AZ20ATR inhibitor,potent and selective CAS# 1233339-22-4 |
Quality Control & MSDS
Number of papers citing our products
Chemical structure
3D structure
| Cas No. | 1233339-22-4 | SDF | Download SDF |
| PubChem ID | 46244454 | Appearance | Powder |
| Formula | C21H24N4O3S | M.Wt | 412.51 |
| Type of Compound | N/A | Storage | Desiccate at -20°C |
| Solubility | DMSO : ≥ 100 mg/mL (242.42 mM) *"≥" means soluble, but saturation unknown. | ||
| Chemical Name | (3R)-4-[2-(1H-indol-4-yl)-6-(1-methylsulfonylcyclopropyl)pyrimidin-4-yl]-3-methylmorpholine | ||
| SMILES | CC1COCCN1C2=NC(=NC(=C2)C3(CC3)S(=O)(=O)C)C4=C5C=CNC5=CC=C4 | ||
| Standard InChIKey | SCGCBAAYLFTIJU-CQSZACIVSA-N | ||
| Standard InChI | InChI=1S/C21H24N4O3S/c1-14-13-28-11-10-25(14)19-12-18(21(7-8-21)29(2,26)27)23-20(24-19)16-4-3-5-17-15(16)6-9-22-17/h3-6,9,12,14,22H,7-8,10-11,13H2,1-2H3/t14-/m1/s1 | ||
| General tips | For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months. We recommend that you prepare and use the solution on the same day. However, if the test schedule requires, the stock solutions can be prepared in advance, and the stock solution must be sealed and stored below -20℃. In general, the stock solution can be kept for several months. Before use, we recommend that you leave the vial at room temperature for at least an hour before opening it. |
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| About Packaging | 1. The packaging of the product may be reversed during transportation, cause the high purity compounds to adhere to the neck or cap of the vial.Take the vail out of its packaging and shake gently until the compounds fall to the bottom of the vial. 2. For liquid products, please centrifuge at 500xg to gather the liquid to the bottom of the vial. 3. Try to avoid loss or contamination during the experiment. |
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| Shipping Condition | Packaging according to customer requirements(5mg, 10mg, 20mg and more). Ship via FedEx, DHL, UPS, EMS or other couriers with RT, or blue ice upon request. | ||
| Description | Potent and selective ATR kinase inhibitor (IC50 = 5 nM). Exhibits 7.6-fold selectivity over mTOR and selectivity over a panel of 442 kinases, including ATM kinase, PI3-K isoforms, and DNA-PK. Inhibits cell growth in cell lines with high baseline levels of replication stress. Displays antitumor effects in vivo. |
AZ20 Dilution Calculator
AZ20 Molarity Calculator
| 1 mg | 5 mg | 10 mg | 20 mg | 25 mg | |
| 1 mM | 2.4242 mL | 12.1209 mL | 24.2418 mL | 48.4837 mL | 60.6046 mL |
| 5 mM | 0.4848 mL | 2.4242 mL | 4.8484 mL | 9.6967 mL | 12.1209 mL |
| 10 mM | 0.2424 mL | 1.2121 mL | 2.4242 mL | 4.8484 mL | 6.0605 mL |
| 50 mM | 0.0485 mL | 0.2424 mL | 0.4848 mL | 0.9697 mL | 1.2121 mL |
| 100 mM | 0.0242 mL | 0.1212 mL | 0.2424 mL | 0.4848 mL | 0.606 mL |
| * Note: If you are in the process of experiment, it's necessary to make the dilution ratios of the samples. The dilution data above is only for reference. Normally, it's can get a better solubility within lower of Concentrations. | |||||
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AZ20 is a potent and selective inhibitor of ATR. AZ20 inhibits ATR immunoprecipitated from HeLa nuclear extracts with an IC50 value of 5 nM and ATR mediated phosphorylation of Chk1 in HT29 colorectal adenocarcinoma tumor cells with an IC50 value of 50 nM.
ATR is an attractive new anticancer drug target whose inhibitors have potential as chemo- or radiation sensitizers or as monotherapy in tumors addicted to particular DNA-repair pathways.
AZ20 is the first reported inhibitor of ATR protein kinase demonstrating tumor growth inhibition in vivo and is therefore a useful probe molecule to aid further investigation of ATR tumor biology. AZ20 potently inhibited the growth of LoVo colorectal adenocarcinoma tumor cells in vitro. In the mTOR (pAKT) cell assay, AZ20 weak inhibited recombinant mTOR enzyme activity. AZ20 shows good selectivity against all of the PI3K isoforms together with ATM and DNA-PK, and when tested in a large panel of kinases, AZ20 shows very high general kinase selectivity.
Female nude mice bearing LoVo tumors were treated with AZ20 orally at a dose of 25 mg/kg twice daily or 50 mg/kg once daily for 13 days. AZ20 showed monotherapy in vivo antitumor efficacy in LoVo colorectal xenografts in nude mice.
References:
[1]. Foote KM, Blades K, Cronin A et al. Discovery of 4-{4-[(3R)-3-Methylmorpholin-4-yl]-6- [1-(methylsulfonyl)cyclopropyl]pyrimidin-2-yl}-1H-indole (AZ20): a potent and selective inhibitor of ATR protein kinase with monotherapy in vivo antitumor activity. J Med Chem. 2013 Mar 14;56(5):2125-38.
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Discovery of 4-{4-[(3R)-3-Methylmorpholin-4-yl]-6-[1-(methylsulfonyl)cyclopropyl]pyrimidin-2-y l}-1H-indole (AZ20): a potent and selective inhibitor of ATR protein kinase with monotherapy in vivo antitumor activity.[Pubmed:23394205]
J Med Chem. 2013 Mar 14;56(5):2125-38.
ATR is an attractive new anticancer drug target whose inhibitors have potential as chemo- or radiation sensitizers or as monotherapy in tumors addicted to particular DNA-repair pathways. We describe the discovery and synthesis of a series of sulfonylmorpholinopyrimidines that show potent and selective ATR inhibition. Optimization from a high quality screening hit within tight SAR space led to compound 6 (AZ20) which inhibits ATR immunoprecipitated from HeLa nuclear extracts with an IC50 of 5 nM and ATR mediated phosphorylation of Chk1 in HT29 colorectal adenocarcinoma tumor cells with an IC50 of 50 nM. Compound 6 potently inhibits the growth of LoVo colorectal adenocarcinoma tumor cells in vitro and has high free exposure in mouse following moderate oral doses. At well tolerated doses 6 leads to significant growth inhibition of LoVo xenografts grown in nude mice. Compound 6 is a useful compound to explore ATR pharmacology in vivo.
