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化学情報
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Synonyms | N/A | Storage (From the date of receipt) |
3 years -20°C powder 1 years -80°C in solvent |
| 化学式 | C21H16FN7 |
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| 分子量 | 385.4 | CAS No. | 1608125-21-8 | |
| Solubility (25°C)* | 体外 | DMSO | 77 mg/mL (199.79 mM) | |
| Ethanol | 77 mg/mL (199.79 mM) | |||
| Water | Insoluble | |||
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* <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. |
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溶剤液（一定の濃度）を調合する
生物活性
| 製品説明 | AMG319 is a potent and selective PI3Kδ inhibitor with IC50 of 18 nM, >47-fold selectivity over other PI3Ks. Phase 2. |
|---|---|
| in vitro | AMG319 inhibits anti-IgM/CD40L-induced B cell proliferation with IC50 of 8.6 nM and reduces pAkt level with IC50 of 1.5 nM. AMG319 also inhibits anti-IgD-induce CD-69 expression in HWB. [1] |
| in vivo | In female Lewis rats, AMG319 (3 mg/kg, p.o.) inhibits the KLH-induced inflammatory response by 88%. In the transgenic (IgMm) mice, AMG319 (, p.o.) inhibits in vivo pAKT with IC50 of 1.9 nM. [1] |
プロトコル(参考用のみ)
| キナーゼアッセイ | PI3K Enzyme Assays | |
|---|---|---|
| A PI3K Alphascreen assay is used to measure the activity of a panel of four phosphoinositide 3-kinases: PI3Kα, PI3Kβ, PI3Kγ, and PI3Kδ. Enzyme reaction buffer is prepared using sterile water and 50 mM Tris-HCl, pH 7, 14 mM MgCl2, 2 mM sodium cholate, and 100 mM NaCl. 2 mM DTT is added fresh on the day of the experiment. The Alphascreen buffer is made using sterile water and 10 mM Tris-HCl, pH 7.5, 150 mM NaCl, 0.10% Tween 20, and 30 mM EDTA. Then 1 mM DTT is added fresh on the day of the experiment. Compound source plates used for this assay are 384-well Greiner clear polypropylene plates containing test compounds at 5 mM and diluted 1:2 over 22 concentrations. Columns 23 and 24 contained only DMSO, as these wells comprised the positive and negative controls, respectively. Source plates are replicated by transferring 0.5 μL per well into 384-well Optiplates. Each PI3K isoform is diluted in enzyme reaction buffer to 2× working stocks. PI3Kα is diluted to 1.6 nM, PI3Kβ is diluted to 0.8 nM, PI3Kγ is diluted to 15 nM, and PI3Kδ is diluted to 1.6 nM. PI(4,5)P2 is diluted to 10 μM, and ATP was diluted to 20 μM. This 2× stock is used in the assays for PI3Kα and PI3Kβ. For assay of PI3Kγ and PI3Kδ, PI(4,5)P2 is diluted to 10 μM and ATP was diluted to 8 μM to prepare a similar 2× working stock. Alphascreen reaction solutions are made using beads from the anti-GST Alphascreen kit. Two 4× working stocks of the Alphascreen reagents are made in Alphascreen reaction buffer. In one stock, biotinylated-IP4 is diluted to 40 nM and streptavadin-donor beads are diluted to 80 μg/mL. In the second stock, PIP3-binding protein is diluted to 40 nM and anti-GST-acceptor beads were diluted to 80 μg/mL. As a negative control, a reference inhibitor at a concentration ≫Ki (40 μM) is included in column 24 as a negative (100% inhibition) control. Using a 384-well Multidrop, 10 μL/well of 2× enzyme stock is added to columns 1–24 of the assay plates for each isoform. An amount of 10 μL/well of the appropriate substrate 2× stock (containing 20 μM ATP for the PI3Kα and -β assays and containing 8 μM ATP for the PI3Kγ and -δ assays) is then added to columns 1–24 of all plates. Plates are then incubated at room temperature for 20 min. In the dark, 10 μL/well of the donor bead solution is added to columns 1–24 of the plates to quench the enzyme reaction. The plates are incubated at room temperature for 30 min. Still in the dark, 10 μL/well of the acceptor bead solution is added to columns 1–24 of the plates. The plates are then incubated in the dark for 1.5 h. The plates are read on an Envision multimode plate reader using a 680 nm excitation filter and a 520–620 nm emission filter. | ||
| 細胞アッセイ | 細胞株 | PBMCs |
| 濃度 | ||
| 反応時間 | 72 h | |
| 実験の流れ | B cells are purified from human peripheral blood mononuclear cells (PBMCs) by negative selection. Approximately 3 × 104 purified B cells per well are seeded into a 96-well plate. Compounds are dissolved in DMSO at a concentration of 10 mM, and a 10-point, 3-fold serial dilution of the compound is carried out in DMSO. Then 0.5 μL of compound is added to each well in duplicates so that the final DMSO concentration is 0.25% and the highest compound concentration is 10 μM. After preincubating for 30 min, B cells are treated with 2 μg/mL of anti-human IgM antibody plus 300 ng/mL human CD40L or 5 ng/mL human IL-4 plus 200 ng/mL of CD40L as a counterscreen to evaluate the off-target effects. The plates are incubated at 37 °C and 5% CO2 for 72 h, then pulsed with 0.5 μCi per well 3H thymidine for 18 h, and B cells are collected to count the incorporation of 3H thymidine. | |
| 動物実験 | 動物モデル | Female Lewis rats |
| 投薬量 | ~3 mg/kg | |
| 投与方法 | p.o. | |
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：
| Impaired airway epithelial barrier integrity was mediated by PI3Kδ in a mouse model of lipopolysaccharide-induced acute lung injury [ Int Immunopharmacol, 2021, 95:107570] | PubMed: 33773208 |
| Distinct roles of PI3Kδ and PI3Kγ in a toluene diisocyanate-induced murine asthma model [ Toxicology, 2021, 454:152747] | PubMed: 33711354 |
| Topical Application of the PI3Kβ-Selective Small Molecule Inhibitor TGX-221 Is an Effective Treatment Option for Experimental Epidermolysis Bullosa Acquisita [ Front Med (Lausanne), 2021, 8:713312] | PubMed: 34557502 |
| Topical Application of the PI3Kβ-Selective Small Molecule Inhibitor TGX-221 Is an Effective Treatment Option for Experimental Epidermolysis Bullosa Acquisita [ Front Med (Lausanne), 2021, 8:713312] | PubMed: 34557502 |
| In vivo microscopy reveals macrophage polarization locally promotes coherent microtubule dynamics in migrating cancer cells [ Nat Commun, 2020, 11(1):3521] | PubMed: 32665556 |
| Screening of PI3K-Akt-targeting Drugs for Silkworm against Bombyx mori Nucleopolyhedrovirus. [ Molecules, 2019, 24(7)] | PubMed: 30939726 |
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。