Home PI3K/Akt/mTOR ATM/ATR inhibitor AZ20 For research use only.

AZ20

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.

AZ20 Chemical Structure

AZ20 Chemical Structure

CAS: 1233339-22-4

Selleck's AZ20 has been cited by 44 publications

Purity & Quality Control

Batch: S705001 DMSO] 83 mg/mL] false] Ethanol] 3 mg/mL] false] Water] Insoluble] false Purity: 99.92%
99.92

AZ20 Related Products

Signaling Pathway

ATM/ATR Signaling Pathways

ATM/ATR Signaling Pathway

Choose Selective ATM/ATR Inhibitors

Cell Data

Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
HT29 Function assay 1 hr Inhibition of ATR-mediated CHK1 phosphorylation at serine 345 in human HT29 cells after 1 hr in presence of 4-nitroquinoline 1-oxide, IC50=0.05μM 23394205
LoVo Growth inhibition assay 72 hrs Growth inhibition of human LoVo cells after 72 hrs by MTS assay, GI50=0.2μM 23394205
MDA-MB-468 Function assay Inhibition of mTOR-mediated AKT phosphorylation at serine 473 in human MDA-MB-468 cells, IC50=2.4μM 23394205
LoVo Antitumor assay 50 mg/kg 13 days Antitumor activity against human LoVo cells xenografted in Swiss nu/nu mouse assessed as tumor growth inhibition at 50 mg/kg, po qd for 13 days relative to control 23394205
LoVo Antitumor assay 25 mg/kg 13 days Antitumor activity against human LoVo cells xenografted in Swiss nu/nu mouse assessed as tumor growth inhibition at 25 mg/kg, po bid for 13 days relative to control 23394205
HT29 Function assay 60 mins Inhibition of ATR in human HT29 cells after 60 mins by Hoechst 33258 staining-based assay, IC50=0.061μM 30346772
LoVo Cytotoxicity assay 72 hrs Cytotoxicity against human LoVo cells after 72 hrs by MTS assay, GI50=0.2μM 30346772
MDA-MB-468 Function assay Inhibition of mTOR in human MDA-MB-468 cells assessed as decrease in 70S6K S235/236 phosphorylation, IC50=0.72μM 30346772
HT-29 Cytotoxicity assay 72 hrs Cytotoxicity against human HT-29 cells after 72 hrs by MTS assay, GI50=0.97μM 30346772
LoVo Function assay 25 mg/kg 8 hrs Plasma concentration in Swiss nu/nu mouse xenografted with human LoVo cells at 25 mg/kg, po bid after 8 hrs, Cp=1.8μM 30346772
MDA-MB-468 Function assay Inhibition of mTOR in human MDA-MB-468 cells assessed as decrease in AKT phosphorylation at S473 residue, IC50=2.4μM 30346772
LoVo Function assay 50 mg/kg 8 hrs Plasma concentration in Swiss nu/nu mouse xenografted with human LoVo cells at 50 mg/kg, po qd after 8 hrs, Cp=3.5μM 30346772
Click to View More Cell Line Experimental Data

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.
Features ATR-selective inhibitor with high permeability and good stability.
Targets
ATR [2]
(Cell-free assay)		 mTOR [2]
(Cell-free assay)
5 nM 38 nM
In vitro
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]
Experimental Result Images Methods Biomarkers Images PMID
Growth inhibition assay IC50 28176818
Western blot p-CDK1 / CDK1 / p-CDK2 / CDK2 γH2AX / RRM1 / RRM2 28176818
In Vivo
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]
Animal Research Animal Models LoVo colorectal adenocarcinoma xenografts
Dosages 25 mg/kg twice daily and 50 mg/kg once daily
Administration orally

Chemical Information & Solubility

Molecular Weight 412.51 Formula

C21H24N4O3S
CAS No. 1233339-22-4 SDF Download AZ20 SDF
Smiles CC1COCCN1C2=NC(=NC(=C2)C3(CC3)S(=O)(=O)C)C4=C5C=CNC5=CC=C4
Storage (From the date of receipt)

In vitro
Batch:

DMSO : 83 mg/mL ( (201.2 mM)； Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Ethanol : 3 mg/mL

Water : Insoluble


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In vivo
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Tech Support

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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Frequently Asked Questions

Question 1:
If I want to completely block the kinase activity from the in vitro cell lines, how much concentration I should use?

Answer:
IC50 5nM was quoted from a previous publication in which the author tested IC50 of AZ20 in cell free assay. In cell culture, many factors, such as membrane permeability and target protein concentration, may affect the efficiency. Each cell line responses to the same compound differently and it is very difficult to predict the optimized concentration simply based on cell free data. In cell culture experiment, the required concentration is usually higher. We recommend that you perform a pilot experiment and test different concentrations (50nM to 500uM) to get the optimized condition.

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