 2023 Mar;128(7):1377-1390.
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. Oncoimmunology. 2022 Dec 15;12(1):2156091.
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 EMBO Mol Med. 2014 Feb;6(2):226-38.
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. Basic Res Cardiol. 2021 Feb 1;116(1):7
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. Arterioscler Thromb Vasc Biol. 2024 Jun;44(6):1346-1364
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. Adv Sci (Weinh). 2024 Nov;11(44):e2405318.

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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