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Formula | C25H31N5O4 |
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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 | ||||||
In vivo (Add solvents to the product individually and in order) |
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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. * Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.) |
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. | ||||
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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. |
Kinase Assay:[1] |
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Cell Assay:[1] |
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Animal Study:[1] |
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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]
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 |
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