AZ32

Catalog No.S8729

AZ32 Chemical Structure

Molecular Weight(MW): 328.37

AZ32 is a specific inhibitor of the ATM kinase that possesses good BBB penetration in mouse with an IC50 value of <0.0062 μM for ATM enzyme. It shows adequate selectivity over ATR and also has high cell permeability.

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Biological Activity

Description AZ32 is a specific inhibitor of the ATM kinase that possesses good BBB penetration in mouse with an IC50 value of <0.0062 μM for ATM enzyme. It shows adequate selectivity over ATR and also has high cell permeability.
Targets
ATM [1]
(Cell-free assay)
<0.0062 μM
In vitro

AZ32 blocks the DNA damage response (DDR) and radiosensitized GBM cells in vitro. AZ32 shows moderate potency against ATM in cell (IC50 = 0.31 μM) and adequate selectivity over ATR, while also having high cell permeability[1].

In vivo

AZ32, with enhanced blood-brain barrier (BBB) penetration, was highly efficient in vivo as radiosensitizer in syngeneic and human, orthotopic mouse glioma model compared with AZ31. AZ32 is the first ATMi with oral bioavailability shown to radiosensitize glioma and improve survival in orthotopic mouse models. Following a single oral dose of AZ32 (200 mg/kg) in mice, the free brain concentrations of AZ32 was in excess of the cellular IC50 for approximately 22 hr. AZ32 has enhanced BBB penetration at 8.7-fold and improved brain coverage over AZ31 but with reduced ATM selectivity[1].

Protocol

Cell Research:

[1]

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  • Cell lines: U1242 cells
  • Concentrations: 3 μM
  • Incubation Time: 48 h
  • Method:

    Human glioma U1242 cells were treated with AZ32 (3 μM) and radiation (2 Gy) or left untreated. At 48 hrs the cells were fixed and processed for ICC using anti-γ-tubulin (centrosomes) and -α-tubulin (microtubules). Cells were counterstained with DAPI to visualize nuclei.


    (Only for Reference)
Animal Research:

[1]

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  • Animal Models: orthotopic GL261 glioma model (GL261/luc-red cells intracranially injected into C57bl6 mice)
  • Formulation: hydroxypropyl-methyl cellulose (0.5%w/v)/0.1%w/v polysorbate-80
  • Dosages: 200 mg/kg
  • Administration: p.o.
    (Only for Reference)

Solubility (25°C)

In vitro DMSO 66 mg/mL (200.99 mM)
Ethanol 7 mg/mL (21.31 mM)
Water 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.

Chemical Information

Molecular Weight 328.37
Formula

C20H16N4O

CAS No. No
Storage powder
in solvent
Synonyms N/A

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Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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ATM/ATR Signaling Pathway Map

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID