Home Proteases Proteasome inhibitor Oprozomib For research use only.

Oprozomib

Synonyms: ONX 0912, PR-047

Oprozomib is an orally bioavailable inhibitor for CT-L activity of 20S proteasome β5/LMP7 with IC50 of 36 nM/82 nM. Phase 1/2.

Oprozomib Chemical Structure

Oprozomib Chemical Structure

CAS: 935888-69-0

Selleck's Oprozomib has been cited by 20 Publications

1 Customer Review

Purity & Quality Control

Batch: Purity: 99.97%
99.97

Oprozomib Related Products

Signaling Pathway

Proteasome Signaling Pathways

Proteasome Signaling Pathway

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Biological Activity

Description Oprozomib is an orally bioavailable inhibitor for CT-L activity of 20S proteasome β5/LMP7 with IC50 of 36 nM/82 nM. Phase 1/2.
Targets
20S proteasome β5 [1] 20S proteasome LMP7 [1]
36 nM 82 nM
In vitro
In vitro The anti-MM activity of Oprozomib is associated with activation of caspase-8, caspase-9, caspase-3, and PARP, as well as inhibition of migration of MM cells and angiogenesis. [2]
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.
Cell Research Cell lines MM.1S, MM.1R, RPMI-8226, KMS12, INA-6, OPM-2, Dox-40
Concentrations ~1 μM
Incubation Time 48 h
Method MTT assay
Experimental Result Images Methods Biomarkers Images PMID
Western blot Cyclin D1 / Cyclin D2 / Cyclin E / p21(waf1/cip1) / p27(kip1) β-catenin / GRP94 / PERK / p-EIF2α / BiP / PDI / ATF4 Bcl-2 / Bcl-xL / Mcl-1 / Bik / Bim / Bax / Bak 20110419
Growth inhibition assay Cell viability 20805366
In Vivo
In vivo Oprozomib is demonstrated an absolute bioavailability of up to 39% in rodents and dogs. It is well tolerated with repeated oral administration at doses resulting in >80% proteasome inhibition in most tissues and elicited an antitumor response in multiple human tumor xenograft and mouse syngeneic models [1].
Animal Research Animal Models Non-Hodgkin’s lymphoma cell line RL xenograft, colorectal tumor cell line CT-26 xenograft
Dosages 30 mg/kg, twice weekly on days 1 and 2
Administration p.o.
NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT01999335 Terminated
Multiple Myeloma
Amgen
 July 30 2014 Phase 1
NCT01832727 Terminated
Multiple Myeloma
Amgen
 July 2 2013 Phase 1|Phase 2
NCT01416428 Terminated
Multiple Myeloma|Waldenstrom Macroglobulinemia
Amgen
 October 15 2011 Phase 1|Phase 2

Chemical Information & Solubility

Molecular Weight 532.61 Formula

C25H32N4O7S
CAS No. 935888-69-0 SDF --
Smiles CC1=NC=C(S1)C(=O)NC(COC)C(=O)NC(COC)C(=O)NC(CC2=CC=CC=C2)C(=O)C3(CO3)C
Storage (From the date of receipt)

In vitro
Batch:

DMSO : 100 mg/mL ( (187.75 mM)； Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Water : Insoluble

Ethanol : Insoluble


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In vivo
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Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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