Ceralasertib (AZD6738)

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

Ceralasertib (AZD6738) Chemical Structure

Ceralasertib (AZD6738) Chemical Structure

CAS No. 1352226-88-0

Purity & Quality Control

Products often used together with Ceralasertib (AZD6738)

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Ceralasertib (AZD6738) Related Products

Signaling Pathway

Cell Data

Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
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
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
K8484 cells Function assay 2 μM 7 hours In K8484 cells, AZD6738 at 2 µM completely prevented LY-188011-induced Chk1 phosphorylation on Serine 345, the downstream ATR target. 29891488
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
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 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]

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, 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.

Experimental Result Images Methods Biomarkers Images PMID
Western blot pCHK1 / pCDC25c / pRPA32 / γH2AX / pHH3 / cleaved caspase-3 / RAD51 ATM pSer1981 / ATM / ATR / Chk1 pSer345 / Chk1 / Chk2 pThr68 / Chk2 29605721
Immunofluorescence γH2AX / RAD51 53BP1 29605721
Growth inhibition assay Cell viability IC50 26563132
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 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]

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
NCT05941897 Active not 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

Chemical Information & 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)

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.

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