Brief 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].
References on ONX-0914:
[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.

Solubility

in DMSO > 10 mM

Melting point

Boiling point

Density

Formula Weight:

Flash point

Storage conditions

Store at -20°C 2 years

Appearance:

White to off-white solid