ONX-0914 (PR-957) is an effective and specific immunoproteasome inhibitor, which has minimal cross-reactivity for the constitutive proteasome.

Immunoproteasome:~10 nM

PR-957通过选择性抑制LMP7, 阻断了活化单核细胞产生的白细胞介素-23（IL-23）以及T细胞产生的干扰素-γ和IL-2的生成。

在类风湿性关节炎和红斑狼疮的小鼠模型中，ONX-0914的最大耐受剂量(MTD)为每千克体重30 mg/kg。

20 ng of purified human DDK is pre-incubated with increasing concentrations of each DDK inhibitor for 5 min. Then 10 μCi (γ)-32P ATP and 1.5 μM cold ATP are added in a buffer containing 50 mM Tris-HCl (pH 7.5), 10 mM MgCl2, and 1 mM DTT and incubated for 30 min at 30°C. The proteins are denatured in 1X Laemmli buffer at 100°C followed by SDS-PAGE and autoradiography on HyBlot CL film. Auto-phosphorylation of DDK is used as an indicator of its kinase activity. 32P-labeled bands are quantified using ImageJ and the IC50 values are calculated using GraphPad.