MLN-4760

製品コードS8940 バッチS894001

印刷

化学情報

Chemical Structure Synonyms N/A Storage
(From the date of receipt)		 3 years -20°C powder
化学式
C19H23Cl2N3O4
分子量 428.31 CAS No. 305335-31-3
Solubility (25°C)* 体外 Water 86 mg/mL (200.78 mM)
Ethanol 10 mg/mL (23.34 mM)
DMSO Insoluble
体内 （毎回新しく調製した物を用意してください）
Clear solution
5%ethyl alcohol 40%PEG300 5%Tween80 50%ddH2O

この製剤はselleckのラボで検証済みです。上記の溶解方法がご要望を満たさない場合、selleckの営業担当までお問い合わせ頂ければ、個別の試験を行います。

 0.500mg/ml (1.17mM) Taking the 1 mL working solution as an example, add 50 μL of 10 mg/ml clarified ethyl alcohol 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. 
Clear solution
5% ethyl alcohol 95% Corn oil

この製剤はselleckのラボで検証済みです。上記の溶解方法がご要望を満たさない場合、selleckの営業担当までお問い合わせ頂ければ、個別の試験を行います。

 0.500mg/ml (1.17mM) Taking the 1 mL working solution as an example, add 50 μL of 10 mg/ml clear ethyl alcohol stock solution to 950 μL of corn oil and mix evenly. 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 MLN-4760 (compound 16) is a potent and selective inhibitor of human angiotensin-converting enzyme 2 (ACE2) with IC50 of 0.44 nM. MLN-4760 also inhibits bovine carboxypeptidase A (CPDA) with IC50 of 27 μM.
in vitro

In vitro, conversion from angiotensin II to angiotensin-(1–7) by mouse ACE2 is blocked by MLN-4760 (10 μM). This compound inhibits both human and mouse ACE2 activity.[3] In huMNCs, this chemical-B (an isomer of MLN-4760) detects 63% ACE2 with 28-fold selectivity over ACE. In huCD34+ cells, this compound-B detects 38% of ACE2 activity with 63-fold selectivity. In mu-heart and muMNCs, this chemical-B is 100- and 228-fold selective for ACE2, respectively. In muLin- cells, this compound-B detects 25% ACE2 activity with a pIC50 of 6.3. The racemic mixture and this chemical-A shows lower efficacy and poor selectivity for ACE2 in MNCs and mu-heart.[4]
in vivo

MLN-4760 blocks ACE2 activity, thus significantly reverses the elevation of carotid Ang-(1-7) level and the decline of carotid Ang II level induced by NaHS in mice. The anti-atherosclerotic property of NaHS is also significantly abolished by treatment with this compound.[2]

プロトコル(参考用のみ)

細胞アッセイ 細胞株 mononuclear cells (MNCs), huCD34+ cells, mu-lineage-depleted (muLin-) cells
濃度 0.01 nM to 300 μM
反応時間 1 h, 4 h
実験の流れ

In the case of cell lysates, 10 μg of total protein is assayed for activity in a buffer with the following composition: 50mM MES (4-morpholineethanesulphonic acid), 300mM NaCl, 10μM ZnCl2 and 0.01% Triton X-100, pH 6.5. Reaction is initiated by the addition of 5×10-5 M substrate. Where applicable, recombinant enzymes are used at a concentration of 0.01 μg per reaction. The fluorescence measurements are performed in the black microtiter plates in a total volume of 100 μl. The plates are read using a fluorescence plate reader SpectraMax M5 at an excitation wavelength 320 nm and emission wavelength 405 nm Fluorescence resulting from the substrate hydrolysis increased with time, and achieved maximum by 1 h with recombinant enzyme however with cell/tissue lysates the maximum fluorescence is observed by 4 h of incubation. Therefore fluorescence recorded at 1 and 4 h of reaction time is taken for calculation of percent enzyme inhibition, when using recombinant enzymes and cell/tissue lysates, respectively. ACE2 activity is defined as the ACE2 inhibitor-sensitive fluorescence and ACE activity is defined as the ACE inhibitor, captopril-sensitive fluorescence, and are expressed as percent inhibition. Unless specified, this compound is used in concentration ranging from 0.01 nM to 300 μM.
動物実験 動物モデル C57BL/6J male apoE−/− mice
投薬量 0.5 mg/kg
投与方法 IP

参考

  • https://pubmed.ncbi.nlm.nih.gov/12358520/
  • https://pubmed.ncbi.nlm.nih.gov/29066981/
  • https://pubmed.ncbi.nlm.nih.gov/22777933/
  • https://pubmed.ncbi.nlm.nih.gov/26851370/

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：

ACE2 negatively regulates the Warburg effect and suppresses hepatocellular carcinoma progression via reducing ROS-HIF1α activity [ Int J Biol Sci, 2023, 19(8):2613-2629] PubMed: 37215979

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。