960374-59-8

960374-59-8 structure

Name: ONX-0914 (PR-957)
Chemical Name: (2S)-3-(4-methoxyphenyl)-N-[(2S)-1-(2-methyloxiran-2-yl)-1-oxo-3-phenylpropan-2-yl]-2-[[(2S)-2-[(2-morpholin-4-ylacetyl)amino]propanoyl]amino]propanamide
CAS Number: 960374-59-8
Molecular Formula: C₃₁H₄₀N₄O₇
Molecular Weight: 580.672
Catalog: Biochemical Inhibitor Proteases Proteasome inhibitor
Create Date: 2016-09-14 18:29:07
Modify Date: 2024-01-02 00:17:52
ONX-0914 (PR-957) is a potent and selective immunoproteasome inhibitor with minimal cross-reactivity for the constitutive proteasome.IC50 Value: ~10 nM [1]in vitro: PR-957 blocked presentation of LMP7-specific, MHC-I-restricted antigens in vitro and in vivo. Selective inhibition of LMP7 by PR-957 blocked production of interleukin-23 (IL-23) by activated monocytes and interferon-gamma and IL-2 by T cells [1].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].

Name	(2S)-3-(4-methoxyphenyl)-N-[(2S)-1-(2-methyloxiran-2-yl)-1-oxo-3-phenylpropan-2-yl]-2-[[(2S)-2-[(2-morpholin-4-ylacetyl)amino]propanoyl]amino]propanamide
Synonyms	qc-7242 D-erythro-3-Pentulose, 4,5-anhydro-1,2-dideoxy-4-C-methyl-2-[[N-[2-(4-morpholinyl)acetyl]-L-alanyl-O-methyl-L-tyrosyl]amino]-1-phenyl- 4,5-Anhydro-1,2-dideoxy-4-methyl-2-{[N-(4-morpholinylacetyl)-L-alanyl-O-methyl-L-tyrosyl]amino}-1-phenyl-D-erythro-pent-3-ulose ONX-0914 ONX0914

Description	ONX-0914 (PR-957) is a potent and selective immunoproteasome inhibitor with minimal cross-reactivity for the constitutive proteasome.IC50 Value: ~10 nM [1]in vitro: PR-957 blocked presentation of LMP7-specific, MHC-I-restricted antigens in vitro and in vivo. Selective inhibition of LMP7 by PR-957 blocked production of interleukin-23 (IL-23) by activated monocytes and interferon-gamma and IL-2 by T cells [1].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].
Related Catalog	Signaling Pathways >> Metabolic Enzyme/Protease >> Proteasome Research Areas >> Inflammation/Immunology
References	[1]. Muchamuel T, et al. A selective inhibitor of the immunoproteasome subunit LMP7 blocks cytokine production and attenuates progression of experimental arthritis. Nat Med. 2009 Jul;15(7):781-7.