Cat. No. Name Size Price Add Cart
KI2120ONX-09145 mg$236
ONX-091410 mg$380

Chemical Characteristic

Product NameONX-0914
SynonymsN/A
CAS No.960374-59-8
Molecular Weight 580.67
FormulaC31H40N4O7
Chemical Namen-(2-(4-morpholinyl)acetyl)-l-alanyl-o-methyl-n-((1s)-2-((2r)-2-methyl-2-oxiranyl)-2-oxo-1-(phenylmethyl)ethyl)-l-tyrosinamide
SmilesC(=O)(C(NC(=O)[C@@H](NC(=O)CN1CCOCC1)C)Cc1ccc(OC)cc1)NC(C(=O)[C@@]1(OC1)C)Cc1ccccc1
Chemical Structure

Biological activities

ONX-0914 is a potent and selective immunoproteasome inhibitor. ONX-0914 has minimal cross-reactivity for the constitutive proteasome. ONX-0914 inhibits low-molecular mass polypeptide-7 (LMP7), the chymotrypsin-like subunit of the immunoproteasome, with an IC50 of ˜10 nM. In vitro, ONX-0914 blocks production of IL-23 by activated monocytes and IFN-γ and IL-2 by T cells. In mouse models of rheumatoid arthritis, ONX-0914 treatment reverses signs of disease and reduces cellular infiltration, cytokine production and autoantibody levels.[1] In vivo in mice, ONX-0914 administration strongly reduced pathological symptoms of dextran sulfate sodium-induced colitis through the blockage of LMP7.[2]

Protocols

In vitro: ONX-0914 is dissolved in DMSO.[3]

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, 15(7): 781-787.
[2] Basler M, et al. Prevention of experimental colitis by a selective inhibitor of the immunoproteasome. J Immunol. 2010, 185(1): 634-641.
[3] de Wilt LH, et al. Proteasome-based mechanisms of intrinsic and acquired bortezomib resistance in non-small cell lung cancer. Biochem Pharmacol. 2012, 83(2): 207-217.

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