AZD8055

製品コードS1555 バッチS155509

印刷

化学情報

Chemical Structure Synonyms N/A Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C25H31N5O4
分子量 465.54 CAS No. 1009298-09-2
Solubility (25°C)* 体外 DMSO 93 mg/mL warmed with 50ºC water bath (199.76 mM)
Ethanol 3.5 mg/mL (7.51 mM)
Water 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 AZD8055 is a novel ATP-competitive mTOR inhibitor with IC50 of 0.8 nM in MDA-MB-468 cells with excellent selectivity (∼1,000-fold) against PI3K isoforms and ATM/DNA-PK. AZD8055 induces caspase-dependent apoptosis and also induces autophagy. Phase 1.
in vitro AZD8055 shows low activity (∼1,000-fold) against all PI3K isoforms (α, β, γ, δ) and other members of the PI3K-like kinase family (ATM and DNA-PK). AZD8055 inhibits the phosphorylation of mTORC1 (p70S6K and 4E-BP1) as well as phosphorylation of the mTORC2 (Akt) and downstream proteins. The rapamycin-resistant T37/46 phosphorylation sites on 4E-BP1 can be fully inhibited by AZD8055, resulting in significant inhibition of cap-dependent translation. AZD8055 potently inhibits proliferation in U87MG, A549 and H838 cells with IC50 of 53, 50 and 20 nM, respectively. AZD8055 also induces autophagy and increased LC3-II levels in H838 and A549 cells. [1] AZD8055 decreases AML blast cell proliferation and cell cycle progression, reduces the clonogenic growth of leukemic progenitors and induces caspase-dependent apoptosis in leukemic cells but not in normal immature CD34+ cells. [2] AZD8055 indicates inhibitory against the pediatric preclinical testing program (PPTP) cell lines with IC50 of 24.7 nM and induces significant differences in EFS distribution. [3]
in vivo AZD8055 inhibits the pS6 and pAkt in U87MG and A549 xenografts at 2.5/10 mg/kg, which leads to tumor growth inhibition. AZD8055 shows significant antitumor activity in many xenografts, including U87MG, BT474c, A549, Calu-3, LoVo, SW620, PC3 and MES-SA at a dose of 10/20 mg/kg. [1] AZD8055 induces ~40% reduction in tumour volume, accompanied by ablation of phosphorylation of Akt, S6K and SGK protein kinases. Administration of AZD8055 (5mg/kg, Bid) and SAHA (100 mg/kg/d) results in complete tumor growth inhibition in PTEN+/−LKB1+/hypo xenografts without side effects on mice by inhibition of mTORC1 and mTORC2 signaling. [4]
特徴 First drug to inhibit both types of mTOR protein.

プロトコル(参考用のみ)

キナーゼアッセイ Cell-based determinations of mTOR inhibition
A high-throughput screening cell-based assay is developed using MDA-MB-468 cells to detect mTORC1 and mTORC2 activity. Cells are exposed for 2 hours to increasing concentrations of AZD8055. At the end of the incubation period, cells are fixed, washed, and probed with antibodies against S473 pAkt or against S235/236 phosphorylated S6 (pS6). Levels of phosphorylation are assessed using an Acumen laser scanning cytometer.
細胞アッセイ 細胞株 U87MG, A549 and H838 cells
濃度 1 nM - 1 μM
反応時間 72 to 96 hours
実験の流れ Cells are exposed to AZD8055 for 72 to 96 hours and stained for cell nuclei (0.03 mg/mL Hoechst 33342) and acidic vesicles (1 μg/mL acridine orange). Images are captured at 450 and 536 nm on an ArrayScan II platform, and the percentage of acidic vesicles and the number of cells are quantified. For LC3 assessment, cells are exposed to e64d/pepstatin (10 μg/mL) for 30 to 90 min before incubation with AZD8055. Cells are lysed on ice and analyzed by immunoblotting.
動物実験 動物モデル U87MG, BT474c, A549, Calu-3, LoVo, SW620, PC3 and MES-SA U87-MG and A549 are established in pathogen-free, female nude mice (nu/nu:Alpk).
投薬量 2.5-20 mg/kg
投与方法 Oral gavage once or twice daily

カスタマーフィードバック

Data from [Data independently produced by Int J Cancer, 2014, 135(10), 2462-74]

Data from [Data independently produced by Antioxid Redox Signal, 2014, 20(9), 1382-95]

Data from [Data independently produced by Mol Cancer Ther, 2014, 13(1), 37-48]

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 CDK4/6 and XPO1 Induces Senescence With Acquired Vulnerability to CRBN-Based PROTAC Drugs [ Gastroenterology, 2024, S0016-5085(24)00062-3] PubMed: 38262581
Cancer cell genetics shaping of the tumor microenvironment reveals myeloid cell-centric exploitable vulnerabilities in hepatocellular carcinoma [ Nat Commun, 2024, 15(1):2581] PubMed: 38519484
NOP14-mediated ribosome biogenesis is required for mTORC2 activation and predicts rapamycin sensitivity [ J Biol Chem, 2024, S0021-9258(24)00057-7] PubMed: 38272224
A TREM2-activating antibody with a blood-brain barrier transport vehicle enhances microglial metabolism in Alzheimer's disease models [ Nat Neurosci, 2023, none] PubMed: 36635496
Loss of NF1 in Melanoma Confers Sensitivity to SYK Kinase Inhibition [ Cancer Res, 2023, 83(2):316-331] PubMed: 36409827
A multiplexed in vivo approach to identify driver genes in small cell lung cancer [ Cell Rep, 2023, 42(1):111990] PubMed: 36640300
Rational combination of SHP2 and mTOR inhibition for the treatment of hepatocellular carcinoma [ Mol Oncol, 2023, none] PubMed: 36650715
Unique Metabolic Contexts Sensitize Cancer Cells and Discriminate between Glycolytic Tumor Types [ Cancers (Basel), 2023, 15(4)1158] PubMed: 36831501
Integrative Analyses Reveal the Anticancer Mechanisms and Sensitivity Markers of the Next-Generation Hypomethylating Agent NTX-301 [ Cancers (Basel), 2023, 15(6)1737] PubMed: 36980623
Multiplex Protein Imaging through PACIFIC: Photoactive Immunofluorescence with Iterative Cleavage [ ACS Bio Med Chem Au, 2023, 3(3):283-294] PubMed: 37363079

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。

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