受注:045-509-1970 |
技術サポート:[email protected] 平日9:00〜18:00 1営業日以内にご連絡を差し上げます |
Synonyms | BML-275,Compound C | Storage (From the date of receipt) |
3 years -20°C powder 1 years -80°C in solvent |
|
化学式 | C24H25N5O |
|||
分子量 | 399.49 | CAS No. | 866405-64-3 | |
Solubility (25°C)* | 体外 | DMSO | 1 mg/mL warmed with 50ºC water bath (2.5 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. |
製品説明 | Dorsomorphin is a potent, reversible, selective AMPK inhibitor with Ki of 109 nM in cell-free assays, exhibiting no significant inhibition of several structurally related kinases including ZAPK, SYK, PKCθ, PKA, and JAK3. Dorsomorphin selectively inhibits the BMP type I receptors ALK2, ALK3 and ALK6. Dorsomorphin is used in promoting specific cell differentiation and inducing cancer cell line autophagy. For animal testing, the water-soluble S7306 Dorsomorphin (Compound C) 2HCl is recommended. |
---|---|
in vitro | Dorsomorphin inhibits ACC inactivation by either AICAR or metformin, and also attenuates AICAR and metformin’s effect to increase fatty acid oxidation or suppress lipogenic genes in hepatocytes. [1] Inhibition of AMPK activity by Dorsomorphin almost completely inhibits autophagic proteolysis in HT-29 cells. [2] In addition, Dorsomorphin selectively inhibits the BMP type I receptors ALK2, ALK3 and ALK6, and thus blocks BMP-mediated SMAD1/5/8 phosphorylation, target gene transcription and osteogenic differentiation. [3] |
in vivo | Dorsomorphin (10 mg/kg) reduces basal levels of hepcidin expression and increases serum iron concentrations in adult mice. [3] Dorsomorphin (0.2 mg/kg, i.v.) significantly reduces VCAM-1 and ICAM-1 expression in the thoracic aorta of LPS-treated rats. [4] |
キナーゼアッセイ | AMPK partial purification and in vitro kinase assay. | |
---|---|---|
Liver AMPK is partially purified from male SD rats to the blue-Sepharose step. The 100-μl reaction mixture contains 100 μM AMP, 100 μM ATP (0.5 μCi 33P-ATP per reaction), and 50 μM SAMS in a buffer (40 mM HEPES, pH 7.0, 80 mM NaCl, 0.8 mM EDTA, 5 mM MgCl2, 0.025% BSA, and 0.8 mM DTT). The reaction is initiated with addition of the enzyme. After 30-minute incubation at 30°C, the reaction is stopped by addition of 80 μl 1% H3PO4. Aliquots (100 μl) are transferred to 96-well MultiScreen plates. The plate is washed three times with 1% H3PO4 followed by detection in a Top-count. The in vitro AMPK inhibition data obtained with compound C — (6-[4-(2-Piperidin-1-yl-ethoxy)-phenyl)]-3-pyridin-4-yl-pyyrazolo[1,5-a] pyrimidine — are fit to the following equation for competitive inhibition by nonlinear regression using a least-squares Marquardt algorithm in a computer program written by N. Thornberry of Merck Research Laboratories: Vi/Vo = (Km + S)/[S + Km × (1 + I/Ki)], where Vi is the inhibited velocity, Vo is the initial velocity, S is the substrate (ATP) concentration, Km is the Michaelis constant for ATP, I is the inhibitor (compound C) concentration, and Ki is the dissociation constant for compound C. | ||
細胞アッセイ | 細胞株 | Cell-free assays |
濃度 | 109 nM | |
反応時間 | ||
実験の流れ | ||
動物実験 | 動物モデル | Iron-replete mice |
投薬量 | ~10 mg/kg | |
投与方法 | i.v. |
, , J Cell Physiol, 2017, 232(7):1893-1906
, , Clin Exp Pharmacol Physiol, 2016, 43(1):125-34.
Data from [Data independently produced by , , Oncotarget, 2016, 6(41):43605-19.]
Progranulin promotes regulatory T cells plasticity by mitochondrial metabolism through AMPK/PGC-1α pathway in ARDS [ Clin Immunol, 2024, 261:109940] | PubMed: 38365048 |
Ultrasound-targeted microbubble technology facilitates SAHH gene delivery to treat diabetic cardiomyopathy by activating AMPK pathway [ iScience, 2024, 27(2):108852] | PubMed: 38303706 |
Tiaogan daozhuo formula attenuates atherosclerosis via activating AMPK -PPARγ-LXRα pathway [ J Ethnopharmacol, 2024, 324:117814] | PubMed: 38286155 |
Cardioprotective effects of asiaticoside against diabetic cardiomyopathy: Activation of the AMPK/Nrf2 pathway [ J Cell Mol Med, 2024, 28(2):e18055] | PubMed: 38113341 |
Hypoglycemic effects of dracorhodin and dragon blood crude extract from Daemonorops draco [ Bot Stud, 2024, 65(1):8] | PubMed: 38446324 |
Metformin improves memory via AMPK/mTOR-dependent route in a rat model of Alzheimer's disease [ Iran J Basic Med Sci, 2024, 27(3):360-365.] | PubMed: 38333746 |
Transient naive reprogramming corrects hiPS cells functionally and epigenetically [ Nature, 2023, 620(7975):863-872] | PubMed: 37587336 |
Transient naive reprogramming corrects hiPS cells functionally and epigenetically [ Nature, 2023, 620(7975):863-872] | PubMed: 37587336 |
Dysregulated Lipid Synthesis by Oncogenic IDH1 Mutation Is a Targetable Synthetic Lethal Vulnerability [ Cancer Discov, 2023, 13(2):496-515] | PubMed: 36355448 |
ADP-dependent glucokinase controls metabolic fitness in prostate cancer progression [ Mil Med Res, 2023, 10(1):64] | PubMed: 38082365 |
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。