AZD-8055

SKU: orb1307308

Description

AZD8055 is a potent and selective ATP-competitive mTOR inhibitor, exhibiting an IC50 of 0.8 nM in cellular assays with approximately 1000-fold selectivity over PI3K isoforms. It is widely used in preclinical research to investigate mTOR signaling in cancer biology, demonstrating efficacy in both in vitro and in vivo models for oncology studies.

Research Area

Cell Biology, Signal Transduction

Key Properties

• CAS Number: 1009298-09-2
• MW: 465.54
• Purity: 99.69% (May vary between batches)
• Formula: C₂₅H₃₁N₅O₄
• SMILES: C[C@@H]1N(C=2C3=C(N=C(N2)N4[C@@H](C)COCC4)N=C(C=C3)C5=CC(CO)=C(OC)C=C5)CCOC1
• Target: Autophagy,mTOR,Apoptosis
• Solubility: 10% DMSO+40% PEG300+5% Tween 80+45% Saline:4.5 mg/mL (9.67 mM);H2O:< 1 mg/mL (insoluble or slightly soluble);DMSO:91 mg/mL (195.47 mM);Ethanol:3 mg/mL (6.44 mM)

Bioactivity

• Target IC50:
  mTOR:0.8 nM (MDA-MB-468 cells)
• In Vivo:
  In vivo, AZD8055 induces a dose-dependent pharmacodynamic effect on phosphorylated S6 and phosphorylated AKT at plasma concentrations leading to tumor growth inhibition . AZD8055 administration could significantly decrease the IL-1β and TNF-α concentrations. Rats subjected to SAH + vehicle group demonstrated histological evidence of apoptosis compared with the sham group. The group treated with AZD8055 demonstrated a significant decrease in apoptosis ratio in the rat brain sample. In addition, in SAH group, the number of fluoro-jade B-positive cells clearly increased compared with the sham group. And the number of fluoro-jade B-positive cells decreased significantly in the SAH + rapamycin group and SAH + AZD8055 group .
• In Vitro:
  AZD8055 inhibits the phosphorylation of mTORC1 substrates p70S6K and 4E-BP1 as well as phosphorylation of the mTORC2 substrate AKT and downstream proteins. The rapamycin-resistant T37/46 phosphorylation sites on 4E-BP1 were fully inhibited by AZD8055, resulting in significant inhibition of cap-dependent translation. In vitro, AZD8055 potently inhibits proliferation and induces autophagy in H838 and A549 cells . In vitro, the median relative IC50 for AZD8055 against the PPTP cell lines was 24.7 nM. Relative I/O values >0% were observed in 8 cell lines and 15 cell lines showed Relative I/O values ranging from -4.7 to -92.2% .
• Cell Research:
  For growth inhibition and acridine staining, cells were exposed to increasing concentrations of AZD8055 for 72 to 96 h and stained for cell nuclei (0.03 mg/mL Hoechst 33342) and acidic vesicles (1 μg/mL acridine orange). Images were captured at 450 and 536 nm on an ArrayScan II platform, and the percentage of acidic vesicles and the number of cells were quantified. For LC3 assessment, cells were exposed to e64d/pepstatin (10 μg/mL) for 30 to 90 min before incubation with AZD8055. Cells were lysed on ice and analyzed by immunoblotting .
• Animal Research:
  Tumor cells (10^6 for U87-MG, 5 × 10^6 for A549) were injected s.c. in a volume of 0.1 mL, and mice were randomized into control and treatment groups when tumor size reached 0.2 cm^3. AZD8055 was formulated in 30% (w/v) captisol (pH 3.0). The control group received the vehicle only. Tumor volumes (measured by caliper), animal body weight, and tumor condition were recorded twice weekly for the duration of the study. The tumor volume was calculated (taking length to be the longest diameter across the tumor and width to be the corresponding perpendicular diameter) using the following formula: (length × width) × √(length × width) × (π/6) .

Storage & Handling

• Storage: Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

mTOR, inhibit, Inhibitor, Mammalian target of Rapamycin, Apoptosis, Autophagy, AZD8055, AZD-8055, AZD 8055

Compound Identifiers

PubChem CID

25262965