AZD8055

Catalog No.S1555 Batch:S155510

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Technical Data

Formula

C25H31N5O4
Molecular Weight 465.54 CAS No. 1009298-09-2
Solubility (25°C)* In vitro DMSO 93 mg/mL (199.76 mM)
Ethanol 93 mg/mL (199.76 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.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

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Biological Activity

Description 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.
Targets
mTOR (truncated) [1]
(MDA-MB-468 cells)		 mTOR (full length) [1]
(MDA-MB-468 cells)
0.13 nM 0.8 nM
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]
Features First drug to inhibit both types of mTOR protein.

Protocol (from reference)

Kinase Assay:[1]
  • 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.
Cell Assay:[1]
  • Cell lines

    U87MG, A549 and H838 cells

  • Concentrations

    1 nM - 1 μM

  • Incubation Time

    72 to 96 hours

  • Method

    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.
Animal Study:[1]
  • Animal Models

    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).

  • Dosages

    2.5-20 mg/kg

  • Administration

    Oral gavage once or twice daily

Customer Product Validation

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]

Data from [Data independently produced by Oncotarget, 2014, 5(15), 6015-27]

Selleck's AZD8055 has been cited by 268 publications

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
Androgen receptor monomers and dimers regulate opposing biological processes in prostate cancer cells [ Nat Commun, 2024, 15(1):7675] PubMed: 39227594
MNK-driven eIF4E phosphorylation regulates the fibrogenic transformation of mesenchymal cells and chronic lung allograft dysfunction [ J Clin Invest, 2024, 134(16)e168393] PubMed: 39145446
The combination of breast cancer PDO and mini-PDX platform for drug screening and individualized treatment [ J Cell Mol Med, 2024, 28(9):e18374] PubMed: 38722288
NOP14-mediated ribosome biogenesis is required for mTORC2 activation and predicts rapamycin sensitivity [ J Biol Chem, 2024, S0021-9258(24)00057-7] PubMed: 38272224
Caskin2 is a novel talin- and Abi1-binding protein that promotes cell motility [ J Cell Sci, 2024, 137(9)jcs262116] PubMed: 38587458
FANCD2 expression affects platinum response and further characteristics of high grade serous ovarian cancer in cells with different genetic backgrounds [ Exp Mol Pathol, 2024, 138:104916] PubMed: 38959632
TOR kinase controls Arabidopsis shoot development by translational repression of cytokinin catabolic enzymes [ BioRxiv, 2024, 10.1101/2021.07.29.454319] PubMed: none
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

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

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