WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 406383
CAS#: 1233339-22-4
Description: AZ20 is an ATR protein kinase inhibitor, 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. AZ20 potently inhibits the growth of LoVo colorectal adenocarcinoma tumor cells in vitro and has high free exposure in mouse following moderate oral doses. AZ20 is a useful compound to explore ATR pharmacology in vivo.
MedKoo Cat#: 406383
Name: AZ20
CAS#: 1233339-22-4
Chemical Formula: C21H24N4O3S
Exact Mass: 412.15691
Molecular Weight: 412.51
Elemental Analysis: C, 61.14; H, 5.86; N, 13.58; O, 11.64; S, 7.77
Synonym: AZ20; AZ-20; AZ 20.
IUPAC/Chemical Name: (R)-4-(2-(1H-indol-4-yl)-6-(1-(methylsulfonyl)cyclopropyl)pyrimidin-4-yl)-3-methylmorpholine
InChi Key: SCGCBAAYLFTIJU-CQSZACIVSA-N
InChi Code: 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
SMILES Code: C[C@H]1N(C2=NC(C3=CC=CC4=C3C=CN4)=NC(C5(S(=O)(C)=O)CC5)=C2)CCOC1
Appearance: white solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO, not in water
Shelf Life: >2 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
| Biological target: | AZ20 is an inhibitor of ATR with an IC50 of 5 nM, and has 8-fold selectivity against mTOR (IC50=38 nM). |
| In vitro activity: | As shown in Fig. 1B and C, AZ20 treatment caused growth inhibition in a concentration-dependent manner with IC50 values ranging from 0.8 µM in HPAC cells to 2.4 µM in CFPAC-1 cells. In contrast to a previous hypothesis that p53-deficient cancer cells are more sensitive to ATR inhibition, these data showed that p53-wild-type HPAC cells responded better to AZ20 treatment compared to the p53-mutant pancreatic cancer cell lines (Fig. 1C). Reference: Oncol Rep. 2017 Jun; 37(6): 3377–3386. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6918818/ |
| In vivo activity: | Female nude mice bearing LoVo tumors were treated with compound 6 (AZ20) orally at a dose of 25 mg/kg twice daily or 50 mg/kg once daily for 13 days. Both schedules led to significant tumor growth inhibition at the end of study compared with vehicle treated controls (Figure 7). Body weight loss was in an acceptable range throughout the study, and compound 6 was generally well tolerated. Compound 6 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. Reference: J Med Chem. 2013 Mar 14;56(5):2125-38. https://pubmed.ncbi.nlm.nih.gov/23394205/ |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMF | 50.0 | 121.21 | |
| DMF:PBS (pH 7.2) (1:1) | 0.5 | 1.21 | |
| Ethanol | 4.04 | 9.79 |
The following data is based on the product molecular weight 412.51 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 1 mM | 1.15 mL | 5.76 mL | 11.51 mL |
| 5 mM | 0.23 mL | 1.15 mL | 2.3 mL |
| 10 mM | 0.12 mL | 0.58 mL | 1.15 mL |
| 50 mM | 0.02 mL | 0.12 mL | 0.23 mL |
| Formulation protocol: | 1. Liu S, Ge Y, Wang T, Edwards H, Ren Q, Jiang Y, Quan C, Wang G. Inhibition of ATR potentiates the cytotoxic effect of gemcitabine on pancreatic cancer cells through enhancement of DNA damage and abrogation of ribonucleotide reductase induction by gemcitabine. Oncol Rep. 2017 Jun;37(6):3377-3386. doi: 10.3892/or.2017.5580. Epub 2017 Apr 19. PMID: 28440428; PMCID: PMC6918818. 2. Ma J, Li X, Su Y, Zhao J, Luedtke DA, Epshteyn V, Edwards H, Wang G, Wang Z, Chu R, Taub JW, Lin H, Wang Y, Ge Y. Mechanisms responsible for the synergistic antileukemic interactions between ATR inhibition and cytarabine in acute myeloid leukemia cells. Sci Rep. 2017 Feb 8;7:41950. doi: 10.1038/srep41950. PMID: 28176818; PMCID: PMC5296912. 3. Foote KM, Blades K, Cronin A, Fillery S, Guichard SS, Hassall L, Hickson I, Jacq X, Jewsbury PJ, McGuire TM, Nissink JW, Odedra R, Page K, Perkins P, Suleman A, Tam K, Thommes P, Broadhurst R, Wood C. 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. doi: 10.1021/jm301859s. Epub 2013 Mar 1. PMID: 23394205. |
| In vitro protocol: | 1. Liu S, Ge Y, Wang T, Edwards H, Ren Q, Jiang Y, Quan C, Wang G. Inhibition of ATR potentiates the cytotoxic effect of gemcitabine on pancreatic cancer cells through enhancement of DNA damage and abrogation of ribonucleotide reductase induction by gemcitabine. Oncol Rep. 2017 Jun;37(6):3377-3386. doi: 10.3892/or.2017.5580. Epub 2017 Apr 19. PMID: 28440428; PMCID: PMC6918818. 2. Ma J, Li X, Su Y, Zhao J, Luedtke DA, Epshteyn V, Edwards H, Wang G, Wang Z, Chu R, Taub JW, Lin H, Wang Y, Ge Y. Mechanisms responsible for the synergistic antileukemic interactions between ATR inhibition and cytarabine in acute myeloid leukemia cells. Sci Rep. 2017 Feb 8;7:41950. doi: 10.1038/srep41950. PMID: 28176818; PMCID: PMC5296912. |
| In vivo protocol: | 1. Foote KM, Blades K, Cronin A, Fillery S, Guichard SS, Hassall L, Hickson I, Jacq X, Jewsbury PJ, McGuire TM, Nissink JW, Odedra R, Page K, Perkins P, Suleman A, Tam K, Thommes P, Broadhurst R, Wood C. 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. doi: 10.1021/jm301859s. Epub 2013 Mar 1. PMID: 23394205. |
1: Foote KM, Blades K, Cronin A, Fillery S, Guichard SS, Hassall L, Hickson I, Jacq X, Jewsbury PJ, McGuire TM, Nissink JW, Odedra R, Page K, Perkins P, Suleman A, Tam K, Thommes P, Broadhurst R, Wood C. 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. doi: 10.1021/jm301859s. Epub 2013 Mar 1. PubMed PMID: 23394205.
