Oprozomib (ONX 0912)

Catalog No.S7049 Synonyms: PR-047

For research use only.

Oprozomib (ONX 0912, PR-047) 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 (ONX 0912) Chemical Structure

CAS No. 935888-69-0

Selleck's Oprozomib (ONX 0912) has been cited by 18 publications

Purity & Quality Control

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Biological Activity

Description Oprozomib (ONX 0912, PR-047) 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

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]

Assay
Methods Test Index PMID
Growth inhibition assay Cell viability 20805366
Western blot Bcl-2 / Bcl-xL / Mcl-1 / Bik / Bim / Bax / Bak ; β-catenin / GRP94 / PERK / p-EIF2α / BiP / PDI / ATF4 ; Cyclin D1 / Cyclin D2 / Cyclin E / p21(waf1/cip1) / p27(kip1) 22929803 20110419
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].

Protocol (from reference)

Kinase Assay:[3]
  • 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:[2]
  • 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
  • (Only for Reference)
Animal Research:[1]
  • 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.
  • (Only for Reference)

Solubility (25°C)

In vitro

DMSO 100 mg/mL
(187.75 mM)
Water Insoluble
Ethanol Insoluble

* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Chemical Information

Molecular Weight 532.61
Formula

C25H32N4O7S

CAS No. 935888-69-0
Storage 3 years -20°C powder
2 years -80°C in solvent
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

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Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
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Molarity Calculator

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Clinical Trial Information

NCT Number Recruitment Interventions Conditions Sponsor/Collaborators Start Date Phases
NCT01999335 Terminated Drug: Oprozomib|Drug: Pomalidomide|Drug: Dexamethasone Multiple Myeloma Amgen July 30 2014 Phase 1
NCT01832727 Terminated Drug: Oprozomib|Drug: Dexamethasone Multiple Myeloma Amgen July 2 2013 Phase 1|Phase 2
NCT01416428 Terminated Drug: oprozomib Multiple Myeloma|Waldenstrom Macroglobulinemia Amgen October 15 2011 Phase 1|Phase 2

(data from https://clinicaltrials.gov, updated on 2022-01-17)

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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