Ceralasertib (AZD-6738)

Alias: AZD6738; AZD-6738; AZD 6738

Cat No.:V0233 Purity: ≥98%

COA Product Data Instructions for use SDS

Ceralasertib (AZD-6738) Chemical Structure CAS No.: 1352226-88-0
Product category: ATM(ATR)

This product is for research use only, not for human use. We do not sell to patients.

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Citations by Top Journals: Nature, Cell, Science, etc.

Top Publications Citing lnvivochem Products

Nature 2021, 597(7874):119-125.

Cell 2020,183:1202-1218.e25.

Science Adv 2022: 8, eabm9427.

Nature 597, 119–125 (2021)

Cell Stem Cell 2020,26(6):845-861.e12.

Science Trans Med 2023,15(701):eadd7872.

STTT 2023,8(1):91.

Cell Reports 2023,42(4):112313

Science Trans Med 2023, 15: eadd7872.

Cancer Cell 2021,39(4):529-547.e7.

Cancer Discov 2022,12(4):1106-1127.

Immunity 2023,56(3):620-634.e11.

J Am Chem Soc 2022,144:21831-21836.

Cell 2020,183:1202-1218.e25.

Science Adv 2022:8,eabm9427.

Nature 2021,597(7874):119-125.

Cell 2020,183:1202-1218.e25.

PNAS Nexus 2022,1(3):pgac063.

ACS Nano 2023,17(10):9110-9125.

Biomaterial 2023 Sep16:302:122333.

Purity & Quality Control Documentation

Current batch：

Purity: ≥98%

COA

MSDS

NMR

Instructions

Product Description
Bioactivity & Protocols
Physicochemical Properties
Solubility Data
Calculators
Clinical Trial Information
Biological Data

Product Description

Ceralasertib (formerly AZD6738), a morpholino-pyrimidine-based DNA damage repair agent, is a potent, orally bioavailable and selective inhibitor of ATR (ataxia telangiectasia and rad3 related) kinase with potential antitumor activity. Its IC50 for ATR inhibition is 1 nM. The serine/threonine protein kinase ATR is upregulated in a number of different types of cancer cells. Phase I clinical trials are presently investigating it as a potential cancer treatment.

Biological Activity I Assay Protocols (From Reference)

Targets

ATR ( IC50 = 1 nM ); PI3Kδ ( IC50 = 6.8 μM ); DYRK ( IC50 = 10.8 μM )

ln Vitro

Ceralasertib (AZD6738) is a potent inhibitor of ATR kinase activity, with an IC50 of 0.001 μM against the isolated enzyme and 0.074 μM against the phosphorylation of CHK1 in cells that is dependent on ATR kinase. In non-small cell lung cancer (NSCLC) cell lines, celeralasertib (AZD6738) causes senescence and cell death. Four Kras mutant cell lines are less viable when ceralasertib (AZD6738) is used; H23, H460, A549, and H358 have the lowest GI50 and the largest maximal inhibition (1.05 μM, 88.0% and 2.38 μM, 86.2%, respectively). In NSCLC cell lines with intact ATM kinase signaling, ceralasertib (AZD6738) amplifies the cytotoxicity of CDDP and NSC 613327, and in ATM-deficient NSCLC cells, it potently synergizes with CDDP[1]. With IC50 values less than 1 μM, ceralasertib (AZD6738) inhibits human breast cancer cell lines using the MTT assay. Ceralasertib (AZD6738) causes apoptosis and cell cycle arrest. It suppresses cell proliferative signaling molecules and DNA damage response molecules[2].

ln Vivo

Ceralasertib (AZD6738) and ATR kinase inhibition given daily for 14 days in a row improves CDDP's therapeutic efficacy in xenograft models and is well tolerated by mice. It's amazing how well CDDP and Ceralasertib (AZD6738) work together to treat ATM-deficient lung cancer xenografts[1].

Enzyme Assay

AZD6738 is a potent inhibitor of ATR kinase activity, with an IC50 of 0.001 μM against the isolated enzyme and 0.074 μM against the phosphorylation of CHK1 in cells that is dependent on ATR kinase.

Cell Assay

Ceralasertib (AZD6738) is diluted in DMSO to the appropriate working concentrations after being dissolved at a 30 mM concentration. For Ceralasertib (AZD6738) dose response experiments, the final DMSO concentration in media for all conditions and controls is 0.1%; for Ceralasertib (AZD6738) + chemotherapy viability experiments, it is 0.05%; and for all experiments involving 0.3 μM and 1.0 μM doses of Ceralasertib (AZD6738), it is 0.025%[1].

Animal Protocol

Mice: Ceralasertib (AZD6738) is diluted 1:5 in propylene glycol after being dissolved in DMSO at a concentration of 25 mg/mL or 50 mg/mL. Ceralasertib (AZD6738) is given orally as a gavage for 14 days at a dose of 25 mg/kg (H23) or 50 mg/kg (H460). 10 mL/kg is the dosage volume.[1].

References

[1]. The orally active and bioavailable ATR kinase inhibitor AZD6738 potentiates the anti-tumor effects of CDDP to resolve ATM-deficient non-small cell lung cancer in vivo.

[2]. Anti-tumor activity of the ATR inhibitor AZD6738 in HER2 positive breast cancer cells. Int J Cancer. 2017 Jan 1;140(1):109-119.

These protocols are for reference only. InvivoChem does not independently validate these methods.

Physicochemical Properties

Molecular Formula

C20H24N6O2S

Molecular Weight

412.51

Exact Mass

412.17

Elemental Analysis

C, 58.23; H, 5.86; N, 20.37; O, 7.76; S, 7.77

CAS #

1352226-88-0

Related CAS #

1352226-88-0

Appearance

White solid powder

SMILES

C[C@@H]1COCCN1C2=NC(=NC(=C2)C3(CC3)[S@](=N)(=O)C)C4=C5C=CNC5=NC=C4

InChi Key

OHUHVTCQTUDPIJ-JYCIKRDWSA-N

InChi Code

InChI=1S/C20H24N6O2S/c1-13-12-28-10-9-26(13)17-11-16(20(5-6-20)29(2,21)27)24-19(25-17)15-4-8-23-18-14(15)3-7-22-18/h3-4,7-8,11,13,21H,5-6,9-10,12H2,1-2H3,(H,22,23)/t13-,29-/m1/s1

Chemical Name

imino-methyl-[1-[6-[(3R)-3-methylmorpholin-4-yl]-2-(1H-pyrrolo[2,3-b]pyridin-4-yl)pyrimidin-4-yl]cyclopropyl]-oxo-lambda6-sulfane

Synonyms

AZD6738; AZD-6738; AZD 6738

HS Tariff Code

2934.99.9001

Storage

Powder -20°C 3 years

4°C 2 years

In solvent -80°C 6 months

-20°C 1 month

Shipping Condition

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Solubility Data

Solubility (In Vitro)

DMSO: 82~125 mg/mL (198.7~303.0 mM)

Water: <1 mg/mL

Ethanol: ~41 mg/mL warmed (~99.4 mM)

Solubility (In Vivo)

10% DMSO+40% propylene glycol+ddH2O: 10mg/mL

(Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.4242 mL	12.1209 mL	24.2418 mL
	5 mM	0.4848 mL	2.4242 mL	4.8484 mL
	10 mM	0.2424 mL	1.2121 mL	2.4242 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.

Calculator

Mass

Concentration

Volume

Molecular Weight*

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Molarity Calculator allows you to calculate the mass, volume, and/or concentration required for a solution, as detailed below:

Calculate the Mass of a compound required to prepare a solution of known volume and concentration
Calculate the Volume of solution required to dissolve a compound of known mass to a desired concentration
Calculate the Concentration of a solution resulting from a known mass of compound in a specific volume

See Example

An example of molarity calculation using the molarity calculator is shown below:
What is the mass of compound required to make a 10 mM stock solution in 5 ml of DMSO given that the molecular weight of the compound is 350.26 g/mol?

Enter 350.26 in the Molecular Weight (MW) box
Enter 10 in the Concentration box and choose the correct unit (mM)
Enter 5 in the Volume box and choose the correct unit (mL)
Click the “Calculate” button
The answer of 17.513 mg appears in the Mass box. In a similar way, you may calculate the volume and concentration.

Concentration (Start)

Volume (Start)

Concentration (End)

Volume (End)

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Dilution Calculator allows you to calculate how to dilute a stock solution of known concentrations. For example, you may Enter C1, C2 & V2 to calculate V1, as detailed below:

What volume of a given 10 mM stock solution is required to make 25 ml of a 25 μM solution?
Using the equation C1V1 = C2V2, where C1=10 mM, C2=25 μM, V2=25 ml and V1 is the unknown:

Enter 10 into the Concentration (Start) box and choose the correct unit (mM)
Enter 25 into the Concentration (End) box and select the correct unit (mM)
Enter 25 into the Volume (End) box and choose the correct unit (mL)
Click the “Calculate” button
The answer of 62.5 μL (0.1 ml) appears in the Volume (Start) box

Molecular formula

Total molecular weight

g/mol

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Molecular Weight Calculator allows you to calculate the molar mass and elemental composition of a compound, as detailed below:

Note: Chemical formula is case sensitive: C12H18N3O4 c12h18n3o4
Instructions to calculate molar mass (molecular weight) of a chemical compound:

To calculate molar mass of a chemical compound, please enter the chemical/molecular formula and click the “Calculate’ button.

Definitions of molecular mass, molecular weight, molar mass and molar weight:

Molecular mass (or molecular weight) is the mass of one molecule of a substance and is expressed in the unified atomic mass units (u). (1 u is equal to 1/12 the mass of one atom of carbon-12)
Molar mass (molar weight) is the mass of one mole of a substance and is expressed in g/mol.

Volume (to add to vial)

Mass (in vial)

Desired Reconstitution Concentration

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Reconstitution Calculator allows you to calculate the volume of solvent required to reconstitute your vial.

Enter the mass of the reagent and the desired reconstitution concentration as well as the correct units
Click the “Calculate” button
The answer appears in the Volume (to add to vial) box

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal to make allowance for loss during the experiment)

Dosage mg/kg

Average weight of animals g

Dosing volume per animal μL

Number of animals

Step 2: Enter in vivo formulation (This is only a calculator, not the exact formulation for a specific product. Please contact us first if there is no in vivo formulation in the solubility section.)

% DMSO

% Tween 80

% ddH₂O

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Calculation results

Working concentration： mg/mL；

Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.

Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH₂O，mix and clarify.

Note： (1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.

Clinical Trial Information

NCT Number	Recruitment	interventions	Conditions	Sponsor/Collaborators	Start Date	Phases
NCT04564027	Active Recruiting	Drug: Ceralasertib	Advanced Solid Tumours	AstraZeneca	December 1, 2020	Phase 2
NCT03328273	Active Recruiting	Drug: Ceralasertib Drug: Acalabrutinib	Chronic Lymphocytic Leukemia	Acerta Pharma BV	January 31, 2018	Phase 1
NCT05061134	Active Recruiting	Drug: Ceralasertib Biological: Durvalumab	Melanoma	AstraZeneca	August 11, 2022	Phase 2
NCT05469919	Active Recruiting	Drug: Ceralasertib	Advanced Solid Malignancies	AstraZeneca	June 9, 2022	Phase 1
NCT05514132	Active Recruiting	Drug: Ceralasertib Drug: Durvalumab	Advanced Solid Tumours	AstraZeneca	September 23, 2022	Phase 1

Biological Data

Inhibition of ATR by AZD6738 inhibits growth of NSCLC cells and induces a DNA damage response.Oncotarget.2015 Dec 29;6(42):44289-305.
AZD6738 sensitizes NSCLC cell lines to cisplatin and synergizes strongly with cisplatin in ATM-deficient H23 cells.Oncotarget.2015 Dec 29;6(42):44289-305.
The combination of AZD6738 and cisplatin causes accumulation of cells in early S-phase and at the G1/S border.Oncotarget.2015 Dec 29;6(42):44289-305.
The combination of AZD6738 and cisplatin causes dramatic cell death of ATM-deficient cells independent of the ATM-p53 signaling pathway.Oncotarget.2015 Dec 29;6(42):44289-305.
AZD6738 sensitizes ATM knockdown cells to cisplatin.Oncotarget.2015 Dec 29;6(42):44289-305.
AZD6738 potentiates cisplatin efficacy in NSCLC xenografts, and the combination causes rapid regression of ATM-deficient H23 tumors.Oncotarget.2015 Dec 29;6(42):44289-305.