ATR

Summary

ATR (ATR checkpoint kinase, HGNC:882) is a protein-coding gene on chromosome 3q23, encoding Serine/threonine-protein kinase ATR (Q13535). 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.

The protein encoded by this gene is a serine/threonine kinase and DNA damage sensor, activating cell cycle checkpoint signaling upon DNA stress. The encoded protein can phosphorylate and activate several proteins involved in the inhibition of DNA replication and mitosis, and can promote DNA repair, recombination, and apoptosis. This protein is also important for fragile site stability and centrosome duplication. Defects in this gene are a cause of Seckel syndrome 1.

Source: NCBI Gene 545 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Seckel syndrome 1 (Definitive, GenCC) — +4 more curated relationships
• Clinical variants (ClinVar): 4,188 total — 96 pathogenic, 44 likely-pathogenic
• Phenotypes (HPO): 1
• Druggable target: yes — 8 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001184

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:882
Approved symbol	ATR
Name	ATR checkpoint kinase
Location	3q23
Locus type	gene with protein product
Status	Approved
Aliases	FRP1, SCKL, SCKL1, MEC1
Ensembl gene	ENSG00000175054
Ensembl biotype	protein_coding
OMIM	601215
Entrez	545

Gene structure

Transcript identifiers

Ensembl transcripts: 25 — 15 retained_intron, 5 protein_coding, 4 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000350721, ENST00000507148, ENST00000507620, ENST00000511016, ENST00000513291, ENST00000514393, ENST00000515149, ENST00000515810, ENST00000515863, ENST00000653868, ENST00000653893, ENST00000654170, ENST00000656114, ENST00000656582, ENST00000656590, ENST00000657914, ENST00000658083, ENST00000659195, ENST00000661310, ENST00000665483, ENST00000666447, ENST00000666943, ENST00000892891, ENST00000936442, ENST00000936443

RefSeq mRNA: 2 — MANE Select: NM_001184 NM_001184, NM_001354579

CCDS: CCDS3124, CCDS93402

Canonical transcript exons

ENST00000350721 — 47 exons

Exon	Start	End
ENSE00001205280	142496361	142496520
ENSE00001205292	142458958	142459111
ENSE00001205296	142459227	142459383
ENSE00001205300	142461940	142462090
ENSE00001205303	142465097	142465240
ENSE00001205308	142466324	142466533
ENSE00001205312	142467934	142468068
ENSE00001205316	142469337	142469569
ENSE00001205322	142470086	142470183
ENSE00001229183	142457604	142457755
ENSE00001229256	142493132	142493311
ENSE00001229291	142499627	142499718
ENSE00001229298	142503362	142503453
ENSE00001229310	142505139	142505303
ENSE00001229320	142507931	142508109
ENSE00001229328	142512260	142512470
ENSE00001229336	142513501	142513638
ENSE00001229346	142515395	142515515
ENSE00001229354	142519669	142519784
ENSE00001229360	142522728	142522841
ENSE00001229365	142523993	142524199
ENSE00001229371	142535080	142535205
ENSE00001229377	142536108	142536201
ENSE00001229380	142538482	142538625
ENSE00001229387	142540904	142541034
ENSE00001229397	142542665	142542757
ENSE00001229405	142547725	142547910
ENSE00001229413	142549479	142549673
ENSE00001229418	142550132	142550302
ENSE00001229428	142553227	142553398
ENSE00001229432	142553640	142553740
ENSE00001229438	142553825	142554015
ENSE00001229447	142555877	142556139
ENSE00001229459	142558624	142558776
ENSE00001229465	142559251	142559441
ENSE00001229471	142560263	142560454
ENSE00001229477	142562232	142563109
ENSE00001229482	142566121	142566261
ENSE00001229531	142568063	142568154
ENSE00001369208	142578646	142578733
ENSE00001416709	142485140	142485282
ENSE00003496871	142453128	142453233
ENSE00003515923	142449235	142449602
ENSE00003591356	142498597	142498774
ENSE00003609500	142561243	142561421
ENSE00003609638	142497013	142497192
ENSE00003785032	142556383	142556575

Expression profiles

Bgee: expression breadth ubiquitous, 289 present calls, max score 95.65.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 13.4913 / max 108.7795, expressed in 1780 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
44854	13.4833	1780
44853	0.0081	4

Top tissues by expression

295 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
Brodmann (1909) area 23	UBERON:0013554	95.65	gold quality
epithelium of nasopharynx	UBERON:0001951	94.49	gold quality
adrenal tissue	UBERON:0018303	93.26	gold quality
endothelial cell	CL:0000115	93.14	gold quality
caput epididymis	UBERON:0004358	92.29	gold quality
tibia	UBERON:0000979	92.25	gold quality
choroid plexus epithelium	UBERON:0003911	92.21	gold quality
corpus epididymis	UBERON:0004359	91.88	gold quality
germinal epithelium of ovary	UBERON:0001304	91.54	gold quality
middle temporal gyrus	UBERON:0002771	91.52	gold quality
bronchial epithelial cell	CL:0002328	91.29	gold quality
skin of hip	UBERON:0001554	91.10	gold quality
visceral pleura	UBERON:0002401	90.97	gold quality
gingival epithelium	UBERON:0001949	90.87	gold quality
cauda epididymis	UBERON:0004360	90.78	gold quality
parietal pleura	UBERON:0002400	90.72	gold quality
right adrenal gland cortex	UBERON:0035827	90.59	gold quality
adrenal cortex	UBERON:0001235	90.48	gold quality
left adrenal gland cortex	UBERON:0035825	90.33	gold quality
pleura	UBERON:0000977	90.27	gold quality
right adrenal gland	UBERON:0001233	90.11	gold quality
adrenal gland	UBERON:0002369	90.06	gold quality
left adrenal gland	UBERON:0001234	89.95	gold quality
primary visual cortex	UBERON:0002436	89.62	gold quality
granulocyte	CL:0000094	89.25	gold quality
tonsil	UBERON:0002372	89.03	gold quality
cervix squamous epithelium	UBERON:0006922	88.86	gold quality
sperm	CL:0000019	88.82	gold quality
epithelium of bronchus	UBERON:0002031	88.80	gold quality
pigmented layer of retina	UBERON:0001782	88.78	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

18 targeting ATR, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-4760-5P	99.80	69.88	1619
HSA-MIR-586	99.65	70.40	2051
HSA-MIR-5700	99.64	69.88	2280
HSA-MIR-8061	99.63	69.44	1411
HSA-MIR-4756-3P	99.62	66.30	1319
HSA-MIR-4251	99.40	69.19	3363
HSA-MIR-7160-5P	99.11	67.17	2207
HSA-MIR-140-3P	99.04	67.69	1324
HSA-MIR-10B-3P	99.04	66.98	988
HSA-MIR-4477A	98.83	69.75	2952
HSA-MIR-3613-5P	98.40	68.91	604
HSA-MIR-628-5P	98.36	67.74	844
HSA-MIR-383-5P	96.86	67.55	820

Literature-anchored findings (GeneRIF, showing 40)

• binds novel protein called ATRIP (ATR-interacting protein); ATRIP and ATR are mutually dependent partners in cell cycle checkpoint signaling pathways (PMID:11721054)
• ATR kinase plays an important role during tumor development in responding to hypoxia-induced replication arrest, and hypoxic conditions could select for the loss of key components of ATR-dependent checkpoint controls (PMID:11865061)
• lack of role in cellular response to DNA strand-scission enediyne C-1027 (PMID:11927575)
• ATR may function as an initial sensor in the DNA damage checkpoint response to UV. (PMID:12011431)
• ATR has a role in regulating cyclin B1 phosphorylation by inhibiting Plk1 kinase activity (PMID:12147700)
• Data suggest that the UVC-induced S checkpoint response of inhibition of replicon initiation is mediated by ATR signaling through Chk-1 and is independent of ATM, Nbs1, and Mre11. (PMID:12446774)
• ATR kinase has a critical role in the response of hypoxia and reperfusion in solid tumors. (PMID:12519769)
• ATR has a role in regulating chromosomal fragile sites and DNA replication (PMID:12526805)
• WRN and ATR colocalize after replication fork arrest, suggesting that WRN and the ATR kinase collaborate to prevent genome instability during the S phase. (PMID:12629512)
• activity of the ATR kinase is required for successful completion of the viral DNA integration process and/or survival of transduced cells (PMID:12679521)
• ATR has a role in the DNA damage-signaling pathway by a viral gene product (PMID:12738771)
• BRCA1 facilitates the ability of ATM and ATR to phosphorylate downstream substrates that directly influence cell cycle checkpoint arrest and apoptosis (PMID:12773400)
• the G2 checkpoint in irradiated human cells derives from an overactivation of the ATR/CHK1 pathway. (PMID:12791699)
• data suggest that RPA-coated ssDNA is the critical structure at sites of DNA damage that recruits the ATR-ATRIP complex and facilitates its recognition of substrates for phosphorylation and the initiation of checkpoint signaling (PMID:12791985)
• Polyglutamine-expanded proteins strongly activated ATR. (PMID:12915485)
• hyperoxia activates the ATR-Chk1 pathway and phosphorylates p53 at multiple sites in an ATM-independent manner, which is different from other forms of oxidative stress such as H2O2 or UV light. (PMID:12959929)
• A model in which MSH2 and ATR function upstream to regulate two branches of the response pathway to DNA damage caused by MNNG. (PMID:14657349)
• there are at least two in vitro ATR-ATRIP DNA binding complexes, one which binds DNA with high affinity in an RPA-dependent manner and a second, which binds DNA with lower affinity in an RPA-independent manner (PMID:14724280)
• ATR activation is facilitated by phosphorylated H2AX stabilizing ATR at the sites of arrested replication forks (PMID:14742437)
• ATR-p53 pathway is suppressed in noncycling lymphocytes via ATR downregulation. (PMID:14755251)
• The transient slow-down of DNA synthesis was abolished in cells lacking ATR, whereas CHK1-siRNA-treated cells, NBS1 or Fanconi anemia cells showed partial S-phase arrest. (PMID:14988723)
• low-dose UV radiation activates an S-phase checkpoint requiring ATR-mediated signal transduction pathway (PMID:15235112)
• hSMG-1 teams with ATM and ATR to insure the overall quality of the transcriptome in human cells [review] (PMID:15279777)
• ATR serves as a haploinsufficient tumor suppressor in mismatch repair-deficient cells (PMID:15282542)
• ATR checkpoint kinase and RPA1 are required for efficient FANCD2 monoubiquitination (PMID:15314022)
• ATR and Chk1 play critical roles in the cellular response to hypoxia/reoxygenation in cancer cell lines, and inhibitors of ATR and Chk1 represent new hypoxic cell cytotoxins. (PMID:15374968)
• Data show that Artemis interacts with cell cycle checkpoint proteins and is a phosphorylation target of the checkpoint kinases ATM or ATR after exposure of cells to IR or UV irradiation, respectively. (PMID:15456891)
• Effects of ATR on cell radiosensitivity are independent of NHEJ but are linked to HRR that may be affected by the deficient S and G(2) checkpoints. (PMID:15466211)
• N-terminal domain of the ATRIP protein contributes to the cell cycle checkpoint by regulating the intranuclear localization of ATR (PMID:15527801)
• data reveal activated ATM and ATR exhibit selective substrate specificity in response to DNA damage (PMID:15533933)
• Thus, optimal repair of damaged replication fork lesions likely requires both ATR and ATM. BLM recruits 53BP1 to these lesions independent of its helicase activity, and optimal activation of ATM requires both p53 and BLM helicase activities. (PMID:15539948)
• Data suggest that Nijmegen breakage syndrome 1 (Nbs1) functions in both ATR- (ataxia-telangiectasia and Rad3-related protein) and ataxia telangiectasia mutated protein-dependent signalling. (PMID:15616588)
• not required for HIV-1 derived lentivirus vector integration (PMID:15650165)
• Both 53BP1 and NFBD1 are required for recruitment of ATR to DNA damage sites, as well as for ATR-dependent phosphorylation in response to DNA damage. (PMID:15734998)
• ATRIP is required for ATR accumulation at intranuclear foci induced by DNA damage. (PMID:15743907)
• The ATR protein Deltap53 is an essential element of the ATR-intra-S phase checkpoint. (PMID:16009130)
• regulated degradation of histone mRNAs requires regulator of nonsense transcripts 1 delta helicase, a key regulator of the nonsense-mediated decay pathway, and ATR, a key regulator of the DNA damage checkpoint pathway activated during replication stress (PMID:16086026)
• PP5 plays a critical role in ATR-mediated checkpoint activation (PMID:16260606)
• ATM and Mre11 may stimulate the ATR signaling pathway by converting DNA damage generated by ionizing radiation into structures that recruit and activate ATR (PMID:16431910)
• ATR was indentified as a novel mediator of telomere-dependent senescence in response to interstrand cross-link induced by photoactivated psoralens. (PMID:16436511)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	atr	ENSDARG00000079625
mus_musculus	Atr	ENSMUSG00000032409
rattus_norvegicus	Atr	ENSRNOG00000010027
drosophila_melanogaster	mei-41	FBGN0004367

Paralogs (5): ATM (ENSG00000149311), SMG1 (ENSG00000157106), TRRAP (ENSG00000196367), MTOR (ENSG00000198793), PRKDC (ENSG00000253729)

Protein

Protein identifiers

Serine/threonine-protein kinase ATR — Q13535 (reviewed: Q13535)

Alternative names: Ataxia telangiectasia and Rad3-related protein, FRAP-related protein 1

All UniProt accessions (5): A0A590UJ01, D6RFJ6, D6RIG7, Q13535, H0Y8R8

UniProt curated annotations — full annotation on UniProt →

Function. 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. Recognizes the substrate consensus sequence [ST]-Q. 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. Phosphorylates ‘Ser-139’ of histone variant H2AX at sites of DNA damage, thereby regulating DNA damage response mechanism. Required for FANCD2 ubiquitination. Critical for maintenance of fragile site stability and efficient regulation of centrosome duplication. Acts as a regulator of the S-G2 transition by restricting the activity of CDK1 during S-phase to prevent premature entry into G2. Acts as a regulator of the nuclear envelope integrity in response to DNA damage and stress. 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. Also promotes nuclear envelope rupture in response to DNA damage by mediating phosphorylation of LMNA at ‘Ser-282’, leading to lamin disassembly. 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. The rupture of micronuclear envelope triggers the cGAS-STING pathway thereby activating the type I interferon response and innate immunity. Positively regulates the restart of stalled replication forks following activation by the KHDC3L-OOEP scaffold complex.

Subunit / interactions. Forms a heterodimer with ATRIP, forming the ATR-ATRIP complex. Present in a complex containing ATRIP and RPA-coated single-stranded DNA. Binds to DNA, and to UV-damaged DNA with higher affinity. Interacts with MSH2 and HDAC2. Present in a complex containing CHD4 and HDAC2. Interacts with EEF1E1, the interaction is enhanced by UV irradiation. Interacts with CLSPN and CEP164. Interacts with TELO2 and TTI1. Interacts with BCR-ABL after genotoxic stress. Interacts with UHRF2; this interaction promotes ATR activation. Interacts (when phosphorylated) with TOPBP1; interaction takes place when ATR is autophosphorylated at Thr-1989, leading to ATR activation by TOPBP1.

Subcellular location. Nucleus. Chromosome. Nucleus envelope.

Tissue specificity. Ubiquitous, with highest expression in testis. Isoform 2 is found in pancreas, placenta and liver but not in heart, testis and ovary.

Post-translational modifications. Phosphorylated. Autophosphorylation at Thr-1989 in response to DNA damage promotes interaction with TOPBP1 and activation of ATR.

Disease relevance. Seckel syndrome 1 (SCKL1) [MIM:210600] A rare autosomal recessive disorder characterized by proportionate dwarfism of prenatal onset associated with low birth weight, growth retardation, severe microcephaly with a bird-headed like appearance, and intellectual disability. The disease is caused by variants affecting the gene represented in this entry. Cutaneous telangiectasia and cancer syndrome, familial (FCTCS) [MIM:614564] A disease characterized by cutaneous telangiectases in infancy with patchy alopecia over areas of affected skin, thinning of the lateral eyebrows, and mild dental and nail anomalies. Affected individuals are at increased risk of developing oropharyngeal cancer, and other malignancies have been reported as well. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Serine/threonine-protein kinase activity is directly stimulated by TOPBP1. ATR kinase activity is also directly activated by ETAA1, independently of TOPBP1. Activated by DNA and inhibited by BCR-ABL oncogene. Slightly activated by ATRIP. Inhibited by caffeine, wortmannin and LY294002.

Similarity. Belongs to the PI3/PI4-kinase family. ATM subfamily.

Isoforms (3)

UniProt ID	Names	Canonical?
Q13535-1	1	yes
Q13535-2	2
Q13535-3	3

RefSeq proteins (2): NP_001175, NP_001341508 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000403	PI3/4_kinase_cat_dom	Domain
IPR003151	PIK-rel_kinase_FAT	Domain
IPR003152	FATC_dom	Domain
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR011989	ARM-like	Homologous_superfamily
IPR011990	TPR-like_helical_dom_sf	Homologous_superfamily
IPR012993	UME	Domain
IPR014009	PIK_FAT	Domain
IPR016024	ARM-type_fold	Homologous_superfamily
IPR018936	PI3/4_kinase_CS	Conserved_site
IPR021133	HEAT_type_2	Repeat
IPR036940	PI3/4_kinase_cat_sf	Homologous_superfamily
IPR050517	DDR_Repair_Kinase	Family
IPR056802	ATR-like_M-HEAT	Domain
IPR056803	ATR-like_N-HEAT	Domain
IPR057564	HEAT_ATR	Domain

Pfam: PF00454, PF02259, PF02260, PF08064, PF23593, PF25030, PF25032

Enzyme classification (BRENDA):

• EC 2.7.11.1 — non-specific serine/threonine protein kinase (BRENDA: 71 organisms, 682 substrates, 228 inhibitors, 23 Km, 6 kcat entries)

Substrate kinetics (BRENDA)

8 substrates with measured Km, best-characterized 8. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ATP	0.0007–0.64	11
KKRAARATSNVFA	0.013–0.045	3
PAH1 PHOSPHATIDATE PHOSPHATASE	0.0002	2
RRRLSSLRA	0.0036–0.0037	2
GTP	0.46	1
KKRAARASSNVFA	0.02	1
LYS-LYS-PHE-ASN-ARG-THR-LEU-SER-VAL-ALA	0.0093	1
MYELIN BASIC PROTEIN	0.145	1

Catalyzed reactions (Rhea), 2 shown:

• L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H(+) (RHEA:17989)
• L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H(+) (RHEA:46608)

UniProt features (44 total): sequence variant 21, modified residue 4, splice variant 4, mutagenesis site 4, region of interest 4, domain 3, repeat 2, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

10 structures.

PDB	Method	Resolution (Å)
23FC	ELECTRON MICROSCOPY	2.7
9L40	ELECTRON MICROSCOPY	2.87
9L4B	ELECTRON MICROSCOPY	3.2
9L4D	ELECTRON MICROSCOPY	3.79
9L43	ELECTRON MICROSCOPY	3.83
9L45	ELECTRON MICROSCOPY	3.95
9L4C	ELECTRON MICROSCOPY	4.06
5YZ0	ELECTRON MICROSCOPY	4.7
9L4F	ELECTRON MICROSCOPY	6.22
9L46	ELECTRON MICROSCOPY	6.29

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q13535-F1	76.87	0.07

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (4): 428, 435, 436, 1989

Mutagenesis-validated functional residues (4):

Position	Phenotype
1989	impaired autophosphorylation, leading to decreased activation of atr.
2327	abolishes kinase activity.
2475	abolishes kinase activity; increases sensitivity to ir and impairs translocation to nuclear foci upon dna damage.
2494	abolishes kinase activity; reduces cell viability, augments sensitivity to ir and uv.

Function

Pathways and Gene Ontology

Reactome pathways

34 pathways

ID	Pathway
R-HSA-1221632	Meiotic synapsis
R-HSA-176187	Activation of ATR in response to replication stress
R-HSA-3371453	Regulation of HSF1-mediated heat shock response
R-HSA-5685938	HDR through Single Strand Annealing (SSA)
R-HSA-5693607	Processing of DNA double-strand break ends
R-HSA-5693616	Presynaptic phase of homologous DNA pairing and strand exchange
R-HSA-6783310	Fanconi Anemia Pathway
R-HSA-6796648	TP53 Regulates Transcription of DNA Repair Genes
R-HSA-6804756	Regulation of TP53 Activity through Phosphorylation
R-HSA-69473	G2/M DNA damage checkpoint
R-HSA-9709570	Impaired BRCA2 binding to RAD51
R-HSA-1474165	Reproduction
R-HSA-1500620	Meiosis
R-HSA-1640170	Cell Cycle
R-HSA-1643685	Disease
R-HSA-212436	Generic Transcription Pathway
R-HSA-2262752	Cellular responses to stress
R-HSA-3371556	Cellular response to heat stress
R-HSA-3700989	Transcriptional Regulation by TP53
R-HSA-5633007	Regulation of TP53 Activity
R-HSA-5685942	HDR through Homologous Recombination (HRR)
R-HSA-5693532	DNA Double-Strand Break Repair
R-HSA-5693538	Homology Directed Repair
R-HSA-5693567	HDR through Homologous Recombination (HRR) or Single Strand Annealing (SSA)
R-HSA-5693579	Homologous DNA Pairing and Strand Exchange
R-HSA-69481	G2/M Checkpoints
R-HSA-69620	Cell Cycle Checkpoints
R-HSA-73857	RNA Polymerase II Transcription
R-HSA-73894	DNA Repair
R-HSA-74160	Gene expression (Transcription)

MSigDB gene sets: 492 (showing top): PID_FANCONI_PATHWAY, GOBP_DNA_TEMPLATED_DNA_REPLICATION_MAINTENANCE_OF_FIDELITY, GOBP_REGULATION_OF_DOUBLE_STRAND_BREAK_REPAIR, GOBP_RNA_TEMPLATED_DNA_BIOSYNTHETIC_PROCESS, GOBP_CHROMOSOME_ORGANIZATION, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, FLECHNER_PBL_KIDNEY_TRANSPLANT_REJECTED_VS_OK_UP, GOBP_RESPONSE_TO_IONIZING_RADIATION, GOBP_POSITIVE_REGULATION_OF_DNA_DAMAGE_RESPONSE_SIGNAL_TRANSDUCTION_BY_P53_CLASS_MEDIATOR, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, GOBP_POSITIVE_REGULATION_OF_DNA_BIOSYNTHETIC_PROCESS, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, REACTOME_MEIOTIC_SYNAPSIS, GOBP_CELLULAR_RESPONSE_TO_UV, GOBP_MEMBRANE_DISASSEMBLY

GO Biological Process (32): DNA damage checkpoint signaling (GO:0000077), telomere maintenance (GO:0000723), nucleobase-containing compound metabolic process (GO:0006139), DNA replication (GO:0006260), DNA repair (GO:0006281), double-strand break repair (GO:0006302), DNA damage response (GO:0006974), negative regulation of DNA replication (GO:0008156), response to xenobiotic stimulus (GO:0009410), response to mechanical stimulus (GO:0009612), replication fork processing (GO:0031297), positive regulation of telomere maintenance via telomerase (GO:0032212), cellular response to UV (GO:0034644), interstrand cross-link repair (GO:0036297), positive regulation of DNA damage response, signal transduction by p53 class mediator (GO:0043517), mitotic G2/M transition checkpoint (GO:0044818), response to arsenic-containing substance (GO:0046685), nuclear membrane disassembly (GO:0051081), protein localization to chromosome, telomeric region (GO:0070198), cellular response to gamma radiation (GO:0071480), replicative senescence (GO:0090399), establishment of RNA localization to telomere (GO:0097694), establishment of protein-containing complex localization to telomere (GO:0097695), regulation of cellular response to heat (GO:1900034), positive regulation of telomerase catalytic core complex assembly (GO:1904884), regulation of double-strand break repair (GO:2000779), G2/M transition of mitotic cell cycle (GO:0000086), chromatin remodeling (GO:0006338), nuclear envelope organization (GO:0006998), regulation of cellular response to stress (GO:0080135), DNA strand resection involved in replication fork processing (GO:0110025), protein localization to site of double-strand break (GO:1990166)

GO Molecular Function (12): DNA binding (GO:0003677), protein kinase activity (GO:0004672), protein serine/threonine kinase activity (GO:0004674), ATP binding (GO:0005524), MutLalpha complex binding (GO:0032405), MutSalpha complex binding (GO:0032407), histone H2AXS139 kinase activity (GO:0035979), protein serine kinase activity (GO:0106310), nucleotide binding (GO:0000166), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (9): nucleus (GO:0005634), nuclear envelope (GO:0005635), nucleoplasm (GO:0005654), chromosome (GO:0005694), Golgi apparatus (GO:0005794), PML body (GO:0016605), ATR-ATRIP complex (GO:0070310), site of DNA damage (GO:0090734), chromosome, telomeric region (GO:0000781)

Reactome top-level categories

Rollup of top-15 pathways:

Category	Pathways
G2/M Checkpoints	2
HDR through Homologous Recombination (HRR) or Single Strand Annealing (SSA)	2
Transcriptional Regulation by TP53	2
Meiosis	1
Cellular response to heat stress	1
Homologous DNA Pairing and Strand Exchange	1
DNA Repair	1
Regulation of TP53 Activity	1
Defective homologous recombination repair (HRR) due to BRCA2 loss of function	1
Reproduction	1
Cell Cycle	1
RNA Polymerase II Transcription	1
Cellular responses to stimuli	1
Cellular responses to stress	1
Generic Transcription Pathway	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
DNA metabolic process	3
DNA repair	2
response to chemical	2
protein kinase activity	2
mismatch repair complex binding	2
intracellular membrane-bounded organelle	2
endomembrane system	2
cellular anatomical structure	2
DNA integrity checkpoint signaling	1
signal transduction in response to DNA damage	1
telomere organization	1
primary metabolic process	1
DNA biosynthetic process	1
DNA damage response	1
cellular response to stress	1
DNA replication	1
regulation of DNA replication	1
negative regulation of DNA metabolic process	1
response to external stimulus	1
response to abiotic stimulus	1
DNA-templated DNA replication maintenance of fidelity	1
telomere maintenance via telomerase	1
regulation of telomere maintenance via telomerase	1
positive regulation of telomere maintenance via telomere lengthening	1
positive regulation of DNA biosynthetic process	1
response to UV	1
cellular response to light stimulus	1
DNA damage response, signal transduction by p53 class mediator	1
regulation of DNA damage response, signal transduction by p53 class mediator	1
positive regulation of signal transduction by p53 class mediator	1
mitotic cell cycle checkpoint signaling	1
negative regulation of G2/M transition of mitotic cell cycle	1
membrane disassembly	1
nuclear membrane organization	1
protein localization to chromosome	1
response to gamma radiation	1
cellular response to ionizing radiation	1
nucleic acid binding	1
kinase activity	1
phosphotransferase activity, alcohol group as acceptor	1

Protein interactions and networks

STRING

2843 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ATR	ATRIP	Q8WXE1	998
ATR	CHEK2	O96017	955
ATR	CHEK1	O14757	947
ATR	RAD9A	Q99638	922
ATR	RAD17	O75943	918
ATR	TOPBP1	Q92547	907
ATR	HUS1	O60921	872
ATR	XRCC5	P13010	861
ATR	TIMELESS	Q9UNS1	820
ATR	BRCA1	P38398	813
ATR	MDC1	Q14676	810
ATR	CDC45	O75419	803
ATR	RAD52	P43351	801
ATR	RAD51	Q06609	796
ATR	TP53BP1	Q12888	792
ATR	EXO1	Q9UQ84	792

IntAct

159 interactions, top by confidence:

A	B	Type	Score
ATR	ATRIP	psi-mi:“MI:0407”(direct interaction)	0.890
ATR	ATRIP	psi-mi:“MI:0914”(association)	0.890
ATR	ATRIP	psi-mi:“MI:0915”(physical association)	0.890
ATRIP	ATR	psi-mi:“MI:0914”(association)	0.890
TELO2	TTI1	psi-mi:“MI:0914”(association)	0.760
GYPA	TCAF2	psi-mi:“MI:0914”(association)	0.640
SCN2B	EXOC5	psi-mi:“MI:0914”(association)	0.640
VSIG1	TTI1	psi-mi:“MI:0914”(association)	0.640
TNFSF8	TOR1B	psi-mi:“MI:0914”(association)	0.640
CINP	ATR	psi-mi:“MI:0915”(physical association)	0.610
CINP	ATR	psi-mi:“MI:0914”(association)	0.610
PDGFRB	PIK3R2	psi-mi:“MI:0914”(association)	0.610
TELO2	MTOR	psi-mi:“MI:0914”(association)	0.600
TELO2	PRKDC	psi-mi:“MI:0914”(association)	0.600
RUVBL1	TTI1	psi-mi:“MI:0914”(association)	0.600
CDK9	ATR	psi-mi:“MI:0914”(association)	0.560
ATR	CDK9	psi-mi:“MI:0915”(physical association)	0.560
CDC5L	ATR	psi-mi:“MI:0915”(physical association)	0.540
ATR	CDC5L	psi-mi:“MI:0915”(physical association)	0.540
ATR	CDC5L	psi-mi:“MI:0407”(direct interaction)	0.540
GYPB	TCAF2	psi-mi:“MI:0914”(association)	0.530
NCR3LG1	FAM171A2	psi-mi:“MI:0914”(association)	0.530

BioGRID (539): ATR (Affinity Capture-Western), CLTC (Affinity Capture-MS), YBX3 (Affinity Capture-MS), FAM133B (Affinity Capture-MS), PABPN1 (Affinity Capture-MS), ATR (Affinity Capture-MS), ATR (Affinity Capture-MS), ATR (Affinity Capture-MS), ATR (Affinity Capture-MS), ATR (Affinity Capture-MS), ATR (Affinity Capture-MS), ATR (Affinity Capture-MS), ATR (Affinity Capture-MS), ATR (Affinity Capture-MS), ATR (Affinity Capture-MS)

ESM2 similar proteins: A0A2B4RNI3, A0A3M6TIF0, A0A8B8EY61, A0A913XCT1, A6NKT7, B1WBT0, G5ED39, H2QII6, O14715, O36371, O36385, O36386, O36406, P0DJD0, P0DJD1, P24447, P32742, P33802, P34335, P42286, P49792, P52344, P52448, P90245, Q01013, Q01015, Q0VD34, Q13535, Q18LD0, Q23652, Q499E0, Q568Z9, Q5PQN2, Q5R4I8, Q5RBY8, Q6ZN28, Q751Y8, Q76B58, Q7Z3J3, Q8K0S0

Diamond homologs: A2YH41, C5J7W8, O01510, O74630, P0CP60, P0CP61, Q13535, Q2U639, Q4IB89, Q4WVM7, Q5ABX0, Q5BHE2, Q5Z987, Q61CW2, Q6BV76, Q6CAD2, Q6CP76, Q6FRZ9, Q6FX42, Q7RZT9, Q8BKX6, Q95Q95, Q96Q15, Q9DE14, Q9FKS4, Q9JKK8, P38110, P38111, P54676, Q02099, Q13315, Q54ER4, Q59LR2, Q5EAK6, Q62388, Q6P435, Q6PQD5, Q751J3, Q75DB8, Q86C65

SIGNOR signaling

77 interactions.

A	Effect	B	Mechanism
ATR	“up-regulates activity”	BRCA1	phosphorylation
ATR	“up-regulates activity”	RAD17	phosphorylation
ATR	“up-regulates quantity by stabilization”	TP53	phosphorylation
ATR	“down-regulates activity”	MDM2	phosphorylation
ATR	down-regulates	CREB1	phosphorylation
ATR	unknown	MCM2	phosphorylation
ATR	up-regulates	ATRIP	phosphorylation
ATR	up-regulates	CDS1
ATR	up-regulates	CHEK1	phosphorylation
CDKN2A	“up-regulates activity”	ATR	phosphorylation
ATR	up-regulates	XPA	phosphorylation
ATR	up-regulates	PRKDC	phosphorylation
ATR	up-regulates	FANCD2	phosphorylation
ATR	“up-regulates activity”	ATM	phosphorylation
ATR	up-regulates	NBN	phosphorylation
ATR	down-regulates	PI4K2A
ABL1	up-regulates	ATR	phosphorylation
ATR	up-regulates	MCM4	phosphorylation
ATR	up-regulates	MCM6	phosphorylation
ATR	up-regulates	POLH	phosphorylation
MUTYH	up-regulates	ATR	binding
ATR	down-regulates	DBF4	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 158 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell	8	6.8×	8e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

4188 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	96
Likely pathogenic	44
Uncertain significance	2214
Likely benign	1555
Benign	94

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1069016	NM_001184.4(ATR):c.5851C>T (p.Arg1951Ter)	Pathogenic
1072254	NM_001184.4(ATR):c.4915_4918dup (p.Thr1640fs)	Pathogenic
1072974	NC_000003.11:g.(?142272059)(142275427_?)del	Pathogenic
1076365	NM_001184.4(ATR):c.529C>T (p.Arg177Ter)	Pathogenic
1076685	NM_001184.4(ATR):c.5563del (p.His1855fs)	Pathogenic
1076770	NM_001184.4(ATR):c.3402dup (p.Asn1135Ter)	Pathogenic
1357123	NC_000003.12:g.142536202del	Pathogenic
1372183	NM_001184.4(ATR):c.6836dup (p.Asn2279fs)	Pathogenic
1376891	NM_001184.4(ATR):c.5656C>T (p.Arg1886Ter)	Pathogenic
1378337	NM_001184.4(ATR):c.5786_5787insCTAGAAAG (p.Arg1929delinsSerTer)	Pathogenic
1417890	NM_001184.4(ATR):c.5870_5877dup (p.Ala1960fs)	Pathogenic
1421134	NM_001184.4(ATR):c.3567_3568dup (p.Glu1190fs)	Pathogenic
1423201	NM_001184.4(ATR):c.4896dup (p.Leu1633fs)	Pathogenic
1423837	NM_001184.4(ATR):c.2593_2594dup (p.Leu865_Lys866insTer)	Pathogenic
1434427	NM_001184.4(ATR):c.5218dup (p.Val1740fs)	Pathogenic
1444557	NM_001184.4(ATR):c.392T>A (p.Leu131Ter)	Pathogenic
1452399	NM_001184.4(ATR):c.6022C>T (p.Arg2008Ter)	Pathogenic
1453489	NM_001184.4(ATR):c.5679del (p.Tyr1894fs)	Pathogenic
1453747	NM_001184.4(ATR):c.3856C>T (p.Gln1286Ter)	Pathogenic
1454309	NM_001184.4(ATR):c.1885dup (p.Ser629fs)	Pathogenic
1458489	NM_001184.4(ATR):c.7550_7553dup (p.Asn2518delinsLysTer)	Pathogenic
156536	NM_001184.4(ATR):c.3477G>T (p.Met1159Ile)	Pathogenic
1897758	NM_001184.4(ATR):c.1953G>A (p.Trp651Ter)	Pathogenic
1906193	NM_001184.4(ATR):c.5029C>T (p.Gln1677Ter)	Pathogenic
1970626	NM_001184.4(ATR):c.5863dup (p.Leu1955fs)	Pathogenic
2007236	NM_001184.4(ATR):c.4912C>T (p.Gln1638Ter)	Pathogenic
2022356	NM_001184.4(ATR):c.2137C>T (p.Gln713Ter)	Pathogenic
2039249	NM_001184.4(ATR):c.1492C>T (p.Gln498Ter)	Pathogenic
2043590	NM_001184.4(ATR):c.6463G>T (p.Glu2155Ter)	Pathogenic
2044496	NM_001184.4(ATR):c.4507C>T (p.Arg1503Ter)	Pathogenic

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

17471 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:142449444:C:A	W2640C	1.000
3:142449444:C:G	W2640C	1.000
3:142449446:A:G	W2640R	1.000
3:142449446:A:T	W2640R	1.000
3:142458979:A:C	D2494E	1.000
3:142458979:A:T	D2494E	1.000
3:142458980:T:A	D2494V	1.000
3:142458980:T:G	D2494A	1.000
3:142459021:A:C	N2480K	1.000
3:142459021:A:T	N2480K	1.000
3:142459035:G:T	R2476S	1.000
3:142459037:T:A	D2475V	1.000
3:142459037:T:C	D2475G	1.000
3:142459037:T:G	D2475A	1.000
3:142459038:C:G	D2475H	1.000
3:142459040:C:T	G2474E	1.000
3:142459041:C:G	G2474R	1.000
3:142459041:C:T	G2474R	1.000
3:142461997:A:G	W2379R	1.000
3:142461997:A:T	W2379R	1.000
3:142462008:C:T	G2375E	1.000
3:142462009:C:A	G2375W	1.000
3:142465135:C:G	D2335H	1.000
3:142465150:C:G	D2330H	1.000
3:142465157:C:A	K2327N	1.000
3:142465157:C:G	K2327N	1.000
3:142469360:A:G	W2177R	1.000
3:142469360:A:T	W2177R	1.000
3:142469446:C:G	R2148P	1.000
3:142470121:A:G	L2095P	1.000

dbSNP variants (sampled 300 via entrez): RS1000007566 (3:142535838 G>A), RS1000022835 (3:142534290 C>T), RS1000041459 (3:142460848 A>G), RS1000105772 (3:142550107 A>C), RS1000106366 (3:142558213 T>C), RS1000205589 (3:142497781 C>A), RS1000207008 (3:142514726 G>C), RS1000210267 (3:142561885 T>G), RS1000224435 (3:142543596 CCT>C), RS1000225608 (3:142494837 T>C), RS1000249250 (3:142468360 T>G), RS1000264734 (3:142469129 T>C), RS1000309623 (3:142569495 T>A), RS1000323345 (3:142453099 G>T), RS1000358546 (3:142521612 A>G)

Disease associations

OMIM: gene MIM:601215 | disease phenotypes: MIM:210600, MIM:614564, MIM:114480, MIM:122470

GenCC curated gene-disease

Disease	Classification	Inheritance
Seckel syndrome 1	Definitive	Autosomal recessive
sarcoma	Moderate	Autosomal dominant
familial cutaneous telangiectasia and oropharyngeal predisposition cancer syndrome	Moderate	Autosomal dominant
Seckel syndrome	Supportive	Autosomal recessive
familial prostate carcinoma	Limited	Autosomal dominant

Mondo (12): Seckel syndrome 1 (MONDO:0008869), familial cutaneous telangiectasia and oropharyngeal predisposition cancer syndrome (MONDO:0013806), hereditary neoplastic syndrome (MONDO:0015356), hereditary breast carcinoma (MONDO:0016419), Cornelia de Lange syndrome 1 (MONDO:0007387), hereditary breast ovarian cancer syndrome (MONDO:0003582), ATR-X-related syndrome (MONDO:0016980), Seckel syndrome (MONDO:0019342), breast cancer (MONDO:0007254), microcephaly (MONDO:0001149), familial prostate carcinoma (MONDO:0023122), sarcoma (MONDO:0005089)

Orphanet (8): Familial cutaneous telangiectasia and oropharyngeal cancer predisposition syndrome (Orphanet:313846), Seckel syndrome (Orphanet:808), Inherited cancer-predisposing syndrome (Orphanet:140162), Hereditary breast cancer (Orphanet:227535), Cornelia de Lange syndrome (Orphanet:199), Hereditary breast and/or ovarian cancer syndrome (Orphanet:145), Microcephalic primordial dwarfism (Orphanet:324761), OBSOLETE: ATR-X-related syndrome (Orphanet:263355)

HPO phenotypes

1 total (1 of 1 shown, HPO-id order):

HPO	Term
HP:0000252	Microcephaly

GWAS associations

0 associations (top):

MeSH disease descriptors (5)

Descriptor	Name	Tree numbers
D061325	Hereditary Breast and Ovarian Cancer Syndrome	C04.588.180.483; C04.588.322.455.431; C04.700.517; C12.050.351.500.056.630.705.431; C12.050.351.937.418.685.431; C12.100.250.056.630.705.431; C12.900.418.685.431; C16.320.700.517; C17.800.090.500.483; C19.344.410.431; C19.391.630.705.431
D008831	Microcephaly	C05.660.207.620; C10.500.507.400.500; C16.131.621.207.620; C16.131.666.507.400.500
D009386	Neoplastic Syndromes, Hereditary	C04.700; C16.320.700
D012509	Sarcoma	C04.557.450.795
C562840	Breast Cancer, Familial (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (6): CHEMBL3885635 (PROTEIN FAMILY), CHEMBL4106138 (PROTEIN COMPLEX), CHEMBL5024 (SINGLE PROTEIN), CHEMBL5739546 (PROTEIN-PROTEIN INTERACTION), CHEMBL6066136 (PROTEIN-PROTEIN INTERACTION), CHEMBL6066578 (PROTEIN COMPLEX)

Molecules with ChEMBL bioactivity

8 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 12,141 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL4285417	CERALASERTIB	3	1,469
CHEMBL1879463	DACTOLISIB	3	7,988
CHEMBL3989870	BERZOSERTIB	2	1,265
CHEMBL5095260	CAMONSERTIB	2	166
CHEMBL5314933	TUVUSERTIB	2	58
CHEMBL4647810	ELIMUSERTIB	1	297
CHEMBL4650286	M4344	1	521
CHEMBL551064	AEW-541	1	377

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — ATR subfamily

Most potent curated ligand interactions (11 total), top 11:

Ligand	Action	Affinity	Parameter
camonsertib	Inhibition	10.66	pKi
gartisertib	Inhibition	9.82	pKi
berzosertib	Inhibition	9.7	pKi
ceralasertib	Inhibition	9.0	pIC50
AZ20	Inhibition	8.3	pIC50
elimusertib	Inhibition	8.15	pIC50
tuvusertib	Inhibition	8.0	pKi
VE-821	Inhibition	7.89	pKi
dactolisib	Inhibition	7.68	pIC50
alnodesertib	Inhibition	7.3	pIC50
BAY-8400	Inhibition	6.4	pIC50

Binding affinities (BindingDB)

1720 measured of 1901 human assays (1902 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
3-[3-[4-[dideuterio(methylamino)methyl]phenyl]isoxazol-5-yl]-5-(4-isopropylsulfonylphenyl)pyrazin-2-amine	KI	0.148 nM	US-10208027: Processes for preparing ATR inhibitors
US10392376, Example 40b	IC50	0.3 nM	US-10392376: Heterocyclic inhibitors of ATR kinase
1-Methyl-7-(3-methyl-3H-imidazol-4-yl)-5-((R)-3-methyl-morpholin-4-yl)-3-(1H-pyrazol-3-yl)-1H-pyrazolo[4,3-b]pyridine	IC50	0.3 nM	US-12371430: 5-morpholin-4-yl-pyrazolo[4,3-b]pyridine derivatives
US10392376, Example 44b	IC50	0.4 nM	US-10392376: Heterocyclic inhibitors of ATR kinase
US10392376, Example 86	IC50	0.4 nM	US-10392376: Heterocyclic inhibitors of ATR kinase
(3R)-3-Methyl-4-[1-methyl-7-(4-methylpyrimidin-5-yl)-3-(1H-pyrazol-3-yl)-1H-pyrazolo[4,3-b]pyridin-5-yl]morpholine	IC50	0.4 nM	US-12371430: 5-morpholin-4-yl-pyrazolo[4,3-b]pyridine derivatives
[2-[2-(fluoromethyl)benzimidazol-1-yl]-6-[(3R)-3-methylmorpholin-4-yl]pyrimidin-4-yl]imino-dimethyl-oxo-lambda6-sulfane	IC50	0.5 nM	US-10392376: Heterocyclic inhibitors of ATR kinase
(3R)-3-Methyl-4-[7-(2-methylphenyl)-3-(1H-pyrazol-3-yl)-1H-pyrazolo[4,3-b]pyridin-5-yl]morpholine	IC50	0.5 nM	US-12371430: 5-morpholin-4-yl-pyrazolo[4,3-b]pyridine derivatives
3-[3-[4-[(3R)-morpholin-3-yl]phenyl]-1,2-oxazol-5-yl]-5-(4-propan-2-ylsulfonylphenyl)pyrazin-2-amine	KI	0.503 nM	US-20130089624: Compounds Useful as Inhibitors of ATR Kinase
1-(3-methoxycyclobutyl)-8-[6-(3-pyrrolidin-1-ylpropoxy)-3-pyridinyl]-3H-imidazo[4,5-c]quinolin-2-one	IC50	0.589 nM	US-9428503: Imidazo[4,5-c]quinolin-2-one compounds and their use in treating Cancer
1-Methyl-5-((R)-3-methyl-morpholin-4-yl)-3-(1H-pyrazol-3-yl)-7-(1H-pyrrolo[2,3-b]pyridin-4-yl)-1H-pyrazolo[4,3-b]pyridine	IC50	0.6 nM	US-12371430: 5-morpholin-4-yl-pyrazolo[4,3-b]pyridine derivatives
7-[2-(2-Fluoro-ethyl)-2H-pyrazol-3-yl]-1-methyl-5-((R)-3-methyl-morpholin-4-yl)-3-(1H-pyrazol-3-yl)-1H-pyrazolo[4,3-b]pyridine	IC50	0.6 nM	US-12371430: 5-morpholin-4-yl-pyrazolo[4,3-b]pyridine derivatives
(3R)-3-Methyl-4-[1-methyl-7-(1-methyl-1H-pyrazol-5-yl)-3-(1H-pyrazol-3-yl)-1H-pyrazolo[4,3-b]pyridin-5-yl]morpholine	IC50	0.6 nM	US-12371430: 5-morpholin-4-yl-pyrazolo[4,3-b]pyridine derivatives
US10392376, Example 38b	IC50	0.7 nM	US-10392376: Heterocyclic inhibitors of ATR kinase
1-Methyl-5-((R)-3-methyl-morpholin-4-yl)-3-(2H-pyrazol-3-yl)-7-(tetrahydro-pyran-4-yl)-1H-pyrazolo[4,3-b]pyridine	IC50	0.7 nM	US-12371430: 5-morpholin-4-yl-pyrazolo[4,3-b]pyridine derivatives
US10392376, Example 41b	IC50	0.8 nM	US-10392376: Heterocyclic inhibitors of ATR kinase
5-((R)-3-Methyl-morpholin-4-yl)-7-(6-methyl-pyridin-3-yl)-3-(1H-pyrazol-3-yl)-1H-pyrazolo[4,3-b]pyridine	IC50	0.8 nM	US-12371430: 5-morpholin-4-yl-pyrazolo[4,3-b]pyridine derivatives
1-Methyl-5-((R)-3-methyl-morpholin-4-yl)-7-(2-methyl-pyridin-3-yl)-3-(1H-pyrazol-3-yl)-1H-pyrazolo[4,3-b]pyridine	IC50	0.8 nM	US-12371430: 5-morpholin-4-yl-pyrazolo[4,3-b]pyridine derivatives
7-(6-Methanesulfonyl-2-methyl-pyridin-3-yl)-5-((R)-3-methyl-morpholin-4-yl)-3-(1H-pyrazol-3-yl)-1H-pyrazolo[4,3-b]pyridine	IC50	0.8 nM	US-12371430: 5-morpholin-4-yl-pyrazolo[4,3-b]pyridine derivatives
7-(1-Methanesulfonyl-cyclopropyl)-1-methyl-5-((R)-3-methyl-morpholin-4-yl)-3-(1H-pyrazol-3-yl)-1H-pyrazolo[4,3-b]pyridine	IC50	0.8 nM	US-12371430: 5-morpholin-4-yl-pyrazolo[4,3-b]pyridine derivatives
1-Methyl-5-((R)-3-methyl-morpholin-4-yl)-3-(2H-pyrazol-3-yl)-7-(tetrahydro-pyran-3-yl)-1H-pyrazolo[4,3-b]pyridine	IC50	0.8 nM	US-12371430: 5-morpholin-4-yl-pyrazolo[4,3-b]pyridine derivatives
4-[1-Methyl-5-[(3R)-3-methylmorpholin-4-yl]-3-(1H-pyrazol-5-yl)-1H-pyrazolo[4,3-b]pyridin-7-yl]-2H-1lambda6-thiopyran-1,1-dione	IC50	0.8 nM	US-12371430: 5-morpholin-4-yl-pyrazolo[4,3-b]pyridine derivatives
US10392376, Example 52	IC50	0.9 nM	US-10392376: Heterocyclic inhibitors of ATR kinase
US10392376, Example 95	IC50	0.9 nM	US-10392376: Heterocyclic inhibitors of ATR kinase
(3R)-3-Methyl-4-[3-(3-methyl-1H-pyrazol-5-yl)-7-(6-methylpyridin-3-yl)-1H-pyrazolo[4,3-b]pyridin-5-yl]morpholine	IC50	0.9 nM	US-12371430: 5-morpholin-4-yl-pyrazolo[4,3-b]pyridine derivatives
(3R)-4-[7-(6-Methanesulfonyl-2-methylpyridin-3-yl)-1-methyl-3-(1H-pyrazol-3-yl)-1H-pyrazolo[4,3-b]pyridin-5-yl]-3-methylmorpholine	IC50	0.9 nM	US-12371430: 5-morpholin-4-yl-pyrazolo[4,3-b]pyridine derivatives
(3R)-4-[7-(1-Methanesulfonylethyl)-1-methyl-3-(1H-pyrazol-3-yl)-1H-pyrazolo[4,3-b]pyridin-5-yl]-3-methylmorpholine	IC50	0.9 nM	US-12371430: 5-morpholin-4-yl-pyrazolo[4,3-b]pyridine derivatives
US10392376, Example 1	IC50	1 nM	US-10392376: Heterocyclic inhibitors of ATR kinase
US10392376, Example 46b	IC50	1 nM	US-10392376: Heterocyclic inhibitors of ATR kinase
cyclopropyl-methyl-[6-[(3R)-3-methylmorpholin-4-yl]-2-(1H-pyrrolo[2,3-b]pyridin-4-yl)pyrimidin-4-yl]imino-oxo-lambda6-sulfane	IC50	1 nM	US-11434233: Heterocyclic inhibitors of ATR kinase
1-Methyl-5-((R)-3-methyl-morpholin-4-yl)-7-(3-methyl-pyridin-4-yl)-3-(1H-pyrazol-3-yl)-1H-pyrazolo[4,3-b]pyridine	IC50	1 nM	US-12371430: 5-morpholin-4-yl-pyrazolo[4,3-b]pyridine derivatives
8-[6-[3-(dimethylamino)propoxy]-3-pyridinyl]-1-(3-methoxycyclobutyl)-3H-imidazo[4,5-c]quinolin-2-one	IC50	1.03 nM	US-9428503: Imidazo[4,5-c]quinolin-2-one compounds and their use in treating Cancer
7-(3-Fluoro-pyridin-4-yl)-1-methyl-5-((R)-3-methyl-morpholin-4-yl)-3-(1H-pyrazol-3-yl)-1H-pyrazolo[4,3-b]pyridine	IC50	1.2 nM	US-12371430: 5-morpholin-4-yl-pyrazolo[4,3-b]pyridine derivatives
(3R)-4-{7-[4-(Methoxymethyl)phenyl]-1-methyl-3-(1H-pyrazol-3-yl)-1H-pyrazolo[4,3-b]pyridin-5-yl}-3-methylmorpholine	IC50	1.2 nM	US-12371430: 5-morpholin-4-yl-pyrazolo[4,3-b]pyridine derivatives
(3R)-4-[7-(4-Methanesulfonylphenyl)-1-(propan-2-yl)-3-(1H-pyrazol-3-yl)-1H-pyrazolo[4,3-b]pyridin-5-yl]-3-methylmorpholine	IC50	1.3 nM	US-12371430: 5-morpholin-4-yl-pyrazolo[4,3-b]pyridine derivatives
(3R)-4-[7-(4-Methanesulfonyl-2-methylphenyl)-1-methyl-3-(1H-pyrazol-3-yl)-1H-pyrazolo[4,3-b]pyridin-5-yl]-3-methylmorpholine	IC50	1.3 nM	US-12371430: 5-morpholin-4-yl-pyrazolo[4,3-b]pyridine derivatives
(3R)-4-[7-(6-Methanesulfonyl-2-methylpyridin-3-yl)-3-(3-methyl-1H-pyrazol-5-yl)-1H-pyrazolo[4,3-b]pyridin-5-yl]-3-methylmorpholine	IC50	1.4 nM	US-12371430: 5-morpholin-4-yl-pyrazolo[4,3-b]pyridine derivatives
(4-{1-Methyl-5-[(3R)-3-methylmorpholin-4-yl]-3-(1H-pyrazol-3-yl)-1H-pyrazolo[4,3-b]pyridin-7-yl}phenyl)methanol	IC50	1.4 nM	US-12371430: 5-morpholin-4-yl-pyrazolo[4,3-b]pyridine derivatives
US10392376, Example 31	IC50	1.6 nM	US-10392376: Heterocyclic inhibitors of ATR kinase
(3R)-3-Methyl-4-[1-methyl-7-(2-methylphenyl)-3-(1H-pyrazol-5-yl)-1H-pyrazolo[4,3-b]pyridin-5-yl]morpholine	IC50	1.8 nM	US-12371430: 5-morpholin-4-yl-pyrazolo[4,3-b]pyridine derivatives
(3R)-4-(7-{6-[(R)-Methanesulfinyl]-2-methylpyridin-3-yl}-1-methyl-3-(1H-pyrazol-3-yl)-1H-pyrazolo[4,3-b]pyridin-5-yl)-3-methylmorpholine	IC50	1.9 nM	US-12371430: 5-morpholin-4-yl-pyrazolo[4,3-b]pyridine derivatives
(3R)-3-Methyl-4-[1-methyl-3-(1H-pyrazol-3-yl)-7-[2-(trifluoro-methyl)pyridin-3-yl]-1H-pyrazolo[4,3-b]pyridin-5-yl]morpholine	IC50	1.9 nM	US-12371430: 5-morpholin-4-yl-pyrazolo[4,3-b]pyridine derivatives
US10392376, Example 3	IC50	2 nM	US-10392376: Heterocyclic inhibitors of ATR kinase
US10392376, Example 56	IC50	2 nM	US-10392376: Heterocyclic inhibitors of ATR kinase
US10392376, Example 64	IC50	2 nM	US-10392376: Heterocyclic inhibitors of ATR kinase
US10392376, Example 71	IC50	2 nM	US-10392376: Heterocyclic inhibitors of ATR kinase
US10392376, Example 88	IC50	2 nM	US-10392376: Heterocyclic inhibitors of ATR kinase
US10392376, Example 108	IC50	2 nM	US-10392376: Heterocyclic inhibitors of ATR kinase
US10392376, Example 109	IC50	2 nM	US-10392376: Heterocyclic inhibitors of ATR kinase
diethyl({6-[(3R)-3-methylmorpholin- 4-yl]-2-{1H-pyrrolo[2,3-b]pyridin-4- yl}pyrimidin-4-yl}imino)-lambda6- sulfanone	IC50	2 nM	US-10894052: Heterocyclic inhibitors of ATR kinase

ChEMBL bioactivities

5524 potent at pChembl≥5 of 5571 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.22	Ki	0.06	nM	CERALASERTIB
10.00	IC50	0.1	nM	CHEMBL3355476
9.85	Ki	0.14	nM	CHEMBL4444602
9.83	Ki	0.148	nM	BERZOSERTIB
9.82	IC50	0.15	nM	M4344
9.78	Ki	0.165	nM	BERZOSERTIB
9.77	IC50	0.17	nM	BERZOSERTIB
9.70	IC50	0.2	nM	CHEMBL3355474
9.70	Ki	0.2	nM	BERZOSERTIB
9.68	Ki	0.21	nM	CHEMBL4533440
9.57	Ki	0.27	nM	CHEMBL4443525
9.52	IC50	0.3	nM	CHEMBL3355072
9.52	IC50	0.3	nM	CHEMBL5783158
9.48	IC50	0.33	nM	CAMONSERTIB
9.40	IC50	0.4	nM	CHEMBL3355074
9.40	IC50	0.4	nM	CHEMBL3355475
9.40	IC50	0.4	nM	CHEMBL5786594
9.40	IC50	0.4	nM	CHEMBL6010318
9.30	IC50	0.5	nM	CHEMBL3355069
9.30	IC50	0.5	nM	CHEMBL3355071
9.30	IC50	0.5	nM	CHEMBL3355480
9.30	Ki	0.503	nM	CHEMBL3642117
9.30	IC50	0.5	nM	CHEMBL5775367
9.28	Ki	0.53	nM	CHEMBL4566104
9.22	IC50	0.6	nM	ELIMUSERTIB
9.15	IC50	0.7	nM	CHEMBL5800832
9.12	Ki	0.75	nM	CHEMBL4448538
9.10	IC50	0.8	nM	CHEMBL5567701
9.10	IC50	0.8	nM	CHEMBL5783158
9.10	IC50	0.8	nM	CHEMBL5800499
9.05	IC50	0.9	nM	CAMONSERTIB
9.05	IC50	0.9	nM	CHEMBL5761609
9.05	IC50	0.9	nM	CHEMBL5928836
9.00	IC50	1	nM	CHEMBL3355070
9.00	IC50	1	nM	CHEMBL3355073
9.00	IC50	1	nM	CHEMBL3355473
9.00	IC50	1	nM	CHEMBL4293269
9.00	IC50	1	nM	CHEMBL4288033
9.00	Ki	1	nM	CHEMBL4434665
9.00	Ki	1	nM	CHEMBL4440048
9.00	Ki	1	nM	CHEMBL4467820
9.00	IC50	1	nM	CHEMBL5394792
9.00	IC50	1	nM	CERALASERTIB
9.00	IC50	1	nM	CHEMBL5790125
9.00	IC50	1	nM	CHEMBL5957036
9.00	IC50	1	nM	CHEMBL5829979
9.00	IC50	1	nM	CAMONSERTIB
9.00	IC50	1	nM	CHEMBL5173530
8.96	IC50	1.1	nM	M4344
8.92	IC50	1.2	nM	CHEMBL5417125

PubChem BioAssay actives

625 with measured affinity, of 1273 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
3-[3-[4-(methylaminomethyl)phenyl]-1,2-oxazol-5-yl]-5-(4-propan-2-ylsulfonylphenyl)pyrazin-2-amine	2067683: Inhibition of ATR (unknown origin) by Morrison equation based analysis	ki	<0.0001	uM
(3R)-4-[6-(5-fluoro-1H-pyrrolo[2,3-c]pyridin-4-yl)-1-methylimidazo[4,5-c]pyridin-4-yl]-3-methylmorpholine	1177189: Inhibition of human ATR using ATP substrate measured after 3 hrs	ic50	0.0001	uM
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	2067683: Inhibition of ATR (unknown origin) by Morrison equation based analysis	ki	0.0001	uM
3-[3-[4-[(oxan-4-ylamino)methyl]phenyl]-1,2-oxazol-5-yl]-5-(4-propan-2-ylsulfonylphenyl)pyrazin-2-amine	1555163: Inhibition of recombinant human full-length N-terminal Flag epitope-tagged ATR expressed in HEK293T cells using ASELPASQPQPFSAKKK peptide as substrate measured after 24 hrs in presence of [gamma-33P] ATP by microbeta liquid scintillation counting analysis	ki	0.0001	uM
2-amino-6-fluoro-N-[5-fluoro-4-[4-[4-(oxetan-3-yl)piperazine-1-carbonyl]piperidin-1-yl]-3-pyridinyl]pyrazolo[1,5-a]pyrimidine-3-carboxamide	1872291: Binding affinity to ATR (unknown origin) assessed as inhibition constant	ki	0.0001	uM
(3R)-3-methyl-4-[1-[(1R)-1-methylsulfonylethyl]-6-(1H-pyrrolo[2,3-c]pyridin-4-yl)imidazo[4,5-c]pyridin-4-yl]morpholine	1177189: Inhibition of human ATR using ATP substrate measured after 3 hrs	ic50	0.0002	uM
3-[3-[4-(ethylaminomethyl)phenyl]-1,2-oxazol-5-yl]-5-(4-propan-2-ylsulfonylphenyl)pyrazin-2-amine	1555163: Inhibition of recombinant human full-length N-terminal Flag epitope-tagged ATR expressed in HEK293T cells using ASELPASQPQPFSAKKK peptide as substrate measured after 24 hrs in presence of [gamma-33P] ATP by microbeta liquid scintillation counting analysis	ki	0.0002	uM
(6R)-6-methyl-3-(4-methylsulfonylphenyl)-5-(1H-pyrrolo[2,3-b]pyridin-4-yl)-6,7-dihydro-4H-pyrazolo[1,5-a]pyrazine	1177170: Inhibition of ATR (unknown origin) using Avi-tagged protein substrate by alphascreen assay	ic50	0.0003	uM
(1R,5S)-3-[6-[(3R)-3-methylmorpholin-4-yl]-1-(1H-pyrazol-5-yl)pyrazolo[5,4-b]pyridin-4-yl]-8-oxabicyclo[3.2.1]octan-3-ol	2067712: Inhibition of ATR in gemcitabine-stimulated human LoVo cells assessed as decrease in CHK1 phosphorylation at Ser345 residue	ic50	0.0003	uM
3-[3-[4-(aminomethyl)phenyl]-1,2-oxazol-5-yl]-5-(4-propan-2-ylsulfonylphenyl)pyrazin-2-amine	1555163: Inhibition of recombinant human full-length N-terminal Flag epitope-tagged ATR expressed in HEK293T cells using ASELPASQPQPFSAKKK peptide as substrate measured after 24 hrs in presence of [gamma-33P] ATP by microbeta liquid scintillation counting analysis	ki	0.0003	uM
(6R)-5-(6-chloro-1H-pyrrolo[2,3-b]pyridin-4-yl)-6-methyl-3-(1-methylsulfonylpiperidin-4-yl)-6,7-dihydro-4H-pyrazolo[1,5-a]pyrazine	1177170: Inhibition of ATR (unknown origin) using Avi-tagged protein substrate by alphascreen assay	ic50	0.0004	uM
(3R)-3-methyl-4-[1-methyl-6-(1H-pyrrolo[2,3-c]pyridin-4-yl)imidazo[4,5-c]pyridin-4-yl]morpholine	1177189: Inhibition of human ATR using ATP substrate measured after 3 hrs	ic50	0.0004	uM
N,N-dimethyl-4-[6-(1H-pyrrolo[2,3-b]pyridin-4-yl)imidazo[1,2-b]pyridazin-3-yl]benzenesulfonamide	1177170: Inhibition of ATR (unknown origin) using Avi-tagged protein substrate by alphascreen assay	ic50	0.0005	uM
(3R)-3-methyl-4-[1-methyl-6-(1H-pyrrolo[2,3-d]pyridazin-4-yl)imidazo[4,5-c]pyridin-4-yl]morpholine	1177189: Inhibition of human ATR using ATP substrate measured after 3 hrs	ic50	0.0005	uM
3-[3-[4-[(1R)-1-aminoethyl]phenyl]-1,2-oxazol-5-yl]-5-(4-propan-2-ylsulfonylphenyl)pyrazin-2-amine	1555163: Inhibition of recombinant human full-length N-terminal Flag epitope-tagged ATR expressed in HEK293T cells using ASELPASQPQPFSAKKK peptide as substrate measured after 24 hrs in presence of [gamma-33P] ATP by microbeta liquid scintillation counting analysis	ki	0.0005	uM
N,N-dimethyl-4-[(6R)-6-methyl-5-(1H-pyrrolo[2,3-b]pyridin-4-yl)-6,7-dihydro-4H-pyrazolo[1,5-a]pyrazin-3-yl]benzenesulfonamide	1177170: Inhibition of ATR (unknown origin) using Avi-tagged protein substrate by alphascreen assay	ic50	0.0005	uM
(3R)-3-methyl-4-[4-(2-methylpyrazol-3-yl)-8-(1H-pyrazol-5-yl)-1,7-naphthyridin-2-yl]morpholine	2067712: Inhibition of ATR in gemcitabine-stimulated human LoVo cells assessed as decrease in CHK1 phosphorylation at Ser345 residue	ic50	0.0006	uM
2-methyl-2-[6-[(3R)-3-methylmorpholin-4-yl]-1-(1H-pyrazol-5-yl)pyrazolo[5,4-b]pyridin-4-yl]propanenitrile	2067684: Inhibition of ATR in human HeLa S3 cells assessed as decrease in CHK1 phosphorylation at Ser345 residue pretreated for 20 mins followed by gemcitabine stimulation for 3.5 to 4 hrs by AlphaScreen SurFire assay	ic50	0.0008	uM
3-[3-[2-chloro-4-(methylaminomethyl)phenyl]-1,2-oxazol-5-yl]-5-(4-propan-2-ylsulfonylphenyl)pyrazin-2-amine	1555163: Inhibition of recombinant human full-length N-terminal Flag epitope-tagged ATR expressed in HEK293T cells using ASELPASQPQPFSAKKK peptide as substrate measured after 24 hrs in presence of [gamma-33P] ATP by microbeta liquid scintillation counting analysis	ki	0.0008	uM
N,N-dimethyl-4-[5-(1H-pyrrolo[2,3-b]pyridin-4-yl)-6,7-dihydro-4H-pyrazolo[1,5-a]pyrazin-3-yl]benzenesulfonamide	1177170: Inhibition of ATR (unknown origin) using Avi-tagged protein substrate by alphascreen assay	ic50	0.0010	uM
(6R)-6-methyl-3-(1-methylsulfonylpiperidin-4-yl)-5-(1H-pyrrolo[2,3-b]pyridin-4-yl)-6,7-dihydro-4H-pyrazolo[1,5-a]pyrazine	1177170: Inhibition of ATR (unknown origin) using Avi-tagged protein substrate by alphascreen assay	ic50	0.0010	uM
(3R)-4-[6-(1H-indol-4-yl)-1-(methylsulfonylmethyl)imidazo[4,5-c]pyridin-4-yl]-3-methylmorpholine	1177189: Inhibition of human ATR using ATP substrate measured after 3 hrs	ic50	0.0010	uM
N-methyl-1-[(10S,14R)-14-methyl-6-(2-methylsulfonylpropan-2-yl)-8,12-dioxa-1,3,5-triazatricyclo[8.4.0.02,7]tetradeca-2,4,6-trien-4-yl]benzimidazol-2-amine	1410235: Inhibition of recombinant human full length ATR/ATRIP expressed in mammalian expression system using c-Myc-tagged p53 as substrate incubated for 15 mins followed by substrate addition measured after 25 to 35 mins by TR-FRET assay	ic50	0.0010	uM
N-methyl-4-[(10S,14R)-14-methyl-6-(2-methylsulfonylpropan-2-yl)-8,12-dioxa-1,3,5-triazatricyclo[8.4.0.02,7]tetradeca-2,4,6-trien-4-yl]-1H-pyrrolo[2,3-b]pyridin-5-amine	1410235: Inhibition of recombinant human full length ATR/ATRIP expressed in mammalian expression system using c-Myc-tagged p53 as substrate incubated for 15 mins followed by substrate addition measured after 25 to 35 mins by TR-FRET assay	ic50	0.0010	uM
2-[(10S,14R)-14-methyl-4-[5-(methylamino)-1H-pyrrolo[2,3-b]pyridin-4-yl]-8,12-dioxa-1,3,5-triazatricyclo[8.4.0.02,7]tetradeca-2,4,6-trien-6-yl]propan-2-ol	1410235: Inhibition of recombinant human full length ATR/ATRIP expressed in mammalian expression system using c-Myc-tagged p53 as substrate incubated for 15 mins followed by substrate addition measured after 25 to 35 mins by TR-FRET assay	ic50	0.0010	uM
N-ethyl-4-[(10S,14R)-14-methyl-6-(2-methylsulfonylpropan-2-yl)-8,12-dioxa-1,3,5-triazatricyclo[8.4.0.02,7]tetradeca-2,4,6-trien-4-yl]-1H-pyrrolo[2,3-b]pyridin-5-amine	1410235: Inhibition of recombinant human full length ATR/ATRIP expressed in mammalian expression system using c-Myc-tagged p53 as substrate incubated for 15 mins followed by substrate addition measured after 25 to 35 mins by TR-FRET assay	ic50	0.0010	uM
1-[4-[(3R)-3-methylmorpholin-4-yl]-6-(1-methylsulfonylcyclopropyl)pyrimidin-2-yl]benzimidazol-2-amine	1423055: Inhibition of ATR in human HeLa cell nuclear extract using GST-fused p53N66 as substrate preincubated for 10 mins followed by ATP addition and measured after 1 hr by ELISA	ic50	0.0010	uM
3-(5-phenyl-1,3,4-thiadiazol-2-yl)-5-(4-propan-2-ylsulfonylphenyl)pyrazin-2-amine	1555163: Inhibition of recombinant human full-length N-terminal Flag epitope-tagged ATR expressed in HEK293T cells using ASELPASQPQPFSAKKK peptide as substrate measured after 24 hrs in presence of [gamma-33P] ATP by microbeta liquid scintillation counting analysis	ki	0.0010	uM
3-(3-phenyl-1,2-oxazol-5-yl)-5-(4-propan-2-ylsulfonylphenyl)pyrazin-2-amine	1555163: Inhibition of recombinant human full-length N-terminal Flag epitope-tagged ATR expressed in HEK293T cells using ASELPASQPQPFSAKKK peptide as substrate measured after 24 hrs in presence of [gamma-33P] ATP by microbeta liquid scintillation counting analysis	ki	0.0010	uM
1-[4-[(3R)-3-methylmorpholin-4-yl]-7-methylsulfonylthieno[3,2-d]pyrimidin-2-yl]benzimidazol-2-amine	1970596: Inhibition of ATR (unknown origin)	ic50	0.0010	uM
3-(5-phenyl-1,3,4-oxadiazol-2-yl)-5-(4-propan-2-ylsulfonylphenyl)pyrazin-2-amine	1555163: Inhibition of recombinant human full-length N-terminal Flag epitope-tagged ATR expressed in HEK293T cells using ASELPASQPQPFSAKKK peptide as substrate measured after 24 hrs in presence of [gamma-33P] ATP by microbeta liquid scintillation counting analysis	ki	0.0010	uM
3-[3-[4-[(1S)-1-aminoethyl]phenyl]-1,2-oxazol-5-yl]-5-(4-propan-2-ylsulfonylphenyl)pyrazin-2-amine	1555163: Inhibition of recombinant human full-length N-terminal Flag epitope-tagged ATR expressed in HEK293T cells using ASELPASQPQPFSAKKK peptide as substrate measured after 24 hrs in presence of [gamma-33P] ATP by microbeta liquid scintillation counting analysis	ki	0.0012	uM
5-fluoro-1-[4-[(3R)-3-methylmorpholin-4-yl]-7-methylsulfonylthieno[3,2-d]pyrimidin-2-yl]benzimidazol-2-amine	1970596: Inhibition of ATR (unknown origin)	ic50	0.0012	uM
1-[6-[(3R)-3-methylmorpholin-4-yl]-1-(1H-pyrazol-5-yl)pyrazolo[5,4-b]pyridin-4-yl]cyclohexan-1-ol	2067684: Inhibition of ATR in human HeLa S3 cells assessed as decrease in CHK1 phosphorylation at Ser345 residue pretreated for 20 mins followed by gemcitabine stimulation for 3.5 to 4 hrs by AlphaScreen SurFire assay	ic50	0.0013	uM
2,2,3,3,4,4,5,5,6,6-decadeuterio-1-[6-[(3R)-3-methylmorpholin-4-yl]-1-(1H-pyrazol-5-yl)pyrazolo[5,4-b]pyridin-4-yl]cyclohexan-1-ol	2067684: Inhibition of ATR in human HeLa S3 cells assessed as decrease in CHK1 phosphorylation at Ser345 residue pretreated for 20 mins followed by gemcitabine stimulation for 3.5 to 4 hrs by AlphaScreen SurFire assay	ic50	0.0015	uM
N-methyl-1-[4-[(3R)-3-methylmorpholin-4-yl]-7-methylsulfonylthieno[3,2-d]pyrimidin-2-yl]benzimidazol-2-amine	1970596: Inhibition of ATR (unknown origin)	ic50	0.0015	uM
(3R)-3-methyl-4-[7-methylsulfonyl-2-(1H-pyrrolo[2,3-c]pyridin-4-yl)pyrrolo[2,3-d]pyrimidin-4-yl]morpholine	2086900: Inhibition of ATR/ATRIP (unknown origin) using 5-FAM-AK-17 as substrate preincubated with compound for 10 mins followed by ATP addition and measured after 240 mins by mobility shift assay	ic50	0.0016	uM
(3R)-3-methyl-4-[7-methylsulfonyl-2-(1H-pyrrolo[2,3-b]pyridin-4-yl)pyrrolo[2,3-d]pyrimidin-4-yl]morpholine	2086900: Inhibition of ATR/ATRIP (unknown origin) using 5-FAM-AK-17 as substrate preincubated with compound for 10 mins followed by ATP addition and measured after 240 mins by mobility shift assay	ic50	0.0016	uM
7-[(6R)-6-methyl-3-(1-methylsulfonylpiperidin-4-yl)-6,7-dihydro-4H-pyrazolo[1,5-a]pyrazin-5-yl]-1H-imidazo[4,5-b]pyridine	1177170: Inhibition of ATR (unknown origin) using Avi-tagged protein substrate by alphascreen assay	ic50	0.0020	uM
3,3-dimethyl-2-[2-[(3R)-3-methylmorpholin-4-yl]-8-(1H-pyrazol-5-yl)-1,7-naphthyridin-4-yl]butan-2-ol	1652460: Inhibition of 5’-TAMRA-labeled tracer 3’,6’-bis(dimethylamino)-N-(4-{[2(1H-indol-4-yl)-6-(morpholin-4-yl)-pyrimidin-4-yl]amino}butyl)-3-oxo-3H-spiro[2-benzofuran-1,9’-xanthene]-5-carboxamide binding to recombinant human full-length N-terminal Flag-tagged ATR expressed in HEK293-6E cells co-expressing human full-length STREP-tagged ATRIP preincubated for 10 mins followed by tracer addition and measured after 30 mins by TR-FRET assay	ic50	0.0020	uM
(3R)-3-methyl-4-[6-(1-methylsulfonylcyclopropyl)-2-(1H-pyrrolo[2,3-c]pyridin-4-yl)pyrimidin-4-yl]morpholine	1423055: Inhibition of ATR in human HeLa cell nuclear extract using GST-fused p53N66 as substrate preincubated for 10 mins followed by ATP addition and measured after 1 hr by ELISA	ic50	0.0020	uM
N-methyl-1-[4-[(3R)-3-methylmorpholin-4-yl]-6-(1-methylsulfonylcyclopropyl)pyrimidin-2-yl]benzimidazol-2-amine	1423055: Inhibition of ATR in human HeLa cell nuclear extract using GST-fused p53N66 as substrate preincubated for 10 mins followed by ATP addition and measured after 1 hr by ELISA	ic50	0.0020	uM
5-fluoro-1-[4-[(3R)-3-methylmorpholin-4-yl]-6-(1-methylsulfonylcyclopropyl)pyrimidin-2-yl]benzimidazol-2-amine	1423055: Inhibition of ATR in human HeLa cell nuclear extract using GST-fused p53N66 as substrate preincubated for 10 mins followed by ATP addition and measured after 1 hr by ELISA	ic50	0.0020	uM
3-(5-phenyl-1,2-oxazol-3-yl)-5-(4-propan-2-ylsulfonylphenyl)pyrazin-2-amine	1555163: Inhibition of recombinant human full-length N-terminal Flag epitope-tagged ATR expressed in HEK293T cells using ASELPASQPQPFSAKKK peptide as substrate measured after 24 hrs in presence of [gamma-33P] ATP by microbeta liquid scintillation counting analysis	ki	0.0020	uM
1-[2-(1H-indol-4-yl)-7,7-dimethyl-4-[(3R)-3-methylmorpholin-4-yl]-5H-pyrrolo[3,4-d]pyrimidin-6-yl]ethanone	1979993: Inhibition of ATR (unknown origin) using peptide as substrate preincubated for 10 mins followed by substrate addition by microplate reader analysis	ic50	0.0020	uM
1-[2-(1H-indol-4-yl)-7,7-dimethyl-4-[(3R)-3-methylmorpholin-4-yl]-5H-pyrrolo[3,4-d]pyrimidin-6-yl]propan-1-one	1979993: Inhibition of ATR (unknown origin) using peptide as substrate preincubated for 10 mins followed by substrate addition by microplate reader analysis	ic50	0.0020	uM
4-fluoro-1-[4-[(3R)-3-methylmorpholin-4-yl]-7-methylsulfonylthieno[3,2-d]pyrimidin-2-yl]benzimidazol-2-amine	1970596: Inhibition of ATR (unknown origin)	ic50	0.0020	uM
(3R)-4-[2-(benzimidazol-1-yl)-7-methylsulfonylthieno[3,2-d]pyrimidin-4-yl]-3-methylmorpholine	1970596: Inhibition of ATR (unknown origin)	ic50	0.0023	uM
(3R)-4-[2-(1H-indol-4-yl)-7-methylsulfonylpyrrolo[2,3-d]pyrimidin-4-yl]-3-methylmorpholine	2086900: Inhibition of ATR/ATRIP (unknown origin) using 5-FAM-AK-17 as substrate preincubated with compound for 10 mins followed by ATP addition and measured after 240 mins by mobility shift assay	ic50	0.0023	uM
(3R)-3-methyl-4-[2-(6-methyl-1H-indol-4-yl)-7-methylsulfonylpyrrolo[2,3-d]pyrimidin-4-yl]morpholine	2086900: Inhibition of ATR/ATRIP (unknown origin) using 5-FAM-AK-17 as substrate preincubated with compound for 10 mins followed by ATP addition and measured after 240 mins by mobility shift assay	ic50	0.0023	uM

CTD chemical–gene interactions

111 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Cisplatin	affects reaction, decreases activity, decreases response to substance, increases reaction, decreases expression (+7 more)	7
sodium arsenite	affects methylation, decreases expression	5
Caffeine	increases reaction, decreases activity, decreases phosphorylation, decreases reaction, increases activity (+4 more)	5
Tobacco Smoke Pollution	decreases expression, increases expression	5
bisphenol A	affects cotreatment, increases expression, decreases expression, decreases methylation	3
3-amino-6-(4-(methylsulfonyl)phenyl)-N-phenylpyrazine-2-carboxamide	decreases phosphorylation, decreases reaction, increases phosphorylation, affects response to substance	3
Estradiol	increases expression	3
Cadmium Chloride	increases abundance, increases phosphorylation, increases expression	3
2-chloroethyl ethyl sulfide	increases phosphorylation, affects reaction	2
chromium hexavalent ion	affects reaction, increases phosphorylation, increases ubiquitination, increases reaction, increases activity	2
4-cyclohexylmethoxy-5-nitrosopyrimidine-2,6-diamine	affects cotreatment, decreases reaction, increases phosphorylation, decreases activity, increases response to substance	2
Resveratrol	affects cotreatment, decreases reaction, increases activity, increases expression, increases phosphorylation	2
Decitabine	affects localization, increases phosphorylation, increases reaction, increases activity, affects reaction (+1 more)	2
Arsenic Trioxide	increases activity, increases expression, increases reaction	2
Acetaminophen	decreases expression, increases expression	2
Cadmium	increases abundance, increases phosphorylation	2
Camptothecin	decreases reaction, increases phosphorylation, decreases response to substance	2
Doxorubicin	affects response to substance, decreases phosphorylation, affects expression	2
Floxuridine	decreases response to substance	2
Hydroxyurea	increases response to substance, decreases reaction, increases activity, increases phosphorylation, increases reaction (+1 more)	2
Metribolone	increases phosphorylation, decreases reaction, increases expression, affects binding, increases reaction	2
FR900359	affects phosphorylation	1
prexasertib	affects response to substance, decreases phosphorylation	1
methyleugenol-2’,3’-epoxide	increases phosphorylation	1
3’-oxomethylisoeugenol	increases phosphorylation	1
PF-06840003	decreases expression, decreases reaction	1
ABBV-744	increases phosphorylation	1
INCB057643	affects cotreatment, decreases phosphorylation	1
dicrotophos	decreases expression	1
methyleugenol	increases phosphorylation	1

ChEMBL screening assays

231 unique, capped per target: 226 binding, 5 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3760509	Binding	Activation of ATM/ATR in human HCT116 cells assessed as increase in Chk1 phosphorylation at S345 at 7.5 to 30 uM after 24 hrs by Western blot analysis	Antitumor Activity of Americanin A Isolated from the Seeds of Phytolacca americana by Regulating the ATM/ATR Signaling Pathway and the Skp2-p27 Axis in Human Colon Cancer Cells. — J Nat Prod
CHEMBL4612751	Functional	In vivo inhibition of ATR in human SUDHL8 cells harboring ATM K1964E mutant xenografted CB-17 mouse assessed as reduction in ATR phosphorylation at 50 mg/kg, po bid dosed every 3 days followed by 4 days interval	Damage Incorporated: Discovery of the Potent, Highly Selective, Orally Available ATR Inhibitor BAY 1895344 with Favorable Pharmacokinetic Properties and Promising Efficacy in Monotherapy and in Combination Treatments in Preclinical Tumor Models. — J Med Chem

Cellosaurus cell lines

26 cell lines: 20 cancer cell line, 4 transformed cell line, 1 finite cell line, 1 telomerase immortalized cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_1279	HGC-27	Cancer cell line	Sex unspecified
CVCL_1508	NCI-H1944	Cancer cell line	Female
CVCL_1688	SF126	Cancer cell line	Female
CVCL_1B42	AIK-T4	Transformed cell line	Female
CVCL_2142	NK-92	Cancer cell line	Male
CVCL_2299	ATRFLOX	Cancer cell line	Male
CVCL_6G80	GM18366	Finite cell line	Male
CVCL_6G81	GM18367	Transformed cell line	Male
CVCL_7947	GM847/ATRkd	Transformed cell line	Male
CVCL_A5LZ	U2OS-ATRkd	Cancer cell line	Female

Clinical trials (associated diseases)

599 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT03144206	PHASE4	ACTIVE_NOT_RECRUITING	Hyperbaric Oxygen Therapy for Soft Tissue Sarcoma Pilot Study
NCT03244020	PHASE4	ENROLLING_BY_INVITATION	LMWH vs Aspirin for VTE Prophylaxis in Orthopaedic Oncology
NCT04033081	PHASE4	ACTIVE_NOT_RECRUITING	Registry of Sarcoma Patients Treated With Permanently Implantable LDR CivaSheet®
NCT02562170	PHASE4	COMPLETED	Protexa® Versus TiLoopBra® in Immediate Breast Reconstruction- A Pilot Study
NCT00014638	PHASE4	COMPLETED	Letrozole in Treating Postmenopausal Women With Metastatic Breast Cancer
NCT00022386	PHASE4	COMPLETED	Epoetin Alfa in Treating Chemotherapy-Related Anemia in Women With Stage I, Stage II, or Stage III Breast Cancer
NCT00029224	PHASE4	COMPLETED	Treatment With Zoledronic Acid in Patients With Breast Cancer, Multiple Myeloma, and Prostate Cancer With Cancer Related Bone Lesions
NCT00030758	PHASE4	UNKNOWN	Filgrastim or Pegfilgrastim in Preventing Neutropenia in Women Receiving Chemotherapy Following Surgery for Breast Cancer
NCT00082277	PHASE4	COMPLETED	Anastrozole Biphosphonate Study in Postmenopausal Women With Hormone-Receptor-Positive Early Breast Cancer
NCT00087620	PHASE4	TERMINATED	A Study of Capecitabine In Combination With Docetaxel vs Capecitabine Followed by Docetaxel As First-Line Treatment For Metastatic Breast Cancer
NCT00121836	PHASE4	COMPLETED	A Study of Xeloda (Capecitabine) in Women With HER2-Negative Metastatic Breast Cancer
NCT00126360	PHASE4	UNKNOWN	STARS Breast Trial (Study of Anastrozole and Radiotherapy Sequencing Pilot)
NCT00127933	PHASE4	COMPLETED	XeNA Study - A Study of Xeloda (Capecitabine) in Patients With Invasive Breast Cancer
NCT00128297	PHASE4	COMPLETED	Pamidronate Administration in Breast Cancer Patients With Bone Metastases
NCT00129597	PHASE4	UNKNOWN	Effect of Ketalar to Prevent Postoperative Chronic Pain After Mastectomy
NCT00131170	PHASE4	COMPLETED	Paravertebral Block for Breast Surgery
NCT00156039	PHASE4	COMPLETED	Randomized Trial of Follow-up Strategies in Breast Cancer
NCT00160901	PHASE4	COMPLETED	Complementary Therapies for the Reduction of Side Effects During Chemotherapy for Breast Cancer
NCT00171847	PHASE4	TERMINATED	Study of the Efficacy and Safety of Letrozole Combined With Trastuzumab in Patients With Metastatic Breast Cancer
NCT00176046	PHASE4	COMPLETED	Mistletoe Extract in Early or Advanced Breast Cancer, A Feasibility Study
NCT00190697	PHASE4	COMPLETED	A Study of LY353381 (Arzoxifene) for Patients Who Benefitted From This Drug in Other Oncology Trials and Wished to Continue Treatment
NCT00234195	PHASE4	COMPLETED	Wellbutrin XL, Major Depressive Disorder and Breast Cancer
NCT00237133	PHASE4	COMPLETED	Treatment of Locally Advanced Breast Cancer With Letrozole in Postmenopausal Women
NCT00237224	PHASE4	COMPLETED	Open Label Study of Postmenopausal Women With ER and /or PgR Positive Breast Cancer Treated With Letrozole
NCT00241046	PHASE4	TERMINATED	Letrozole in the Treatment of 1st and 2nd Line Hormone Receptor Positive Breast Cancer: Pre-therapeutic Risk Assessment
NCT00277160	PHASE4	COMPLETED	A Study of Primary Prophylaxis With Neulasta (Pegfilgrastim) Versus Secondary Prophylaxis After Chemotherapy in Elderly Subjects (>/= 65 Years Old) With Cancer
NCT00323479	PHASE4	COMPLETED	Arthralgia During Anastrozole Therapy for Breast Cancer
NCT00334139	PHASE4	COMPLETED	Effect of Zoledronic Acid on Bone Metabolism in Patients With Bone Metastasis and Prostate or Breast Cancer
NCT00356148	PHASE4	COMPLETED	The Efficacy of Prophylactic Antibiotic Administration During Breast Cancer Surgery in Overweight Patients.
NCT00372476	PHASE4	COMPLETED	Efficacy and Safety of Imatinib and Vinorelbine in Patients With Advanced Breast Cancer
NCT00413491	PHASE4	UNKNOWN	National Screening in Denmark With MR Versus Mammography and Ultrasound of Women With BRCA1 or BRCA2 Mutations
NCT00484614	PHASE4	UNKNOWN	Study the Role of Positron Emission Mammography in Pre-surgical Planning for Breast Cancer
NCT00485953	PHASE4	COMPLETED	Effect of Bisphosphonate on Bone Loss in Postmenopausal Women With Breast Cancer Initiating Aromatase Inhibitor Therapy
NCT00496678	PHASE4	COMPLETED	Trial of Patient Navigation-Activation
NCT00531973	PHASE4	UNKNOWN	A Study of Liposomal Doxorubicin in Women With Breast Cancer Exploiting Tissue Doppler Imaging
NCT00537771	PHASE4	COMPLETED	Liver Safety Under Upfront Arimidex vs Tamoxifen
NCT00544986	PHASE4	COMPLETED	A Prospective,Open-label Study of Anastrozole in Post-menopausal Women With Hormone Sensitive Advanced Breast Cancer
NCT00613275	PHASE4	COMPLETED	Patient Navigation in the Safety Net:CONNECTeDD
NCT00638599	PHASE4	COMPLETED	Comparison of Laryngeal Mask Airway (LMA®) and Tracheal Tube in Modified Radical Mastectomy on Breast Cancer
NCT00647075	PHASE4	UNKNOWN	Yunzhi as Dietary Supplement in Breast Cancer