Oprozomib

Catalog No.S7049 Batch:S704902

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Technical Data

Formula

C25H32N4O7S
Molecular Weight 532.61 CAS No. 935888-69-0
Solubility (25°C)* In vitro DMSO 100 mg/mL (187.75 mM)
Water Insoluble
Ethanol Insoluble
* <1 mg/ml means slightly soluble or 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.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

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 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]
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 Assay:[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
Animal Study:[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.

Customer Product Validation

Data from [Data independently produced by , , Archives of Biochemistry and Biophysics, 2018, 639:52-58]

Selleck's Oprozomib has been cited by 21 publications

Dual inhibition of HSF1 and DYRK2 impedes cancer progression [ Biosci Rep, 2023, 43(1)BSR20222102] PubMed: 36622366
Proteasome inhibition as a therapeutic target for the fungal pathogen Cryptococcus neoformans [ Microbiol Spectr, 2023, 11(5):e0190423] PubMed: 37750732
Proteasome inhibition as a therapeutic target for the fungal pathogen Cryptococcus neoformans [ Microbiol Spectr, 2023, 10.1128/spectrum.01904-23] PubMed: 37750732
Mechanism of action of hepatitis B virus S antigen transport-inhibiting oligonucleotide polymer, STOPS, molecules [ Mol Ther Nucleic Acids, 2022, 27:335-348] PubMed: 35024245
Oral Proteasomal Inhibitors Ixazomib, Oprozomib, and Delanzomib Upregulate the Function of Organic Anion Transporter 3 (OAT3): Implications in OAT3-Mediated Drug-Drug Interactions [ Pharmaceutics, 2021, 13(3)314] PubMed: 33670955
Crosstalk between HSPA5 arginylation and sequential ubiquitination leads to AKT degradation through autophagy flux. [ Autophagy, 2020, 10.1080/15548627.2020.1740529] PubMed: 32164484
A Patient-Derived Cell Atlas Informs Precision Targeting of Glioblastoma [ Cell Rep, 2020, 32(2):107897] PubMed: 32668248
Proteasome inhibitors and Smac mimetics cooperate to induce cell death in Diffuse Large B-cell Lymphoma by stabilizing NOXA and triggering mitochondrial apoptosis. [ Int J Cancer, 2020, 10.1002/ijc.32976] PubMed: 32170726
Prolonged unfolded protein reaction is involved in the induction of chronic myeloid leukemia cell death upon oprozomib treatment [ Cancer Sci, 2020, 112(1):133-143] PubMed: 33067904
Charge transfer reaction mechanisms of epoxyketone and boronated peptides at glassy carbon and boron doped diamond electrodes [ J Electroanal Chem (Lausanne), 2020, 878:114733] PubMed: 33020701

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

NOT FOR HUMAN, VETERINARY DIAGNOSTIC OR THERAPEUTIC USE.