Item

Specification

Appearance

Light yellow to yellow solid

Solubility

DMSO: 50 mg/mL warm (107.4 mM); Water Insoluble;Ethanol: 3 mg/mL (6.44 mM)

Content

>98%

Product Description

AZD8055 is a novel ATP competitive mTOR inhibitor with an IC50 of 0.8 nM. It acts on PI3K subtypes and ATM/DNA-PK with excellent selectivity (approximately 1000 fold).

Target point

overall length mTOR

Truncated mTOR

IC50

0.8 nM

0.13 nM

In vitro research

AZD 8055 exhibits low activity when acting on all PI3K subtypes (α, β, γ, δ) and other close PI3K kinase families (ATM and DNA-PK). It inhibits phosphorylation of mTORC1 (p70S6K and 4E-BP1), mTORC2 (AKT), and downstream proteins. It completely inhibits the T37/46 phosphorylation site of 4E-BP1 against Rapamycin, resulting in significant inhibition of cap dependent translation. It effectively inhibits the proliferation of U87MG, A549, and H838 cells, with IC50 values of 53, 50, and 20 nM, respectively. It acts on H838 and A549 cells, inducing autophagy and increasing LC3-II levels. It reduces leukemia cell proliferation and cell cycle progression, decreases clonal growth of leukemia progenitor cells, and induces caspase dependent apoptosis in leukemia cells, but does not produce this inducing effect when applied to normal immature CD34+cells. It inhibits the Pediatric Preclinical Testing Program (PPTP) cell line with an IC50 of 24.7 nM and induces significant differences in EFS distribution.

In vivo research

AZD-8055 acts on U87MG and A549 transplanted tumors at a dose of 2.5/10 mg/kg to inhibit pS6 and pAKT, resulting in inhibited tumor growth. It showed significant anti-cancer activity when treated with a dose of 10/20 mg/kg for various transplant tumors including U87MG, BT474c, A549, Calu-3, LoVo, SW620, PC3, and MES-SA. It induces a decrease in tumor volume of approximately 40%, accompanied by resection of AKT, S6K, and SGK protein kinase phosphorylation. Treatment of PTEN+/- LKB1+/hypo transplanted tumors with AZD8055 (5mg/kg, twice daily) and SAHA (100 mg/kg/day) resulted in complete inhibition of tumor growth and no side effects on mTORC1 and mTORC2 signaling inhibition in mice.

Characteristic

It is the first drug to inhibit two types of mTOR proteins and is believed to be more effective than previous mTOR inhibitors.

1 mg

5 mg

10 mg

1 mM

2.1480 mL

10.7402 mL

21.4804 mL

5 mM

0.4296 mL

2.1480 mL

4.2961 mL

10 mM

0.2148 mL

1.0740 mL

2.1480 mL

50 mM

0.0430 mL

0.2148 mL

0.4296 mL

Kinase experiment

Cell based assay for inhibiting mTOR:

Using high-throughput screening cell detection method, MDA-MB-468 cells were used to measure mTORC1 and mTORC2 activity. Treat cells with increased concentration of AZD8055 for 2 hours. At the end of incubation, the cells were fixed, washed, and detected with p-Akt (S473) antibody and p-S6 (S235/236) antibody. Use a laser scanner to detect phosphorylation levels.

Cell experiment

Cell lines: U87MG, A549, and H838 cells

Concentrations: Dissolve in DMSO as a 10 mM stock solution, 0.001-1.0 μ M

Incubation Time: 72 to 96 hours

Method: Treat cells with AZD 8055 for 72 to 96 hours, stain cell nuclei with 0.03 mg/mL Hoechst 33342, and stain acidic vesicles with 1 μ g/mL acridine orange. Images were obtained at 450 and 536 nanometers using the ArrayScan II platform, and the percentage of acidic vesicles and cell count were measured. Perform LC3 evaluation, treat cells with 10 μ g/mL e64d/peptidoglycan for 30 to 90 minutes, and then incubate with AZD8055. Cells were dissolved on ice and analyzed by immunoblotting.

Animal experiments

Animal Models: U87MG, BT474c, A549, Calu-3, LoVo, SW620, PC3, and MES-SA U87-MG and A549 cells were established in pathogen free female nude mice (nu/nu: Alpk).

Formulation: Dissolve in captisol (CyDex, pH 3.0) and dilute to a final captisol concentration of 30% (w/v).

Dosages: 2.5-20 mg/kg

Administration: Oral feeding, 1-2 times a day.

Packing：

1kg/foil bag;5kg/carton;25kg/fiber drum; or packing as your request.

Customization:

l Customized logo

l Customized packaging

l Graphic customization

Shipping：

By Courier; By Air or By Sea, according to your demands