AZ20

Catalog No.S7050 Batch:S705001

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Technical Data

Formula

C21H24N4O3S
Molecular Weight 412.51 CAS No. 1233339-22-4
Solubility (25°C)* In vitro DMSO 83 mg/mL (201.2 mM)
Ethanol 3 mg/mL (7.27 mM)
Water Insoluble
In vivo (Add solvents to the product individually and in order)
Clear solution
5% DMSO 95% Corn oil
0.41mg/ml Taking the 1 mL working solution as an example, add 50 μL of 8.2 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results. 
Clear solution
5%DMSO 40%PEG300 5%Tween80 50%ddH2O
5.0mg/ml Taking the 1 mL working solution as an example, add 50 μL of 100 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results. 
* <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.)

Preparing Stock Solutions

Biological Activity

Description AZ20 is a novel potent and selective inhibitor of ATR kinase with IC50 of 5 nM in a cell-free assay, 8-fold selectivity over mTOR.
Targets
ATR [2]
(Cell-free assay)		 mTOR [2]
(Cell-free assay)
5 nM 38 nM
In vitro AZ20 shows good selectivity against all of the PI3K isoforms together with ATM and DNA-PK. [2] In vitro, AZ20 decreases pChk1 Ser345, pChk1 Ser317 and pChk1 Ser296 levels in a concentration-dependent manner. Prolonged exposure with AZ20 increases γH2AX pan-nuclear staining, indicative of replication stress. This is associated with S-phase arrest and increase in phospho-histone H3. AZ20 induces growth inhibition and cell death in vitro and its profile of activity is distinct from other cytotoxic agents. The cytotoxic effect of AZ20 can be increased in combination with the selective ATM inhibitor KU-60019. [1]
In vivo Female nude mice bearing LoVo tumors are treated with AZ20 orally at a dose of 25 mg/kg twice daily or 50 mg/kg once daily for 13 days, led to significant tumor growth inhibition. [2] This is associated with a persistent elevation of γH2AX pan-nuclear staining in xenograft tissue, but a transient increase in mouse bone marrow at therapeutic doses, suggesting a favourable therapeutic index. [1] AZ20 is assessed for drug−drug interaction (DDI) potential specifically from inhibition of cytochrome P450 enzymes. AZ20 is found to inhibit the cytochrome 3A4-mediated metabolism of midazolam by 50% at 10 μM. AZ20 has respectable bioavailability in a low dose rat PK study. [2]
Features ATR-selective inhibitor with high permeability and good stability.

Protocol (from reference)

Animal Study:[2]
  • Animal Models

    LoVo colorectal adenocarcinoma xenografts

  • Dosages

    25 mg/kg twice daily and 50 mg/kg once daily

  • Administration

    orally

Customer Product Validation

Data from [Data independently produced by , , Molecular Oncology, 2016, 1-13.]

Data from [Data independently produced by , , Sci Rep, 2017, 7:41950]

Data from [Data independently produced by , , Oncotarget, 2016, 7(18):25885-901]

Data from [Data independently produced by , , Oncol Rep, 2018, 37(6):3377-3386]

Selleck's AZ20 has been cited by 45 publications

OTUD5 limits replication fork instability by organizing chromatin remodelers [ Nucleic Acids Res, 2023, 51(19):10467-10483] PubMed: 37713620
Actionable cancer vulnerability due to translational arrest, p53 aggregation and ribosome biogenesis stress evoked by the disulfiram metabolite CuET [ Cell Death Differ, 2023, 10.1038/s41418-023-01167-4] PubMed: 37142656
OTUD5 limits replication fork instability by organizing chromatin remodelers [ Nucleic Acids Res, 2023, gkad732] PubMed: 37713620
ATR protects ongoing and newly assembled DNA replication forks through distinct mechanisms [ Cell Rep, 2023, 42(7):112792] PubMed: 37454295
Adeno-Associated Virus Monoinfection Induces a DNA Damage Response and DNA Repair That Contributes to Viral DNA Replication [ mBio, 2023, e0352822.] PubMed: 36719192
Inhibition of DNA-dependent protein kinase catalytic subunit boosts rAAV transduction of polarized human airway epithelium [ Mol Ther Methods Clin Dev, 2023, 31:101115] PubMed: 37841417
ATR activation by Cr-DNA damage is a major survival response establishing late S and G2 checkpoints after Cr-VI) exposure [ Toxicol Appl Pharmacol, 2023, 477:116696] PubMed: 37734571
Comprehensive mapping of cell fates in microsatellite unstable cancer cells support dual targe6ng of WRN and ATR [ bioRxiv, 2023, 2023.07.28.550976] PubMed: 37662356
The TRESLIN-MTBP complex couples completion of DNA replication with S/G2 transition [ Mol Cell, 2022, 82(18):3350-3365.e7] PubMed: 36049481
Phosphoproteomics of ATR signaling in mouse testes [ Elife, 2022, 11e68648] PubMed: 35133275

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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.

NOT FOR HUMAN, VETERINARY DIAGNOSTIC OR THERAPEUTIC USE.