Ceralasertib

Summary

Ceralasertib (CHEMBL4285417) is a phase-3 clinical-stage small molecule targeting ATR; indicated across 22 conditions including non-small cell lung carcinoma and neoplasm.

At a glance

• Status: Max clinical phase 3 (not approved)
• Modality: Small molecule
• Targets: 1 (ATR)
• Indications: 22 conditions
• Clinical trials: 46
• Chemistry: 412.5 Da · C20H24N6O2S

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL4285417
Name	Ceralasertib
Type	Small molecule
Max phase	3
FDA approved	no
PubChem CID	54761306
Molecular formula	C20H24N6O2S
Molecular weight	412.5
InChIKey	OHUHVTCQTUDPIJ-JYCIKRDWSA-N

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

IUPAC 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

Also known as: Atr kinase inhibitor azd6738, Azd 6738, Azd-6738, AZD6738, Ceralasertib, CERALASERTIB, US8552004, 2.02, AZD6737

Patent coverage: 614 distinct patent families (1,469 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 1,400 (95%) of the total. Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.

Targets

Targets

Primary targets (GtoPdb curated mechanism): the Cancer dependency column is the DepMap CRISPR fitness signal (% of screened cell lines dependent on the target).

Gene	Target	Action	pAffinity	Cancer dependency	UniProt
ATR	ATR checkpoint kinase	Inhibition	9		Q13535

Broader ChEMBL bioactivity targets: 5 (assay-derived). Sample: Serine/threonine-protein kinase mTOR, DNA-dependent protein kinase catalytic subunit, Transcription initiation factor TFIID subunit 1, ATR/ATRIP, Serine/threonine-protein kinase ATR.

Bioactivity

ChEMBL activities: 19 potent at pChembl ≥ 5 of 19 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
ATR	10.22	Ki	0.06	nM	CHEMBL_ACT_25850607
ATR	9	IC50	1	nM	CHEMBL_ACT_26005652
ATR	8.43	IC50	3.75	nM	CHEMBL_ACT_17610344
ATR	8.4	IC50	4	nM	CHEMBL_ACT_18779287
ATR	7.85	IC50	14	nM	CHEMBL_ACT_25850594
ATR	7.82	IC50	15	nM	CHEMBL_ACT_29164062
ATR	7.75	IC50	18	nM	CHEMBL_ACT_24896615
ATR	7.33	IC50	47	nM	CHEMBL_ACT_25850749
ATR	7.23	IC50	58.34	nM	CHEMBL_ACT_17610348
ATR	7.13	IC50	74	nM	CHEMBL_ACT_18779286
TAF1	6.76	Kd	175	nM	CHEMBL_ACT_24410247
ATR	6.75	IC50	180	nM	CHEMBL_ACT_25850611
MTOR	6.43	IC50	370	nM	CHEMBL_ACT_18779480
TAF1	6.37	Kd	427	nM	CHEMBL_ACT_24410250
TAF1	5.78	Kd	1670	nM	CHEMBL_ACT_24410242
TAF1	5.77	Kd	1690	nM	CHEMBL_ACT_24410238
MTOR	5.42	IC50	3800	nM	CHEMBL_ACT_25850588
MTOR	5.24	IC50	5700	nM	CHEMBL_ACT_18779490
PRKDC	5.13	IC50	7400	nM	CHEMBL_ACT_25850585

Target pathways

Aggregated over 1 target gene(s): ATR.

Top Reactome pathways

34 total, by targets touching each:

Pathway	Targets	Genes
Meiotic synapsis	1	ATR
Reproduction	1	ATR
Meiosis	1	ATR
Cell Cycle	1	ATR
Disease	1	ATR
Activation of ATR in response to replication stress	1	ATR
Generic Transcription Pathway	1	ATR
Cellular responses to stress	1	ATR
Regulation of HSF1-mediated heat shock response	1	ATR
Cellular response to heat stress	1	ATR
Transcriptional Regulation by TP53	1	ATR
Regulation of TP53 Activity	1	ATR
HDR through Single Strand Annealing (SSA)	1	ATR
HDR through Homologous Recombination (HRR)	1	ATR
DNA Double-Strand Break Repair	1	ATR
Homology Directed Repair	1	ATR
HDR through Homologous Recombination (HRR) or Single Strand Annealing (SSA)	1	ATR
Homologous DNA Pairing and Strand Exchange	1	ATR
Processing of DNA double-strand break ends	1	ATR
Presynaptic phase of homologous DNA pairing and strand exchange	1	ATR
Fanconi Anemia Pathway	1	ATR
TP53 Regulates Transcription of DNA Repair Genes	1	ATR
Regulation of TP53 Activity through Phosphorylation	1	ATR
G2/M DNA damage checkpoint	1	ATR
G2/M Checkpoints	1	ATR
Cell Cycle Checkpoints	1	ATR
RNA Polymerase II Transcription	1	ATR
DNA Repair	1	ATR
Gene expression (Transcription)	1	ATR
Cellular responses to stimuli	1	ATR

Dominant GO biological processes

GO term	Targets
DNA damage checkpoint signaling	1
telomere maintenance	1
nucleobase-containing compound metabolic process	1
DNA replication	1
DNA repair	1
double-strand break repair	1
DNA damage response	1
negative regulation of DNA replication	1
response to xenobiotic stimulus	1
response to mechanical stimulus	1
replication fork processing	1
positive regulation of telomere maintenance via telomerase	1
cellular response to UV	1
interstrand cross-link repair	1
positive regulation of DNA damage response, signal transduction by p53 class mediator	1

Indications & clinical

Indications

22 indications (0 at ChEMBL trial phase 4). Phase below is the highest clinical-trial phase recorded for this drug against each disease — not the molecule’s overall approval status (that is in the Summary).

Indication	Trial phase	MONDO	EFO
non-small cell lung carcinoma	3	MONDO:0005233	EFO:0003060
neoplasm	2	MONDO:0005070	EFO:0000616
head and neck squamous cell carcinoma	2	MONDO:0010150	EFO:0000181
breast carcinoma	2	MONDO:0004989	EFO:0000305
small cell lung carcinoma	2	MONDO:0008433	EFO:0000702
breast neoplasm	2	MONDO:0021100	EFO:0003869
adenocarcinoma	2	MONDO:0004970	EFO:0000228
squamous cell carcinoma	2	MONDO:0005096	EFO:0000707
bile duct neoplasm	2	MONDO:0021662	MONDO:0003059
ovarian cancer	2	MONDO:0008170	MONDO:0008170
osteosarcoma	2	MONDO:0009807	EFO:0000637
carcinoma	2	MONDO:0004993	EFO:0000313
melanoma	2	MONDO:0005105	EFO:0000756
triple-negative breast carcinoma	2	MONDO:0005494	EFO:0005537
cholangiocarcinoma	2	MONDO:0019087	EFO:0005221
B-cell chronic lymphocytic leukemia	1	MONDO:0004948	EFO:0000095
diffuse large B-cell lymphoma	1	MONDO:0018905	EFO:0000403
prolymphocytic leukemia	1	MONDO:0001023	MONDO:0001023
non-Hodgkin lymphoma	1	MONDO:0018908	EFO:0005952

3 further indication records had no mapped disease name (EFO/MeSH-only) or were duplicates, and are omitted.

Clinical trials

Total trials: 46.

Phase distribution

Phase	Trials
PHASE2	28
PHASE1	15
PHASE3	2
PHASE1/PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT05450692	PHASE3	ACTIVE_NOT_RECRUITING	A Phase III Study of Ceralasertib Plus Durvalumab Versus Docetaxel in Patients With Non Small Cell Lung Cancer (NSCLC) Whose Disease Progressed On or After Prior Anti PD (L)1 Therapy And Platinum Based Chemotherapy
NCT06732401	PHASE3	ACTIVE_NOT_RECRUITING	Testing the Addition of AZD6738 (Ceralasertib) to Immunotherapy to Increase Time Without Cancer for Patients With Non-Small Cell Lung Cancer
NCT02813135	PHASE1/PHASE2	RECRUITING	European Proof-of-Concept Therapeutic Stratification Trial of Molecular Anomalies in Relapsed or Refractory Tumors
NCT03334617	PHASE2	ACTIVE_NOT_RECRUITING	Phase II Umbrella Study of Novel Anti-cancer Agents in Participants With NSCLC Who Progressed on an Anti-PD-1/PD-L1 Containing Therapy
NCT03579316	PHASE2	ACTIVE_NOT_RECRUITING	Adavosertib With or Without Olaparib in Treating Patients With Recurrent Ovarian, Primary Peritoneal, or Fallopian Tube Cancer
NCT03682289	PHASE2	ACTIVE_NOT_RECRUITING	Ceralasertib (AZD6738) Alone and in Combination With Olaparib or Durvalumab in Patients With Solid Tumors
NCT03740893	PHASE2	RECRUITING	PHOENIX DDR/Anti-PD-L1 Trial: A Pre-surgical Window of Opportunity and Post-surgical Adjuvant Biomarker Study of DNA Damage Response Inhibition With or Without Anti-PD-L1 Immunotherapy in Patients With Neoadjuvant Treatment Resistant Residual Triple Negative Breast Cancer
NCT03787680	PHASE2	ACTIVE_NOT_RECRUITING	Targeting Resistant Prostate Cancer With ATR and PARP Inhibition (TRAP Trial)
NCT03833440	PHASE2	ACTIVE_NOT_RECRUITING	Precision Immuno-Oncology for Advanced Non-small Cell Lung Cancer Patients With PD-1 ICI Resistance
NCT03878095	PHASE2	ACTIVE_NOT_RECRUITING	Testing Olaparib and AZD6738 in IDH1 and IDH2 Mutant Tumors
NCT04065269	PHASE2	ACTIVE_NOT_RECRUITING	ATr Inhibitor in Combination With Olaparib/Durvalumab (MEDI4736) in Gynaecological Cancers With ARId1A Loss or no Loss
NCT04090567	PHASE2	RECRUITING	Olaparib With Cediranib or AZD6738 for the Treatment of Advanced or Metastatic Germline BRCA Mutated Breast Cancer
NCT04417062	PHASE2	ACTIVE_NOT_RECRUITING	Olaparib With Ceralasertib in Recurrent Osteosarcoma
NCT04699838	PHASE2	RECRUITING	Chemo-Immunotherapy Followed by Durvalumab and Ceralasertib in Treatment Naïve Patients With Extensive Stage Small Cell Lung Cancer
NCT05061134	PHASE2	ACTIVE_NOT_RECRUITING	A Study of Ceralasertib Monotherapy and Ceralasertib Plus Durvalumab in Patients With Melanoma and Resistance to PD-(L)1 Inhibition
NCT05582538	PHASE2	RECRUITING	Restoring Sensitivity To Immunotherapy In Advanced Triple Negative Breast Cancer Exploiting Ceralasertib Priming Followed By Combined Durvalumab/Nab-Paclitaxel
NCT05941897	PHASE2	ACTIVE_NOT_RECRUITING	A Study to Investigate Efficacy and Safety of Ceralasertib Plus Durvalumab in Participants Aged ≥ 18 Years With Advanced or Metastatic Non-small Cell Lung Cancer Whose Disease Progressed on or After Prior Anti-PD-(L)1 Therapy and Platinum-based Chemotherapy
NCT06680050	PHASE2	RECRUITING	Phase II Study of Radiotherapy Followed by Durvalumab and Ceralasertib in Stage III NSCLC Patients With Thoracic Relapses +/- Oligometastases After PACIFIC Regimen
NCT06769126	PHASE2	RECRUITING	Using Biomarker Tests to Select and Test New, Personalized Treatments for Extensive Stage Small Cell Lung Cancer, PRISM Study
NCT02576444	PHASE2	TERMINATED	OLAParib COmbinations
NCT02664935	PHASE2	COMPLETED	National Lung Matrix Trial: Multi-drug Phase II Trial in Non-Small Cell Lung Cancer
NCT02937818	PHASE2	COMPLETED	A Phase II, Study to Determine the Preliminary Efficacy of Novel Combinations of Treatment in Patients With Platinum Refractory Extensive-Stage Small-Cell Lung Cancer
NCT03182634	PHASE2	UNKNOWN	The UK Plasma Based Molecular Profiling of Advanced Breast Cancer to Inform Therapeutic CHoices (plasmaMATCH) Trial
NCT03428607	PHASE2	COMPLETED	Study of AZD6738 and Olaparib Combination Therapy in Relapsed Small Cell Lung Cancer Patients [SUKSES-N2]
NCT03462342	PHASE2	COMPLETED	Combination ATR and PARP Inhibitor (CAPRI) Trial With AZD6738 and Olaparib in Recurrent Ovarian Cancer
NCT03780608	PHASE2	UNKNOWN	This Study is a Phase II Study of AZD6738 in Combination With Durvalumab in Patients With Solid Tumor (Cohort A (N=30): GC Who Have Failed Secondary Chemotherapy Treatments Regimen; Cohort B (B=30): Melanoma Patients Who Have Failed to IO)
NCT03801369	PHASE2	TERMINATED	AMTEC IIT: Phase 2 Multiarm Study in TNBC
NCT04239014	PHASE2	WITHDRAWN	A Study to Evaluate the Effectiveness and Tolerability of a Second Maintenance Treatment in Participants With Ovarian Cancer, Who Have Previously Received Polyadenosine 5’Diphosphoribose [Poly (ADP Ribose)] Polymerase Inhibitor (PARPi) Treatment.
NCT04298008	PHASE2	UNKNOWN	AZD6738 Plus Durvalumab in Biliary Tract Cancer
NCT04298021	PHASE2	UNKNOWN	DDR-Umbrella Study of DDR Targeting Agents in Advanced Biliary Tract Cancer
NCT04564027	PHASE2	COMPLETED	A Study Investigating DNA-damage Response Agents in Molecularly Altered Advanced Cancer
NCT02264678	PHASE1	ACTIVE_NOT_RECRUITING	Ascending Doses of Ceralasertib in Combination With Chemotherapy and/or Novel Anti Cancer Agents
NCT03328273	PHASE1	ACTIVE_NOT_RECRUITING	A Study of AZD6738 and Acalabrutinib in Subjects With Relapsed or Refractory Chronic Lymphocytic Leukemia (CLL)
NCT03770429	PHASE1	ACTIVE_NOT_RECRUITING	AZD6738 for Patients With Progressive MDS or CMML
NCT04550104	PHASE1	RECRUITING	A Platform Study of Novel Agents in Combination With Radiotherapy in NSCLC
NCT04704661	PHASE1	ACTIVE_NOT_RECRUITING	Testing the Combination of Two Anti-cancer Drugs, DS-8201a and AZD6738, for The Treatment of Advanced Solid Tumors Expressing the HER2 Protein or Gene, The DASH Trial
NCT05514132	PHASE1	ACTIVE_NOT_RECRUITING	A Study to Evaluate the Safety and Pharmacokinetics of Ceralasertib in Combination With Durvalumab in Chinese Patients With Advanced Solid Tumours
NCT06754761	PHASE1	NOT_YET_RECRUITING	Human ADME Study of [14C]-Ceralasertib (AZD6738) and Absolute Bioavailability of Ceralasertib
NCT01955668	PHASE1	COMPLETED	AZD6738 First Time in Patient Multiple Ascending Dose Study
NCT02223923	PHASE1	UNKNOWN	Phase I Study to Assess Safety of AZD6738 Alone and in Combination With Radiotherapy in Patients With Solid Tumours

Clinical evidence (CIViC)

No CIViC predictive evidence (expected for non-precision-medicine drugs).

Pharmacology

Pharmacogenomics

No PharmGKB pharmacogenomic data curated for this drug.

Related molecules

Related molecules

Molecules sharing ≥1 of this drug’s curated primary targets, merged from two biobtree sources and ranked by shared-target count, then clinical phase: ChEMBL clinical-stage candidates (development phase ≥2) and PubChem drug-class bioactivity (approved / known drugs acting on the target). Deduplicated by drug name; the drug’s own salt forms are excluded. Note: for a drug with few primary targets a shared-target match can reflect off-target / promiscuous binding rather than the same therapeutic mechanism — the phase ordering surfaces bona-fide therapeutics first.

9 molecules share ≥1 primary target. Top 9 by shared-target count:

Molecule	Source	Status	Shared targets
DACTOLISIB	ChEMBL	Phase 3	ATR
BERZOSERTIB	ChEMBL	Phase 2	ATR
CAMONSERTIB	ChEMBL	Phase 2	ATR
TUVUSERTIB	ChEMBL	Phase 2	ATR
Binimetinib	PubChem	Approved	ATR
Cobimetinib	PubChem	Approved	ATR
Fedratinib	PubChem	Approved	ATR
Fostamatinib	PubChem	Approved	ATR
Idelalisib	PubChem	Approved	ATR