CA-074 methyl ester (CA-074 Me)

製品コードS7420 バッチS742001

印刷

化学情報

Chemical Structure Synonyms Cathepsin B Inhibitor IV Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C19H31N3O6
分子量 397.47 CAS No. 147859-80-1
Solubility (25°C)* 体外 DMSO 79 mg/mL (198.75 mM)
Ethanol 79 mg/mL (198.75 mM)
Water 2.5 mg/mL (6.28 mM)
体内 （毎回新しく調製した物を用意してください）
Clear solution
5% DMSO 95% Corn oil
2.5mg/ml Taking the 1 mL working solution as an example, add 50 μL of 50 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results. 
Clear solution
5%DMSO 40%PEG300 5%Tween80 50%ddH2O
5.0mg/ml Taking the 1 mL working solution as an example, add 50 μL of 100 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results. 
* <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 CA-074 methyl ester (CA-074 Me, Cathepsin B Inhibitor IV) is a membrane-permeable derivative of CA-074 and acts as an irreversible cathepsin B inhibitor.
in vitro CA-074Me is able to inhibit cathepsin L within living HL-60 cells and bloodstream forms of Trypanosoma brucei brucei, but does not inhibit cathepsin L in the absence of thiols. CA-074Me is converted into CA-074 by intracellular esterasesand is, therefore, able to inhibit cathepsin B in GSH-depleted HL-60 cell. It is suggested that CA-074 rather than CA-074Me should be used to selectively inhibit cathespsin B within living cells[1]. Myotube size and number and induced levels of fusion-related creatine phosphokinase activity and myosin heavy-chain protein are reduced from 30 to 50% in CA074Me-treated myoblasts. These reductions are also dose related. Micromolar concentrations of CA074Me inhibit catB activity in differentiating myoblasts[2].
in vivo Administration of CA074Me to the London APP mice results in significant improvement in memory deficit, reduces amyloid plaque load in brain, reduces levels of Aβ40 and Aβ42 in brain, and reduces C-terminal β-secretase fragment (CTFβ) derived from APP by β-secretase when compared with untreated control animals. It has no effect on any of these parameters in mice expressing the Swe mutant β-secretase site of APP (in Swedish/London APP mice). In vivo icv administration of CA074Me to normal guinea pigs results in substantial reduction of brain Aβ levels and inhibits β-secretase activity[3].

プロトコル(参考用のみ)

細胞アッセイ 細胞株 HL-60 cells
濃度 100 μM
反応時間 2 h
実験の流れ HL-60 cells are pre-treated for 24 h with 200 μM BSO followed by 60 min with 1 mM DEM. Thereafter, the cells(1×106/ml) are incubated with 100 μM CA-074 or CA-074Me, in the presence of 1% DMSO, 200 μM BSO and 1 mM DEM at 37°C. Control cultures are treated with 1% DMSO alone or with 100 μM Z-FA-DMK in the presence of 200 μM BSO and 1 mM DEM. Untreated HL-60 cells are incubated with 100 μM CA-074 or CA-074Me, in the presence of 1% DMSO at 37°C. Untreated control cultures are incubated with 1% DMSO alone or with 100 μM Z-FA-DMK. After 2 h incubation, cells are washed three times with PBS/1% glucose and lysed in 100 mM citrate, pH 5.0, 2% Chaps (106 cells/100 μl). Subsequently, the lysate is centrifuged and the clarified supernatant used to assay for proteolytic activity.
動物実験 動物モデル London APP mice
投薬量 1 mg/ml
投与方法 An ALZET osmotic minipump was implanted subcutaneously in the midscapular area of the back of each animal. A catheter was connected to the osmotic minipump and inserted into the lateral ventricle of the brain (icv).

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：

Melatonin alleviates chronic stress-induced hippocampal microglia pyroptosis and subsequent depression-like behaviors by inhibiting Cathepsin B/NLRP3 signaling pathway in rats [ Transl Psychiatry, 2024, 14(1):166] PubMed: 38538614
Gasdermin D regulates soluble fms-like tyrosine kinase 1 release in macrophages [ Reprod Biol, 2024, 24(1):100857] PubMed: 38295720
Monocyte-derived macrophages orchestrate multiple cell-type interactions to repair necrotic liver lesions in disease models [ J Clin Invest, 2023, 133(15)e166954] PubMed: 37338984
The impact of cycling hypoxia on the phenotype of HPV-positive cervical cancer cells [ J Med Virol, 2023, 95(12):e29280] PubMed: 38054507
Resistance of hypervirulent Klebsiella pneumoniae to cathepsin B-mediated pyroptosis in murine macrophages [ Front Immunol, 2023, 14:1207121] PubMed: 37457695
Parallel use of human stem cell lung and heart models provide insights for SARS-CoV-2 treatment [ Stem Cell Reports, 2023, 18(6):1308-1324] PubMed: 37315523
Acid Ceramidase Inhibitor LCL-805 Antagonizes Akt Signaling and Promotes Iron-Dependent Cell Death in Acute Myeloid Leukemia [ Cancers (Basel), 2023, 15(24)5866] PubMed: 38136410
Effects of HMGB1/RAGE/cathespin B inhibitors on alleviating hippocampal injury by regulating microglial pyroptosis and caspase activation in neonatal hypoxic-ischemic brain damage [ J Neurochem, 2023, 167(3):410-426] PubMed: 37753942
Trimethylamine N-Oxide (TMAO) Inducing Endothelial Injury: UPLC-MS/MS-Based Quantification and the Activation of Cathepsin B-Mediated NLRP3 Inflammasome [ Molecules, 2023, 28(9)3817] PubMed: 37175227
Pyroptosis leads to loss of centrosomal integrity in macrophages [ bioRxiv, 2023, 10.1101/2023.11.22.568260] PubMed: none

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。