AZ20
featured

    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.


Chemical Structure

img
AZ20
CAS# 1233339-22-4

Theoretical Analysis

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

Price and Availability

Size Price Availability Quantity
10.0mg USD 90.0 Same Day
25.0mg USD 150.0 Same Day
50.0mg USD 250.0 Same Day
100.0mg USD 450.0 Same Day
200.0mg USD 850.0 Same Day
500.0mg USD 1850.0 Same Day
1.0g USD 2950.0 Same Day
2.0g USD 4650.0 2 Weeks
5.0g USD 7950.0 2 Weeks
Click to view more sizes and prices
Bulk inquiry

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/

Solubility Data

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

Preparing Stock Solutions

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.

Recalculate based on batch purity %
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.

Molarity Calculator

Calculate the mass, volume, or concentration required for a solution.
=
x
x
g/mol

*When preparing stock solutions always use the batch-specific molecular weight of the product found on the vial label and SDS / CoA (available online).

Reconstitution Calculator

The reconstitution calculator allows you to quickly calculate the volume of a reagent to reconstitute your vial. Simply enter the mass of reagent and the target concentration and the calculator will determine the rest.

=
÷

Dilution Calculator

Calculate the dilution required to prepare a stock solution.
x
=
x

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.

AZ20

10.0mg / USD 90.0


Additional Information