Oprozomib

製品コードS7049 バッチS704901

印刷

化学情報

Chemical Structure Synonyms ONX 0912, PR-047 Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C25H32N4O7S
分子量 532.61 CAS No. 935888-69-0
Solubility (25°C)* 体外 DMSO 107 mg/mL (200.89 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.

溶剤液（一定の濃度）を調合する

生物活性

製品説明 Oprozomibが選択的に 20Sプロテアソーム β5/LMP7 のCT-Lの活性を阻害し、IC50 が 36 nM/82 nMです。
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].

プロトコル(参考用のみ)

キナーゼアッセイ 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.
細胞アッセイ 細胞株 MM.1S, MM.1R, RPMI-8226, KMS12, INA-6, OPM-2, Dox-40
濃度 ~1 μM
反応時間 48 h
実験の流れ MTT assay
動物実験 動物モデル Non-Hodgkin’s lymphoma cell line RL xenograft, colorectal tumor cell line CT-26 xenograft
投薬量 30 mg/kg, twice weekly on days 1 and 2
投与方法 p.o.

カスタマーフィードバック

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

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

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

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

各々の製品のための特定の保管と取扱い情報は、製品データシートの上で示されます。大部分のSelleck製品は、推薦された状況の下で安定です。製品は、推薦された保管温度と異なる温度で、時々出荷されます。長期の保管のために必要とされてそれと異なる温度で、多くの製品は、短期もので安定です。品質を維持するが、夜通しの積荷のために最も経済的な貯蔵状況を用いてあなたの送料を保存する状況の下に、製品が出荷されることを、我々は確実とします。製品の受領と同時に、製品データシートの上で貯蔵推薦に従ってください。