Oprozomib 是一种可口服的选择性肽环氧酮类蛋白酶体抑制剂，诱导多发性骨髓瘤细胞凋亡。它对蛋白酶体 (β5) 和免疫蛋白酶体 (LMP7) 的IC50分别为 36 和 82 nM。

Oprozomib (ONX 0912) , an inhibitor for CT-L activity of 20S proteasome β5（IC50=36 nM）/LMP7（IC50=82 nM）, is orally bioavailable. Oprozomib also has potential antineoplastic activity.

在多种人类肿瘤移植瘤和小鼠同系模型中,Oprozomib能够抑制>80％蛋白酶,诱导抗肿瘤反应.Oprozomib经过重复口服后,在动物的大多数组织具有良好的安全性与耐受性.

Oprozomib具有抗MM活性,可以抑制MM细胞的迁移和血管生成。Oprozomib也能抑制caspase-8,caspase-9,caspase-3和PARP的激活。

ELISA-based active site binding assay: Samples (lysed cells or tissue homogenates) are treated for 1 h at room temperature with the biotinylated active site probe PR-584 (5-15 μM). Samples are denatured by addition of SDS (0.9% final) and heating to 100 °C for 5 min. The denatured samples are transferred to a 96-well or 384-well filter plat, mixed with streptavidin-sepharose beads (2.5-5 μL packed beads/well), and incubated for 1 h at room temperature on a plate shaker. The beads are washed 5 times with 100-200 μL /well of ELISA buffer (PBS, 1% bovine serum albumin, 0.1% Tween-20) by vacuum filtration. The beads are incubated overnight at 4 °C on a plate shaker with the following antibodies recognizing the six catalytic subunits diluted into ELISA buffer: β5, β1, and β2 diluted 1:3000, LMP7 and LMP2 diluted 1:5000, and MECL-1 diluted 1:1000. The beads are washed 5 times with 100-200 μL /well of ELISA buffer and incubated with HRP-conjugated secondary antibody diluted 1:5000 in ELISA buffer and incubated 2 h at room temperature on a plate shaker. The beads are washed 5 times with 100-200 μL /well of ELISA buffer and developed for chemiluminsecence signal using the supersignal ELISA pico substrate following the manufacturer's instructions. Luminescence is measured on a plate reader and converted to ng of proteasome or μg/ml of lysate by comparison with 20S proteasome or untreated cell lysate standard curves. For proteasome inhibitor studies, active site probe binding values are expressed as the percent of binding relative to DMSO treated cells.

MTT assay(Only for Reference)

935888-69-0

C25H32N4O7S

532.61

PR-047;奥泼佐米;ONX 0912

H2O:<1 mgml
DMSO:93 mg/mL (174.6 mM)
Ethanol:<1 mgml
Powder: -20°C for 3 years
In solvent: -80°C for 2 years