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Ceralasertib (AZD6738)

Catalog No.S7693 Purity: 99.64%

Ceralasertib (AZD6738) is an orally active, and selective ATR kinase inhibitor with IC50 of 1 nM. Phase 1/2.

Ceralasertib (AZD6738) Chemical Structure

CAS: 1352226-88-0

Selleck's Ceralasertib (AZD6738) has been cited by 104 publications

Purity & Quality Control

Batch: Purity: 99.64%

99.64

Products often used together with Ceralasertib (AZD6738)

Durvalumab (anti-PD-L1)

Ceralasertib and Durvalumab combination has promising antitumor activity, with durable responses in patients with refractory advanced gastric cancer (AGC).

Kwon M, et al. J Immunother Cancer. 2022 Jul;10(7):e005041.

Olaparib (AZD2281)

Ceralasertib and Olaparib combination is undergoing a phase II study for metastatic triple-negative breast cancer (TNBC).

Clark CA, et al. Front Oncol. 2021 Sep 24;11:703802.

Carboplatin

Ceralasertib and Carboplatin combination demonstrate excellent anticancer potential in phase I studies in cancer patients.

Huang X, et al. J Enzyme Inhib Med Chem. 2023 Dec;38(1):2237209.

Paclitaxel

Ceralasertib and Paclitaxel combination demonstrate excellent anticancer potential in phase I studies in cancer patients.

Huang X, et al. J Enzyme Inhib Med Chem. 2023 Dec;38(1):2237209.

Adavosertib (MK-1775)

Ceralasertib and Adavosertib combination exert more potent anti-tumor effects against biliary tract cancer.

Wang LW, et al. Molecules. 2022 Apr 12;27(8):2491.

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Cell Data

Cell Lines	Assay Type	Concentration	Incubation Time	Activity Description	PMID
LICR-LON-HN4 and LICR-LON-HN5 cells	Function assay	0.03, 0.1, 0.3, 1, 3, 10 μM		AZD6738 inhibition of ATR through loss of downstream phosphorylation of CHK1 on Ser345.	30057890
K8484 cells	Function assay	2 μM	7 hours	In K8484 cells, AZD6738 at 2 µM completely prevented gemcitabine-induced Chk1 phosphorylation on Serine 345, the downstream ATR target.	29891488
SNU-601 cells	Cell growth inhibition assay	0-1 μmol/L	5 days	The S and sub-G1 populations of SNU-601 cells were dramatically and dose-dependently increased by AZD6738.	28138034
breast cancer cell lines	Cell growth inhibition assay	0.125, 0.25, 0.5 and 1.0 μM	5 days	IC50 values ranged from 0.3 to >1 μmol/L	27501113
LoVo cells	Function assay		24 h	Reduction in cell count; a proportion of the cell population are (in addition to cell cycle arrest) undergoing apoptosis when exposed to drug at concentrations greater than 3 μM	26310312
HT29 cells	Function assay		60 mins	IC50 = 0.074 μM	30346772
LoVo cells	Cytotoxicity assay		72 hrs	GI50 = 0.44 μM	30346772
LoVo cells	Function assay	25 mg/kg	8 hrs	Cp = 0.74 μM	30346772
LoVo cells	Function assay	50 mg/kg	8 hrs	Cp = 2.2 μM	30346772
HT-29 cells	Cytotoxicity assay		72 hrs	GI50 = 2.6 μM	30346772
LoVo cells	Function assay	75 mg/kg	8 hrs	Cp = 2.6 μM	30346772
MDA-MB-468 cells	Function assay			IC50 = 5.7 μM	30346772
Click to View More Cell Line Experimental Data

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 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]
Cell Research	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.
Experimental Result Images	Methods	Biomarkers	Images	PMID
	Western blot	ATM pSer1981 / ATM / ATR / Chk1 pSer345 / Chk1 / Chk2 pThr68 / Chk2 pCHK1 / pCDC25c / pRPA32 / γH2AX / pHH3 / cleaved caspase-3 / RAD51		26563132
	Immunofluorescence	53BP1 γH2AX / RAD51		26563132
	Growth inhibition assay	IC50 Cell viability		28062704

In Vivo
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]
Animal Research	Animal Models	Female athymic nude mice bearing H23 or H460 xenografts
	Dosages	25 or 50 mg/kg
	Administration	p.o.

NCT Number	Recruitment	Conditions	Sponsor/Collaborators	Start Date	Phases
Clinical Trial Information (data from https://clinicaltrials.gov, updated on 2024-01-11)
NCT05941897	Recruiting	Advanced or Metastatic NSCLC	AstraZeneca	June 21 2023	Phase 2
NCT05514132	Active not recruiting	Advanced Solid Tumours	AstraZeneca	September 23 2022	Phase 1
NCT05450692	Recruiting	Advanced or Metastatic Non-Small Cell Lung Cancer	AstraZeneca\|Parexel	September 15 2022	Phase 3
NCT05061134	Active not recruiting	Melanoma	AstraZeneca	August 11 2022	Phase 2
NCT05469919	Active not recruiting	Advanced Solid Malignancies	AstraZeneca	June 9 2022	Phase 1
NCT04704661	Recruiting	Advanced Breast Carcinoma\|Advanced Colon Carcinoma\|Advanced Colorectal Carcinoma\|Advanced Endometrial Carcinoma\|Advanced Gastric Carcinoma\|Advanced Gastroesophageal Junction Adenocarcinoma\|Advanced Malignant Solid Neoplasm\|Advanced Salivary Gland Carcinoma\|Anatomic Stage III Breast Cancer AJCC v8\|Anatomic Stage IIIA Breast Cancer AJCC v8\|Anatomic Stage IIIB Breast Cancer AJCC v8\|Anatomic Stage IIIC Breast Cancer AJCC v8\|Anatomic Stage IV Breast Cancer AJCC v8\|Clinical Stage III Gastric Cancer AJCC v8\|Clinical Stage III Gastroesophageal Junction Adenocarcinoma AJCC v8\|Clinical Stage IV Gastric Cancer AJCC v8\|Clinical Stage IV Gastroesophageal Junction Adenocarcinoma AJCC v8\|Clinical Stage IVA Gastric Cancer AJCC v8\|Clinical Stage IVA Gastroesophageal Junction Adenocarcinoma AJCC v8\|Clinical Stage IVB Gastric Cancer AJCC v8\|Clinical Stage IVB Gastroesophageal Junction Adenocarcinoma AJCC v8\|HER2-Positive Breast Carcinoma\|Malignant Hepatobiliary Neoplasm\|Metastatic Breast Carcinoma\|Metastatic Gastroesophageal Junction Adenocarcinoma\|Metastatic Malignant Solid Neoplasm\|Pathologic Stage III Gastric Cancer AJCC v8\|Pathologic Stage III Gastroesophageal Junction Adenocarcinoma AJCC v8\|Pathologic Stage IIIA Gastric Cancer AJCC v8\|Pathologic Stage IIIA Gastroesophageal Junction Adenocarcinoma AJCC v8\|Pathologic Stage IIIB Gastric Cancer AJCC v8\|Pathologic Stage IIIB Gastroesophageal Junction Adenocarcinoma AJCC v8\|Pathologic Stage IIIC Gastric Cancer AJCC v8\|Pathologic Stage IV Gastric Cancer AJCC v8\|Pathologic Stage IV Gastroesophageal Junction Adenocarcinoma AJCC v8\|Pathologic Stage IVA Gastroesophageal Junction Adenocarcinoma AJCC v8\|Pathologic Stage IVB Gastroesophageal Junction Adenocarcinoma AJCC v8\|Prognostic Stage III Breast Cancer AJCC v8\|Prognostic Stage IIIA Breast Cancer AJCC v8\|Prognostic Stage IIIB Breast Cancer AJCC v8\|Prognostic Stage IIIC Breast Cancer AJCC v8\|Prognostic Stage IV Breast Cancer AJCC v8\|Stage III Colon Cancer AJCC v8\|Stage III Colorectal Cancer AJCC v8\|Stage III Major Salivary Gland Cancer AJCC v8\|Stage III Uterine Corpus Cancer AJCC v8\|Stage IIIA Colon Cancer AJCC v8\|Stage IIIA Colorectal Cancer AJCC v8\|Stage IIIA Uterine Corpus Cancer AJCC v8\|Stage IIIB Colon Cancer AJCC v8\|Stage IIIB Colorectal Cancer AJCC v8\|Stage IIIB Uterine Corpus Cancer AJCC v8\|Stage IIIC Colon Cancer AJCC v8\|Stage IIIC Colorectal Cancer AJCC v8\|Stage IIIC Uterine Corpus Cancer AJCC v8\|Stage IIIC1 Uterine Corpus Cancer AJCC v8\|Stage IIIC2 Uterine Corpus Cancer AJCC v8\|Stage IV Colon Cancer AJCC v8\|Stage IV Colorectal Cancer AJCC v8\|Stage IV Major Salivary Gland Cancer AJCC v8\|Stage IV Uterine Corpus Cancer AJCC v8\|Stage IVA Colon Cancer AJCC v8\|Stage IVA Colorectal Cancer AJCC v8\|Stage IVA Major Salivary Gland Cancer AJCC v8\|Stage IVA Uterine Corpus Cancer AJCC v8\|Stage IVB Colon Cancer AJCC v8\|Stage IVB Colorectal Cancer AJCC v8\|Stage IVB Major Salivary Gland Cancer AJCC v8\|Stage IVB Uterine Corpus Cancer AJCC v8\|Stage IVC Colon Cancer AJCC v8\|Stage IVC Colorectal Cancer AJCC v8\|Stage IVC Major Salivary Gland Cancer AJCC v8\|Unresectable Colorectal Carcinoma\|Unresectable Gastroesophageal Junction Adenocarcinoma\|Unresectable Malignant Solid Neoplasm	National Cancer Institute (NCI)	August 9 2021	Phase 1

References
[1] Vendetti FP, et al. Oncotarget. 2015. doi: 10.18632/oncotarget.6247. [2] Kwok M, et al. Lancet. 2015. doi: 10.1016/S0140-6736(15)60373-7. [3] Checkley S, et al. Sci Rep. 2015. doi: 10.1038/srep13545.

References

Chemical lnformation & Solubility

Molecular Weight	412.51	Formula	C₂₀H₂₄N₆O₂S
CAS No.	1352226-88-0	SDF	Download Ceralasertib (AZD6738) SDF
Smiles	CC1COCCN1C2=NC(=NC(=C2)C3(CC3)S(=N)(=O)C)C4=C5C=CNC5=NC=C4
Storage (From the date of receipt)	3 years-20°Cpowder	Storage of Stock Solutions Aliquot the stock solutions to avoid repeated freeze-thaw cycles	1 year-80°Cin solvent
Storage (From the date of receipt)	3 years-20°Cpowder		1 month-20°Cin solvent

In vitro
Batch:

DMSO : 83 mg/mL ( (201.2 mM)； Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Ethanol : 83 mg/mL

Water : Insoluble

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In vivo
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Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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