| Name | Oprozomib |
| Description | Oprozomib (PR-047) (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. |
| Cell Research | MTT assay(Only for Reference) |
| Kinase Assay | 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. |
| In vitro | In various human tumor xenografts and mouse syngeneic models, Oprozomib can inhibit over 80% of proteasomes, inducing an anti-tumor response. Following repeated oral administration, Oprozomib demonstrates good safety and tolerability across most tissues in animals. |
| In vivo | Oprozomib exhibits anti-MM (multiple myeloma) activity by inhibiting the migration and angiogenesis of MM cells. Furthermore, Oprozomib suppresses the activation of caspase-8, caspase-9, caspase-3, and PARP. |
| Storage | store at low temperature | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice. |
| Solubility Information | H2O : < 1 mg/mL (insoluble or slightly soluble)
DMSO : 93 mg/mL (174.6 mM)
Ethanol : < 1 mg/mL (insoluble or slightly soluble)
|
| Keywords | apoptosis | inhibit | bioavailable | immunoproteasome LMP7 | PR047 | PR 047 | Proteasome | Autophagy | orally | ONX0912 | ONX-0912 | Inhibitor | epoxyketone | Oprozomib |
| Inhibitors Related | Stavudine | Sodium 4-phenylbutyrate | Hydroxychloroquine | Guanidine hydrochloride | Taurine | Curcumin | Oxyresveratrol | Paeonol | Naringin | Gefitinib |
| Related Compound Libraries | Bioactive Compound Library | Anti-Cancer Clinical Compound Library | Drug Repurposing Compound Library | Inhibitor Library | Anti-Aging Compound Library | Bioactive Compounds Library Max | Anti-Cancer Compound Library | Anti-Liver Cancer Compound Library | Anti-Cancer Active Compound Library | Anti-Cancer Drug Library |
United States
