Ceralasertib (AZD6738)

Catalog No.S7693 Batch:S769306

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Technical Data

Formula

C20H24N6O2S
Molecular Weight 412.51 CAS No. 1352226-88-0
Solubility (25°C)* In vitro DMSO 83 mg/mL (201.2 mM)
Ethanol 10 mg/mL (24.24 mM)
Water Insoluble
In vivo (Add solvents to the product individually and in order)
Homogeneous suspension
CMC-NA
≥5mg/ml Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

Biological Activity

Description Ceralasertib (AZD6738) is an orally active, and selective ATR kinase inhibitor with IC50 of 1 nM. Phase 1/2.
Targets
ATR [1]
(Cell-free assay)
1 nM
In vitro

In four Kras mutant cell lines: H23, H460, A549, and H358, AZD6738 inhibits ATR kinase activity and impairs cell viability. In ATM-deficient H23 cells, AZD6738 strongly synergizes with NSC 119875 to induce rapid cell death. [1] In p53 or ATM defective cells, AZD6738 treatment results in replication fork stalls and accumulation of unrepaired DNA damage, resulting in cell death by mitotic catastrophe. [2]
In vivo

In nude mice bearing H460 and H23 tumors, AZD6738 (50 mg/kg, p.o.) results in tumor growth inhibition (TGI), and the the combination with NSC 119875 causes rapid regression of ATM-deficient H23 tumors. [1] In nude mice bearing LoVo xenografts, a combination of AZD6738 (50 mg/kg) + IR (2 Gy) avoids toxicity while still maintaining efficacy. [3]

Protocol (from reference)

Cell Assay:

[1]
  • Cell lines

    H23, H460, A549, and H358 cells

  • Concentrations

    ~30 μM

  • Incubation Time

    48 h

  • Method

    Cells are treated in white walled, clear bottom 96-well plates with the indicated doses of AZD6738, NSC 119875, LY-188011, or combination for 48 h. ATP levels are assessed as surrogate measure of viability is assessed using the CellTiter-Glo Luminescent Cell Viability Assay and Safire2 plate reader. Raw data are corrected for background luminescence prior to further analysis. For AZD6738 treatment, log dose response curves are generated in GraphPad Prism 6 by nonlinear regression (log(inhibitor) vs. response with variable slope) of log-transformed (x = log(x)) data normalized to the mean of untreated controls. GI50 values, defined as the dose X at which Y = 50%, were extrapolated from dose response curves.
Animal Study:

[1]
  • Animal Models

    Female athymic nude mice bearing H23 or H460 xenografts

  • Dosages

    25 or 50 mg/kg

  • Administration

    p.o.

References

  • https://pubmed.ncbi.nlm.nih.gov/26517239/
  • https://pubmed.ncbi.nlm.nih.gov/26312880/
  • https://pubmed.ncbi.nlm.nih.gov/26310312/

Customer Product Validation

Number of γH2AX foci per cell of irradiated (2 Gy) SAS cells treated with inhibitors against ATM (ATMi, KU55933), DNA-PK (DNA-PKi, KU57788), or ATR (ATRi, AZD6738) with or without LY364947.

Data from [ , , Clin Cancer Res, 2018, doi:10.1158/1078-0432.CCR-18-1346 ]

Histograms showing the analysis results of RPMI8226 (transfection with control shRNA or HMGB1 shRNA) apoptosis induced by Dex (100 μM) in presence of AZD6738 (2 μM, an ATR inhibitor) (*P<0.05,**P<0.01,***P<0.001)

Data from [ , , J Exp Clin Cancer Res, 2018, 37(1):205 ]

AZD6738 (AZD) synergizes with cytarabine (ara-C) to induce apoptosis and proliferation inhibition in AML cells. (a) OCI-AML3 cells were treated with cytarabine and AZD6738, alone or in combination, for 24 h and then subjected to annexin V-FITC/PI staining and flow cytometry analyses. CI values were calculated using CompuSyn software. Combined drug treatments were compared to single drug treatment using 1-way ANOVA with Bonferroni post hoc test. ***indicates p < 0.001. (b and c) OCI-AML3 cells were treated with cytarabine and AZD-6738, alone or in combination, for 24 h. Whole cell lysates were subjected to Western blotting and probed with the indicated antibodies.

Data from [ , , Sci Rep, 2017, 7:41950 ]

MyLa2000 cells were irradiated with UVA at dose 1.6 J/cm2. Kinase inhibitors were added at the following concentrations: 10 μM VE-821, 1 μM VE-822, 1.6 μM Chir-124, 1 μM AZD6738, 1 μM MK8776 (selected basing on toxicity studies performed previously; data not shown) 30 minutes before irradiation (30 min before UVA), immediately before irradiation (0 min before UVA) or immediately after irradiation (0 min after UVA). Cell viability was analyzed 48 hours after treatment by PI exclusion assay.

Data from [ , , J Dermatol Sci, 2016, 84(3):239-247 ]

Selleck's Ceralasertib (AZD6738) Has Been Cited by 146 Publications

KEAP1 and STK11/LKB1 alterations enhance vulnerability to ATR inhibition in KRAS mutant non-small cell lung cancer [ Cancer Cell, 2025, 43(8):1530-1548.e9] PubMed: 40645185
Chromosome mis-segregation triggers cell cycle arrest through a mechanosensitive nuclear envelope checkpoint [ Nat Cell Biol, 2025, 27(1):73-86] PubMed: 39779939
WNK1-dependent water influx is required for CD4+ T cell activation and T cell-dependent antibody responses [ Nat Commun, 2025, 16(1):1857] PubMed: 39984435
KLF5 loss sensitizes cells to ATR inhibition and is synthetic lethal with ARID1A deficiency [ Nat Commun, 2025, 16(1):480] PubMed: 39779698
CHD6 has poly(ADP-ribose)- and DNA-binding domains and regulates PARP1/2-trapping inhibitor sensitivity via abasic site repair [ Nat Commun, 2025, 16(1):1026] PubMed: 39863586
The DNA replication checkpoint prevents PCNA/RFC depletion to protect forks from HLTF-induced collapse in human cells [ Mol Cell, 2025, 85(13):2474-2486.e6] PubMed: 40578346
USP37 counteracts HLTF to protect damaged replication forks and promote survival of BRCA1-deficient cells and PARP inhibitor resistance [ Nucleic Acids Res, 2025, 53(12)gkaf544] PubMed: 40548939
WIP1 mutations suppress DNA damage triggered bypass of the mitotic timer [ EMBO J, 2025, 10.1038/s44318-025-00495-0] PubMed: 40551011
Gemcitabine and ATR inhibitors synergize to kill PDAC cells by blocking DNA damage response [ Mol Syst Biol, 2025, 21(3):231-253] PubMed: 39838187
Halting hepatocellular carcinoma: Identifying intercellular crosstalk in HBV-driven disease [ Cell Rep, 2025, 44(4):115457] PubMed: 40163359

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

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