ONX0914 是选择性的低分子量多肽-7(LMP7)的抑制剂，LMP7 是免疫蛋白酶体的类糜蛋白酶亚单位。它是分枝杆菌蛋白酶体的非竞争性不可逆抑制剂，Ki值为5.2 μM。它通过 HSF-1 介导的 p-TEFb 活化激活潜伏的 HIV-1。

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

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.

In mouse models of rheumatoid arthritis and lupus, the maximum tolerated dose (MTD) of ONX-0914 in mice to be 30 mg/kg body weight.

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.

960374-59-8

C31H40N4O7

580.682

PR-957;ONX 0914;ONX0914

DMSO:35 mg/mL
Powder: -20°C for 3 years
In solvent: -80°C for 2 years