Live from Open Targets Platform, fetched 2026-11-11 15:37 UTC. Every row links to its source record.

ATR ATR checkpoint kinase

ENSG00000175054 · protein coding · Open Targets profile

Serine/threonine protein kinase which activates checkpoint signaling upon genotoxic stresses such as ionizing radiation (IR), ultraviolet light (UV), or DNA replication stalling, thereby acting as a DNA damage sensor (PubMed:10597277, PubMed:10608806, PubMed:10859164, PubMed:11721054, PubMed:12791985, PubMed:12814551, PubMed:14657349, PubMed:14729973, PubMed:14742437, PubMed:15210935, PubMed:15496423, PubMed:16260606, PubMed:21144835, PubMed:21777809, PubMed:23273981, PubMed:25083873, PubMed:27723717, PubMed:27723720, PubMed:30139873, PubMed:33848395, PubMed:37788673, PubMed:37832547, PubMed:9427750, PubMed:9636169). Recognizes the substrate consensus sequence [ST]-Q (PubMed:10597277, PubMed:10608806, PubMed:10859164, PubMed:11721054, PubMed:12791985, PubMed:12814551, PubMed:14657349, PubMed:14729973, PubMed:14742437, PubMed:15210935, PubMed:15496423, PubMed:16260606, PubMed:21144835, PubMed:23273981, PubMed:27723717, PubMed:27723720, PubMed:33848395, PubMed:9427750, PubMed:9636169). Phosphorylates BRCA1, CHEK1, MCM2, RAD17, RBBP8, RPA2, SMC1 and p53/TP53, which collectively inhibit DNA replication and mitosis and promote DNA repair, recombination and apoptosis (PubMed:11114888, PubMed:11418864, PubMed:11865061, PubMed:21777809, PubMed:23273981, PubMed:25083873, PubMed:9925639). Phosphorylates 'Ser-139' of histone variant H2AX at sites of DNA damage, thereby regulating DNA damage response mechanism (PubMed:11673449). Required for FANCD2 ubiquitination (PubMed:15314022). Critical for maintenance of fragile site stability and efficient regulation of centrosome duplication (PubMed:12526805). Acts as a regulator of the S-G2 transition by restricting the activity of CDK1 during S-phase to prevent premature entry into G2 (PubMed:30139873). Acts as a regulator of the nuclear envelope integrity in response to DNA damage and stress (PubMed:25083873, PubMed:37788673, PubMed:37832547). Acts as a mechanical stress sensor at the nuclear envelope: relocalizes to the nuclear envelope in response to mechanical stress and mediates a checkpoint via phosphorylation of CHEK1 (PubMed:25083873). Also promotes nuclear envelope rupture in response to DNA damage by mediating phosphorylation of LMNA at 'Ser-282', leading to lamin disassembly (PubMed:37832547). Involved in the inflammatory response to genome instability and double- stranded DNA breaks: acts by localizing to micronuclei arising from genome instability and catalyzing phosphorylation of LMNA at 'Ser-395', priming LMNA for subsequent phosphorylation by CDK1 and micronuclei envelope rupture (PubMed:37788673). The rupture of micronuclear envelope triggers the cGAS-STING pathway thereby activating the type I interferon response and innate immunity (PubMed:37788673). Positively regulates the restart of stalled replication forks following activation by the KHDC3L-OOEP scaffold complex (By similarity). {ECO:0000250|UniProtKB:Q9JKK8, ECO:0000269|PubMed:10597277, ECO:0000269|PubMed:10608806, ECO:0000269|PubMed:10859164, ECO:0000269|PubMed:11114888, ECO:0000269|PubMed:11418864, ECO:0000269|PubMed:11673449, ECO:0000269|PubMed:11721054, ECO:0000269|PubMed:11865061, ECO:0000269|PubMed:12526805, ECO:0000269|PubMed:12791985, ECO:0000269|PubMed:12814551, ECO:0000269|PubMed:14657349, ECO:0000269|PubMed:14729973, ECO:0000269|PubMed:14742437, ECO:0000269|PubMed:15210935, ECO:0000269|PubMed:15314022, ECO:0000269|PubMed:15496423, ECO:0000269|PubMed:16260606, ECO:0000269|PubMed:21144835, ECO:0000269|PubMed:21777809, ECO:0000269|PubMed:23273981, ECO:0000269|PubMed:25083873, ECO:0000269|PubMed:27723717, ECO:0000269|PubMed:27723720, ECO:0000269|PubMed:30139873, ECO:0000269|PubMed:33848395, ECO:0000269|PubMed:37788673, ECO:0000269|PubMed:37832547, ECO:0000269|PubMed:9427750, ECO:0000269|PubMed:9636169, ECO:0000269|PubMed:9925639}.

None of the 4 drugs recorded against ATR is approved yet; 1 reached Phase 3

Each band is a group of drugs. It runs from the kind of drug on the left to the furthest stage that drug has reached in any disease on the right. Thicker bands mean more drugs.

Approved bands are highlighted. Withdrawn means the drug was pulled from the market or from development. A combined phase counts as the later one (Phase 1/2 is shown as Phase 2). Hover a band for the drug names. Source: Open Targets Platform, fetched live.

In 14 of 15 cancers, the evidence for ATR comes mainly from mutations found in tumours

Each row is a cancer, strongest overall evidence first. The two dots show how strong the inherited (germline) and tumour-mutation (somatic) evidence is; the line between them is the gap.

Inherited (germline) variantsMutations in tumours (somatic)

Scores run from 0 (no evidence) to 1 (strongest). A missing dot at 0 means Open Targets holds no evidence of that kind. Source: Open Targets Platform, fetched live.

Tractability

Small molecule: Advanced Clinical, High-Quality Ligand, Druggable Family
PROTAC: Database Ubiquitination, Half-life Data, Small Molecule Binder

gnomAD loss of function constraint: o/e 0.46511000394821167 (upper bound 0.5346199870109558). Low values mean loss of function is poorly tolerated, a safety flag for inhibition.

Who runs trials of these drugs

Principal investigators and study chairs on 57 registry trials, updated in the last three years, of the most advanced drugs against ATR (ceralasertib, berzosertib), ranked by Phase 2+ trials. Live from ClinicalTrials.gov.

Anish Thomas
National Cancer Institute (NCI) · 3 of 3 trials Phase 2+
Ph1/Ph2NCT04826341 · A Phase I/II Study of Sacituzumab Govitecan Plus Berzosertib in Small Cell Lung Cancer, Extra-Pulmonary Small Cell Neuroendocrine Cancer and Homologous Recombination-Deficient Cancers Resistant to PARP Inhibitors brief
Ph1/Ph2NCT04802174 · Lurbinectedin With Berzosertib, an ATR Kinase Inhibitor in Small Cell Cancers and High-Grade Neuroendocrine Cancers brief
Ph1/Ph2NCT02487095 · Trial of Topotecan With VX-970 (M6620), an ATR Kinase Inhibitor, in Small Cell Cancers and Extrapulmonary Small Cell Cancers brief
Andrew Tutt
Guy's Hospital, Great Maze Pond, London. · 2 of 2 trials Phase 2+
Ph2NCT03330847 · To Assess Safety and Efficacy of Agents Targeting DNA Damage Repair With Olaparib Versus Olaparib Monotherapy.brief
Ph2NCT03740893 · 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 brief
Liza C Villaruz
University of Pittsburgh Cancer Institute LAO · 1 of 2 trials Phase 2+
Ph1NCT02595931 · M6620 and Irinotecan Hydrochloride in Treating Patients With Solid Tumors That Are Metastatic or Cannot Be Removed by Surgery brief
Ph1/Ph2NCT04216316 · Testing the Addition of an Anti-cancer Drug, Berzosertib (M6620, VX-970), to the Usual Treatments (Carboplatin and Gemcitabine) and to Pembrolizumab for Patients With Advanced Squamous Cell Non-small Cell Lung Cancer brief
Anne C Chiang
SWOG Cancer Research Network · 1 of 1 trials Phase 2+
Ph2NCT06769126 · Using Biomarker Tests to Select and Test New, Personalized Treatments for Extensive Stage Small Cell Lung Cancer, PRISM Study brief
Arun Rajan
National Cancer Institute LAO · 1 of 1 trials Phase 2+
Ph2NCT03896503 · Randomized Trial of Topotecan With M6620, an ATR Kinase Inhibitor, in Small Cell Lung Cancers and Small Cell Cancers Outside of the Lungs brief
Atish D Choudhury
Dana-Farber - Harvard Cancer Center LAO · 1 of 1 trials Phase 2+
Ph2NCT03517969 · M6620 and Carboplatin With or Without Docetaxel in Treating Patients With Metastatic Castration-Resistant Prostate Cancer brief
Banu Arun
M.D. Anderson Cancer Center · 1 of 1 trials Phase 2+
Ph2NCT04090567 · Olaparib With Cediranib or AZD6738 for the Treatment of Advanced or Metastatic Germline BRCA Mutated Breast Cancer brief
Birgit Geoerger
Gustave Roussy, Cancer Campus, Grand Paris · 1 of 1 trials Phase 2+
Ph1/Ph2NCT02813135 · European Proof-of-Concept Therapeutic Stratification Trial of Molecular Anomalies in Relapsed or Refractory Tumors brief
Dwight H Owen
ECOG-ACRIN Cancer Research Group · 1 of 1 trials Phase 2+
Ph3NCT06732401 · Testing the Addition of AZD6738 (Ceralasertib) to Immunotherapy to Increase Time Without Cancer for Patients With Non-Small Cell Lung Cancer brief
Fiona Simpkins
University of Pennsylvania · 1 of 1 trials Phase 2+
Ph2NCT03462342 · Combination ATR and PARP Inhibitor (CAPRI) Trial With AZD6738 and Olaparib in Recurrent Ovarian Cancer brief
Gary W Middleton
University of Birmingham · 1 of 1 trials Phase 2+
Ph2NCT02664935 · National Lung Matrix Trial: Multi-drug Phase II Trial in Non-Small Cell Lung Cancer brief
Haiyi Jiang
AstraZeneca · 1 of 1 trials Phase 2+
Ph2NCT02937818 · 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 brief
jean-olivier ARNAUD
Assistance Publique -hôpitaux de Marseille · 1 of 1 trials Phase 2+
Ph2NCT03833440 · Precision Immuno-Oncology for Advanced Non-small Cell Lung Cancer Patients With PD-1 ICI Resistance brief
John Heymach
M.D. Anderson Cancer Center · 1 of 1 trials Phase 2+
Ph2NCT03334617 · Phase II Umbrella Study of Novel Anti-cancer Agents in Participants With NSCLC Who Progressed on an Anti-PD-1/PD-L1 Containing Therapy brief
Jordan D Berlin
Yale University Cancer Center LAO · 1 of 1 trials Phase 2+
Ph2NCT03641313 · Berzosertib and Irinotecan in Treating Patients With Progressive, Metastatic, or Unresectable TP53 Mutant Gastric or Gastroesophageal Junction Cancer brief

28 of 57 trials of drugs against ATR have sites only in United States

Registry trials of ceralasertib, berzosertib updated in the last three years, counted by the country group of their listed sites. A trial with sites in several groups counts in each; 45 of 57 have all sites in one country.

Sites only in this groupSites here and elsewhere

Site counts are not patients per country, and trials registered only outside ClinicalTrials.gov are not covered. Where sites are is a fact about the record, not a judgement of its quality. Europe is the EU and EEA, the UK and Switzerland. Source: ClinicalTrials.gov, fetched live.

9 trials of drugs against ATR were stopped early

Terminated, withdrawn and suspended interventional trials of ceralasertib, berzosertib, elimusertib, M4344, newest update first, live from ClinicalTrials.gov. Each reason is quoted exactly as the registry gives it; we do not sort reasons into safety, efficacy or business. Dates are the last registry update. Showing the 9 most recent of 9.

Ph1NCT06754761 brief why it stopped
terminated · 2026-09-03 · AstraZeneca · AZD6738 / ceralasertib
“A decision, based solely on business strategy, was taken to terminate study D533BC00002 on 22 December 2025, as the clinical development programme for ceralasertib has been discontinued.”
Ph1NCT06929260 brief why it stopped
terminated · 2026-07-24 · AstraZeneca · Ceralasertib
“The study terminated because the clinical development programme for Ceralasertib has been discontinued.”
Ph1NCT04149145 brief why it stopped
withdrawn · 2026-06-05 · University of Alabama at Birmingham · M4344+Niraparib
“never opened”
Ph2NCT03801369 brief why it stopped
terminated · 2026-02-25 · Gordon Mills, MD, PhD · Ceralasertib
“loss of funding”
Ph1NCT04267939 brief why it stopped
terminated · 2023-12-21 · Bayer · Elimusertib (BAY1895344)
“There was no anticipated benefit of the experimental combination as tested over available standard therapies; therefore Sponsor has decided to terminate the investigation.”
Ph2NCT02576444 brief why it stopped
terminated · 2022-12-28 · Joseph Paul Eder · matched by the registry's drug synonyms
“The study was paused during COVID and without the ability to initiate the 4th arm in the study, the decision was to terminate the study in 2022.”
Ph1NCT05010096 brief why it stopped
withdrawn · 2022-05-27 · M.D. Anderson Cancer Center · Elimusertib
“No participants Enrolled”
Ph1/Ph2NCT04655183 brief why it stopped
withdrawn · 2021-06-30 · EMD Serono Research & Development Institute, Inc. · M4344
“Trial withdrawn based on portfolio prioritization; oral ATRi M1774 in combination with niraparib is under investigation in DDRiver Solid Tumor 301”
Ph2NCT04239014 brief why it stopped
withdrawn · 2021-03-10 · AstraZeneca · Ceralasertib
“Sponsor made the decision to terminate the DUETTE study based on the interim analysis of the VIOLETTE study (NCT03330847) investigating the combination of ceralasertib and Olaparib, where study closure was recommended due to insufficient efficacy.”

Paediatric incentives and obligations for ATR's drugs

For ceralasertib, berzosertib, elimusertib, M4344: what EMA and FDA publish about paediatric plans, orphan status and pediatric approvals, and how many registered studies take children. Each line is a yes, no or not published fact from the record linked under it; none of it is a forecast.

FDA pediatric target list: yes · ATR is on the list. Membership alone neither requires nor waives a pediatric study.
Rule: Target is on FDA's Pediatric Molecular Target List (relevant targets). Source: FDA Pediatric Molecular Target List (Listed as February 2026 on the FDA Pediatric Oncology page; the file served is 9.7.22_the_relevant_molecular_target_list.xlsx, whose Summary of Changes sheet is headed 'SEPTEMBER 2022 UPDATE' (footnote date 2022-09-01)), 2026-11-11
EU paediatric investigation plan: yes · EMEA-003127-PIP01-21 (ceralasertib, Treatment of lung carcinoma (small cell and non-small cell carcinoma)): W: decision granting a waiver in all age groups for all conditions or indications, 11 Mar 2022
Rule: An EMA PIP decision (agreement, modification or waiver) lists the drug as its active substance, exact name. Source: EMA EMEA-003127-PIP01-21, 2026-11-11
EU orphan designation: yes · EU/3/22/2655 withdrawn 18 Jul 2022: Treatment of small cell lung cancer
Rule: An EU orphan designation lists the drug as its active substance (exact name) or belongs to a medicine that does; withdrawn and expired designations are listed with their status. Source: EMA EU/3/22/2655, 2026-11-11
Authorised in the EU: no · EMA lists no centrally authorised medicine of ceralasertib, berzosertib, elimusertib, m4344
Rule: An EMA medicine record lists the drug as its active substance or INN, exact name; national-only authorisations are not in this file. Source: EMA data download (dated snapshot), 2026-11-11
FDA orphan designation: not published · FDA's orphan designation database turns away automated requests, so this app does not read it; search it by hand at the link
Rule: Would be: an FDA orphan designation names the drug. Source: FDA orphan designations search
FDA pediatric oncology approval: no · FDA's table lists no pediatric approval of ceralasertib, berzosertib, elimusertib, m4344
Rule: FDA's Pediatric Oncology Drug Approvals table names the drug. Source: FDA Pediatric Oncology Drug Approvals (content current as of 2026-03-03), 2026-11-11
Registered studies open to children: yes · 6 interventional studies of ceralasertib, berzosertib, elimusertib, m4344 include patients under 18; 3 are recruiting, not yet recruiting or active
Rule: The registry's age group includes Child (birth to 17 years), which also counts studies that set no minimum age. Source: ClinicalTrials.gov search, 2026-11-11

Rare pediatric disease voucher. FDA, content current as of 29 Apr 2026: “As of February 3, 2026, enactment of the Consolidated Appropriations Act, 2026, the rare pediatric disease PRV program will sunset after September 30, 2029. FDA may not award any PRVs under this program after September 30, 2029.” Voucher sale prices are not shown here; they appear only as company-reported news. FDA: Rare Pediatric Disease Designation and Priority Review Voucher Programs

All 4 drugs and clinical candidates as a table

Each drug, stage and indication links to its Open Targets record, where the trials and approvals behind it are listed. Salt forms (for example a mesylate) are listed as Open Targets records them, as separate entries.

Drug	Type	Highest stage	Indications	Source records
CERALASERTIB	Small molecule	phase 3	non-small cell lung carcinoma, small cell lung carcinoma, ovarian cancer, endometrial cancer, malignant pancreatic neoplasm, pancreatic neoplasm, renal cell carcinoma, urothelial carcinoma, +21 more	Open Targets · ChEMBL
BERZOSERTIB	Small molecule	phase 2	fallopian tube cancer, primary peritoneal carcinoma, ovarian cancer, prostate cancer, gastric cancer, neoplasm, small cell carcinoma, small cell lung carcinoma, +5 more	Open Targets · ChEMBL
ELIMUSERTIB	Small molecule	phase 1 2	Ewing sarcoma, alveolar rhabdomyosarcoma, lymphoma, ovarian cancer, urothelial carcinoma, small cell lung carcinoma, pancreatic adenocarcinoma, gastric cancer, +4 more	Open Targets · ChEMBL
M4344	Small molecule	phase 1 2	breast cancer, neoplasm, ovarian cancer	Open Targets · ChEMBL