Ceralasertib (AZD6738)

Catalog No.S7693 Batch:S769309

Technical Data

Formula

C₂₀H₂₄N₆O₂S

Molecular Weight

412.51

CAS No.

1352226-88-0

Solubility (25°C)*

In vitro

DMSO

82 mg/mL (198.78 mM)

Ethanol

5 mg/mL (12.12 mM)

Water

Insoluble

In vivo (Add solvents to the product individually and in order)

Clear solution

5%DMSO 1 40%propylene glycol 2 55%ddH2O

10.0mg/ml

Taking the 1 mL working solution as an example, add 50 μL of 200 mg/ml clarified DMSO stock solution to 400 μL of propylene glycol, mix evenly to clarify it; then continue to add 550 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.

* <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 cisplatin 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 cisplatin 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, cisplatin, gemcitabine, 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.

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, cisplatin, gemcitabine, 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

Customer Product Validation

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

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

: Data from [Data independently produced by , , Sci Rep, 2017, 7:41950]

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

Selleck's Ceralasertib (AZD6738) has been cited by 106 publications

Functionally-instructed modifiers of response to ATR inhibition in experimental glioma [ J Exp Clin Cancer Res, 2024, 43(1):77]	PubMed: 38475864
MGMT function determines the differential response of ATR inhibitors with DNA-damaging agents in glioma stem cells for GBM therapy [ Neurooncol Adv, 2024, 6(1):vdad165]	PubMed: 38213834
C16orf72/HAPSTR1/TAPR1 functions with BRCA1/Senataxin to modulate replication-associated R-loops and confer resistance to PARP disruption [ Nat Commun, 2023, 14(1):5003]	PubMed: 37591890
"Proteotranscriptomic analysis of advanced colorectal cancer patient derived organoids for drug sensitivity prediction" [ J Exp Clin Cancer Res, 2023, 42(1):8]	PubMed: 36604765
Irreversible HER2 inhibitors overcome resistance to the RSL3 ferroptosis inducer in non-HER2 amplified luminal breast cancer [ Cell Death Dis, 2023, 14(8):532]	PubMed: 37596261
DNA damage response inhibitors enhance tumour treating fields -TTFields) potency in glioma stem-like cells [ Br J Cancer, 2023, 10.1038/s41416-023-02454-0]	PubMed: 37777579
Mitotic perturbation is a key mechanism of action of decitabine in myeloid tumor treatment [ Cell Rep, 2023, 42(9):113098]	PubMed: 37714156
ATR protects ongoing and newly assembled DNA replication forks through distinct mechanisms [ Cell Rep, 2023, 42(7):112792]	PubMed: 37454295
Effector memory T cells induce innate inflammation by triggering DNA damage and a non-canonical STING pathway in dendritic cells [ Cell Rep, 2023, S2211-1247(23)01192-0]	PubMed: 37794597
Immunogenic cell death after combined treatment with radiation and ATR inhibitors is dually regulated by apoptotic caspases [ Front Immunol, 2023, 14:1138920]	PubMed: 37346039

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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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