ATRIP

Summary

ATRIP (ATR interacting protein, HGNC:33499) is a protein-coding gene on chromosome 3p21.31, encoding ATR-interacting protein (Q8WXE1). Required for checkpoint signaling after DNA damage. It is a selective cancer dependency (DepMap: 64.8% of cell lines).

This gene encodes an essential component of the DNA damage checkpoint. The encoded protein binds to single-stranded DNA coated with replication protein A. The protein also interacts with the ataxia telangiectasia and Rad3 related protein kinase, resulting in its accumulation at intranuclear foci induced by DNA damage. Multiple transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 84126 — RefSeq curated summary.

At a glance

• Gene–disease (curated): breast cancer (Moderate, GenCC) — +2 more curated relationships
• GWAS associations: 8
• Clinical variants (ClinVar): 1,829 total — 23 pathogenic, 27 likely-pathogenic (top 1% of genes corpus-wide)
• GTEx eGene: eQTL in 41 tissues, sQTL in 36 (q < 0.05)
• Phenotypes (HPO): 26
• ChEMBL bioactivity: 3 clinical-phase molecules tested; no curated mechanism-of-action drug
• Cancer dependency (DepMap): dependent in 64.8% of screened cell lines
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 0.71 (unconstrained)
• MANE Select transcript: NM_130384
• Notable: 1,829 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:33499
Approved symbol	ATRIP
Name	ATR interacting protein
Location	3p21.31
Locus type	gene with protein product
Status	Approved
Aliases	FLJ12343, MGC20625, MGC21482, MGC26740
Ensembl gene	ENSG00000164053
Ensembl biotype	protein_coding
OMIM	606605
Entrez	84126

Gene structure

Transcript identifiers

Ensembl transcripts: 20 — 10 protein_coding, 9 nonsense_mediated_decay, 1 retained_intron

MANE Select: ENST00000320211

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 3, TSL 2: 2, TSL 3: 1, TSL 4: 1, TSL 5: 2

ENST00000320211, ENST00000346691, ENST00000412052, ENST00000634384, ENST00000635082, ENST00000635084, ENST00000635099, ENST00000635464, ENST00000639561, ENST00000885532, ENST00000949796, ENST00000949797, ENST00000949798, ENST00000949799, ENST00000975466, ENST00001013425, ENST00001013426, ENST00001069393, ENST00001069394, ENST00001143945

RefSeq mRNA: 4 — MANE Select: NM_130384 NM_001271022, NM_001271023, NM_032166, NM_130384

CCDS: CCDS2767, CCDS2768, CCDS59449

Canonical transcript exons

ENST00000320211 — 13 exons

Exon	Start	End
ENSE00003815167	48450037	48450170
ENSE00003816124	48464831	48465083
ENSE00003819827	48451729	48451899
ENSE00003822754	48463745	48463881
ENSE00003824146	48454300	48454418
ENSE00003825128	48464582	48464662
ENSE00003826515	48464041	48464132
ENSE00003826701	48459359	48459454
ENSE00003826890	48460110	48460799
ENSE00003827205	48459787	48459916
ENSE00003830403	48457259	48457416
ENSE00003841907	48446737	48447092
ENSE00004803921	48465487	48467645

Expression profiles

Bgee: expression breadth ubiquitous, 170 present calls, max score 87.43.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 9.7042 / max 205.5660, expressed in 1771 samples.

Highest expression (Bgee): testis, primordial germ cell in gonad, granulocyte, ventricular zone, male germ line stem cell (sensu Vertebrata) in testis.

Genetic regulation across tissues (GTEx eQTL / sQTL)

ATRIP is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 41 tissues and its splicing (sQTL) in 36 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 77 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Skin Sun Exposed Lower leg	eqtl	5.7e-44	-0.40	3:48466268:T:C
Skin Not Sun Exposed Suprapubic	eqtl	3.7e-23	-0.38	3:48446391:G:C
Cells EBV-transformed lymphocytes	sqtl	9.7e-22	+0.91	3:48467186:T:C
Muscle Skeletal	eqtl	2.4e-21	-0.31	3:48472578:A:ATGCT
Skin Sun Exposed Lower leg	sqtl	2.2e-18	+0.49	3:48432839:G:A
Skin Not Sun Exposed Suprapubic	sqtl	5.0e-16	+0.52	3:48467186:T:C
Muscle Skeletal	sqtl	8.3e-16	+0.45	3:48467186:T:C
Cells Cultured fibroblasts	sqtl	1.8e-13	+0.55	3:48446507:A:G
Lung	sqtl	5.4e-13	+0.47	3:48467186:T:C
Esophagus Muscularis	eqtl	7.7e-13	-0.37	3:48466268:T:C
Brain Nucleus accumbens basal ganglia	eqtl	1.0e-12	-0.59	3:48446391:G:C
Artery Aorta	sqtl	1.3e-12	+0.59	3:48467186:T:C
Nerve Tibial	sqtl	1.4e-11	+0.44	3:48467186:T:C
Esophagus Mucosa	sqtl	2.2e-11	-0.50	3:48385276:A:C
Testis	eqtl	7.7e-11	-0.69	3:48436626:T:C
Brain Caudate basal ganglia	eqtl	9.0e-11	-0.55	3:48446391:G:C
Adipose Subcutaneous	eqtl	6.4e-10	-0.23	3:48446391:G:C
Adipose Visceral Omentum	eqtl	1.1e-09	-0.30	3:48466268:T:C
Artery Tibial	eqtl	1.3e-09	-0.23	3:48446391:G:C
Adipose Visceral Omentum	sqtl	3.3e-09	+0.42	3:48467186:T:C

FANTOM5 promoters

3 alternative TSS:

Promoter ID	TPM avg	Samples expressed
36577	5.3409	1562
36576	4.3395	1622
36578	0.0239	7

Top tissues by expression

showing 100 of 240 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	87.43	gold quality
right testis	UBERON:0004534	87.38	gold quality
testis	UBERON:0000473	85.44	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	84.48	gold quality
granulocyte	CL:0000094	81.56	gold quality
ventricular zone	UBERON:0003053	81.14	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	80.54	gold quality
ganglionic eminence	UBERON:0004023	80.19	gold quality
cortical plate	UBERON:0005343	79.28	gold quality
right lobe of thyroid gland	UBERON:0001119	79.24	gold quality
gastrocnemius	UBERON:0001388	79.13	gold quality
calcaneal tendon	UBERON:0003701	79.11	gold quality
muscle of leg	UBERON:0001383	78.82	gold quality
skin of leg	UBERON:0001511	78.46	gold quality
lower esophagus mucosa	UBERON:0035834	78.17	gold quality
cerebellar hemisphere	UBERON:0002245	77.91	gold quality
skin of abdomen	UBERON:0001416	77.80	gold quality
cerebellar cortex	UBERON:0002129	77.72	gold quality
apex of heart	UBERON:0002098	77.70	gold quality
right hemisphere of cerebellum	UBERON:0014890	77.63	gold quality
left lobe of thyroid gland	UBERON:0001120	77.41	gold quality
islet of Langerhans	UBERON:0000006	77.37	gold quality
popliteal artery	UBERON:0002250	77.37	gold quality
tibial artery	UBERON:0007610	77.36	gold quality
tibial nerve	UBERON:0001323	77.27	gold quality
ectocervix	UBERON:0012249	77.25	gold quality
hindlimb stylopod muscle	UBERON:0004252	77.19	gold quality
smooth muscle tissue	UBERON:0001135	76.94	gold quality
esophagus mucosa	UBERON:0002469	76.77	gold quality
right ovary	UBERON:0002118	76.73	gold quality
stromal cell of endometrium	CL:0002255	76.67	gold quality
right adrenal gland	UBERON:0001233	76.61	gold quality
lower esophagus muscularis layer	UBERON:0035833	76.46	gold quality
esophagus	UBERON:0001043	76.44	gold quality
lower esophagus	UBERON:0013473	76.44	gold quality
thyroid gland	UBERON:0002046	76.35	gold quality
left coronary artery	UBERON:0001626	76.27	gold quality
leukocyte	CL:0000738	76.13	gold quality
aorta	UBERON:0000947	76.13	gold quality
body of uterus	UBERON:0009853	76.13	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	76.03	gold quality
rectum	UBERON:0001052	76.00	gold quality
muscle layer of sigmoid colon	UBERON:0035805	75.93	gold quality
monocyte	CL:0000576	75.89	gold quality
endocervix	UBERON:0000458	75.87	gold quality
left ovary	UBERON:0002119	75.83	gold quality
cerebellum	UBERON:0002037	75.81	gold quality
left uterine tube	UBERON:0001303	75.53	gold quality
zone of skin	UBERON:0000014	75.51	gold quality
right adrenal gland cortex	UBERON:0035827	75.31	gold quality
mucosa of transverse colon	UBERON:0004991	75.24	gold quality
body of stomach	UBERON:0001161	75.20	gold quality
left adrenal gland	UBERON:0001234	75.10	gold quality
vermiform appendix	UBERON:0001154	75.06	gold quality
thoracic aorta	UBERON:0001515	74.97	gold quality
left adrenal gland cortex	UBERON:0035825	74.97	gold quality
coronary artery	UBERON:0001621	74.94	gold quality
ascending aorta	UBERON:0001496	74.92	gold quality
descending thoracic aorta	UBERON:0002345	74.75	gold quality
omental fat pad	UBERON:0010414	74.72	gold quality
peritoneum	UBERON:0002358	74.63	gold quality
right coronary artery	UBERON:0001625	74.57	gold quality
upper lobe of left lung	UBERON:0008952	74.44	gold quality
pancreas	UBERON:0001264	74.34	gold quality
adrenal tissue	UBERON:0018303	74.30	gold quality
minor salivary gland	UBERON:0001830	74.22	gold quality
body of pancreas	UBERON:0001150	74.15	gold quality
adrenal gland	UBERON:0002369	74.15	gold quality
right uterine tube	UBERON:0001302	73.92	gold quality
spleen	UBERON:0002106	73.89	gold quality
adipose tissue of abdominal region	UBERON:0007808	73.87	gold quality
right lobe of liver	UBERON:0001114	73.58	gold quality
transverse colon	UBERON:0001157	73.57	gold quality
right atrium auricular region	UBERON:0006631	73.53	gold quality
metanephros cortex	UBERON:0010533	73.51	gold quality
lymph node	UBERON:0000029	73.49	gold quality
subcutaneous adipose tissue	UBERON:0002190	73.38	gold quality
mucosa of stomach	UBERON:0001199	73.24	gold quality
heart left ventricle	UBERON:0002084	73.15	gold quality
stomach	UBERON:0000945	73.09	gold quality
right lung	UBERON:0002167	73.08	gold quality
cardiac atrium	UBERON:0002081	72.69	gold quality
adrenal cortex	UBERON:0001235	72.62	gold quality
upper lobe of lung	UBERON:0008948	72.61	gold quality
gall bladder	UBERON:0002110	72.59	gold quality
small intestine Peyer’s patch	UBERON:0003454	72.52	gold quality
ovary	UBERON:0000992	72.36	gold quality
cardiac ventricle	UBERON:0002082	72.09	gold quality
mouth mucosa	UBERON:0003729	72.04	gold quality
bone marrow cell	CL:0002092	71.96	silver quality
heart	UBERON:0000948	71.96	gold quality
tendon	UBERON:0000043	71.92	gold quality
vagina	UBERON:0000996	71.86	gold quality
blood	UBERON:0000178	71.82	gold quality
uterine cervix	UBERON:0000002	71.61	gold quality
prefrontal cortex	UBERON:0000451	71.53	gold quality
right frontal lobe	UBERON:0002810	71.25	gold quality
adenohypophysis	UBERON:0002196	71.11	gold quality
prostate gland	UBERON:0002367	71.02	gold quality
anatomical system	UBERON:0000467	70.98	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-GEOD-100618	no	187.00
E-ANND-3	no	3.08

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 80 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Testis	tissue	14.0	high
Frontal cortex	tissue	12.4
Caudate putamen	tissue	9.5
Corpus callosum	tissue	6.3
Spinal cord	tissue	5.7
Substantia nigra	tissue	5.5
Midbrain	tissue	5.4
Pons	tissue	5.3
Choroid plexus	tissue	5.3
Hypothalamus	tissue	5.2
Cerebellum	tissue	5.2	high
Medulla oblongata	tissue	5.1
Thyroid gland	tissue	5.1	high
Thalamus	tissue	5.0
Hippocampal formation	tissue	5.0
Periaqueductal gray	tissue	5.0
Cerebral cortex	tissue	4.9	high
Somatosensory cortex	tissue	4.9
Bone marrow	tissue	4.8	low
Insular cortex	tissue	4.8
Prefrontal cortex	tissue	4.7
Amygdala	tissue	4.7
Ventral forebrain	tissue	4.7
Olfactory bulb	tissue	4.7
Septum	tissue	4.7
Retrosplenial cortex	tissue	4.7
Putamen	tissue	4.6
Superior colliculi	tissue	4.6
Temporal cortex	tissue	4.6
Motor cortex	tissue	4.5
Thymus	tissue	4.5
Tonsil	tissue	4.5	medium
Entorhinal cortex	tissue	4.4
Retrosplenial and cingulate cortex	tissue	4.4
Occipital cortex	tissue	4.4
Nucleus accumbens	tissue	4.3
Hippocampus	tissue	4.3	high
Basal ganglia	tissue	4.2	high
Locus coeruleus	tissue	4.1
Postcentral gyrus	tissue	3.9
Parathyroid gland	tissue	3.8	low
Skin 1	tissue	3.7	medium
Cervix	tissue	3.6	high
Appendix	tissue	3.5	high
Lymph node	tissue	3.4	low
Seminal vesicle	tissue	3.4	medium
Esophagus	tissue	3.4	medium
Skeletal muscle	tissue	3.4	high
Lung	tissue	3.4	high
Vagina	tissue	3.2	medium
Rectum	tissue	3.2	medium
Breast	tissue	3.1	medium
Placenta	tissue	3.0	high
Endometrium 1	tissue	2.9	medium
Kidney	tissue	2.9	medium
Ovary	tissue	2.8	medium
Smooth muscle	tissue	2.8	medium
Tongue	tissue	2.8
Prostate	tissue	2.8	high
Pituitary gland	tissue	2.7

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — Flocculonodular lobe (8.3), Vermis (7.9), Cerebellar cortex (7.8), White matter (6.3), Ventral spinal cord (5.7).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): HIF1A

miRNA regulators (miRDB)

Targeting ATRIP by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

4 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4715-3P	99.98	66.03	670
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-6131	97.22	66.72	960
HSA-MIR-34A-3P	96.80	67.70	805

Functional genomics

gnomAD constraint: pLI 1.44e-06, LOEUF 0.707, missense Z 0.419 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000320211 — one region, missense o/e 0.95. DepMap (CRISPR cell-line fitness): dependent in 64.8% of screened cell lines.

Most-dependent cell lines (DepMap gene-effect, lower = stronger; ≤ −0.5 shown): SK-N-FI (-1.542), BICR 31 (-1.462), OCUM-1 (-1.395), WM-115 (-1.39), HCC1806 (-1.308), HCC1143 (-1.282), UACC-893 (-1.276), HCC38 (-1.231), Panc 03.27 (-1.21), SNU-5 (-1.185), U-BLC1 (-1.178), NCI-H2171 (-1.134), SK-N-AS (-1.127), DMS 53 (-1.106), SK-MEL-30 (-1.104).

Literature-anchored findings (GeneRIF, showing 19)

• 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)
• 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)
• Collectively, our results suggest that the ATR-mediated phosphorylation of ATRIP at Ser-68 and -72 is dispensable for the initial response to DNA damage. (PMID:15451423)
• N-terminal domain of the ATRIP protein contributes to the cell cycle checkpoint by regulating the intranuclear localization of ATR (PMID:15527801)
• ATRIP is required for ATR accumulation at intranuclear foci induced by DNA damage. (PMID:15743907)
• ATRIP oligomerization is essential for the function of the ATM and Rad3-related (ATR)-ATRIP complex, which exists in higher order oligomeric states within cells (PMID:16027118)
• The expression of dimerization-defective ATRIP diminishes the maintenance of replication forks during treatment with DNA replication inhibitors. (PMID:16176973)
• support the idea of a multistep model for ATR activation that requires separable localization and activation functions of ATRIP (PMID:17339343)
• a direct physical interaction between BRCA1 and ATRIP is required for the checkpoint function of ATR (PMID:17616665)
• ATRIP is a CDK2 substrate, and CDK2-dependent phosphorylation of S224 regulates the ability of ATR-ATRIP to promote cell cycle arrest in response to DNA damage (PMID:17638878)
• ATRIP may function outside the context of the canonical ATR damage signaling pathway during HSV-1 infection to participate in the viral life cycle. (PMID:20861269)
• our analysis exposes an overlapping clinical manifestation between the disorders but allows an expanded spectrum of clinical features for ATR-ATRIP Seckel Syndrome to be defined (PMID:23144622)
• as an ATR-associated kinase, Nek1 enhances the stability and activity of ATR-ATRIP before DNA damage, priming ATR-ATRIP for a robust DNA damage response (PMID:23345434)
• Data indicate that ATRIP is a direct target gene of HIF-1, and the increased ATRIP then activates the ATR signaling pathway under hypoxia. (PMID:23454212)
• Data on crystal structure of BRCA1 binding with phosphopeptides suggest that C-terminal domain of BRCA1 interacts with ATRIP and BAAT1 with preferences for specific side chains; in ATRIP, phospho-Ser239 and Phe242 are the main interacting residues. (PMID:24073851)
• ATRIP SUMOylation promotes ATR activation by providing a unique type of protein glue that boosts multiple protein interactions along the ATR pathway (PMID:24990965)
• ATRIP deacetylation by SIRT2 promotes ATR-ATRIP binding to replication protein A-single-stranded DNA to drive ATR activation and thus facilitate recovery from replication stress. (PMID:26854234)
• ATRIP protects progenitor cells against DNA damage in vivo. (PMID:33110058)
• Variants in ATRIP are associated with breast cancer susceptibility in the Polish population and UK Biobank. (PMID:36977412)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Atrip	ENSMUSG00000025646
rattus_norvegicus	Atrip	ENSRNOG00000020670

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1925349) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 27 distinct phenotype terms.

Mouse phenotype (MP)	Records
microphthalmia	2
preweaning lethality, complete penetrance	2
microcephaly	1
cerebellum hypoplasia	1
decreased body weight	1
abnormal retina morphology	1
abnormal lens fiber morphology	1
increased circulating chloride level	1
aphakia	1
abnormal lens epithelium morphology	1
abnormal retina layer morphology	1
abnormal mitosis	1
abnormal eye physiology	1
abnormal cell physiology	1
increased circulating sodium level	1
abnormal retina progenitor cell morphology	1
decreased visual acuity	1
retina photoreceptor degeneration	1
retina outer nuclear layer degeneration	1
increased lens epithelium apoptosis	1
decreased birth weight	1
decreased fasting circulating glucose level	1
embryonic lethality prior to organogenesis	1
decreased cerebral cortex total cell area	1
decreased dorsal striatum total cell area	1

+2 more (showing top 25).

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Macaca fascicularis	Q9N077	96.8%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
MIR711	ncRNA	100313843
ATRIP-TREX1	ncRNA	111822955
TREX1	protein-coding	11277
COL7A1	protein-coding	1294
SHISA5	protein-coding	51246
PFKFB4	protein-coding	5210
UCN2	protein-coding	90226
MIR6823	ncRNA	102465494
TMA7	protein-coding	51372
PLXNB1	protein-coding	5364
CCDC51	protein-coding	79714
FBXW12	protein-coding	285231
MIR2115	ncRNA	100313840
SPINK8	protein-coding	646424
SNORA94	snoRNA	106635528
UQCRC1	protein-coding	7384

Protein

Protein identifiers

ATR-interacting protein — Q8WXE1 (reviewed: Q8WXE1)

Alternative names: ATM and Rad3-related-interacting protein

All UniProt accessions (6): A0A0U1RQJ8, A0A0U1RQR9, A0A0U1RQW3, A0A0U1RRM7, A0A1W2PQ89, Q8WXE1

UniProt curated annotations — full annotation on UniProt →

Function. Required for checkpoint signaling after DNA damage. Required for ATR expression, possibly by stabilizing the protein.

Subunit / interactions. Interacts with ATR. Heterodimer with ATR. The heterodimer binds the RPA complex and is then recruited to single-stranded DNA. Interacts with CEP164 (via N-terminus). Interacts with CINP.

Subcellular location. Nucleus.

Tissue specificity. Ubiquitous.

Post-translational modifications. Phosphorylated by ATR.

Domain organisation. The EEXXXDDL motif is required for the interaction with catalytic subunit PRKDC and its recruitment to sites of DNA damage.

Similarity. Belongs to the ATRIP family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q8WXE1-1	1	yes
Q8WXE1-2	2
Q8WXE1-3	3
Q8WXE1-5	4

RefSeq proteins (4): NP_001257951, NP_001257952, NP_115542, NP_569055* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR033349	ATRIP	Family
IPR060331	ATRIP_N	Domain
IPR060332	ATRIP_C	Domain

Pfam: PF28409, PF28426

UniProt features (24 total): sequence conflict 8, splice variant 3, region of interest 2, sequence variant 2, mutagenesis site 2, helix 2, compositionally biased region 2, chain 1, coiled-coil region 1, short sequence motif 1

Structure

Experimental structures (PDB)

24 structures by resolution:

PDB	Title	Method	Resolution (Å)
4NB3	Crystal structure of RPA70N in complex with a 3,4 dichlorophenylalanine ATRIP derived …	X-RAY DIFFRACTION	1.35
7XV4	Crystal structure of RPA70N-ATRIP fusion	X-RAY DIFFRACTION	1.6
4IGK	Structure of human BRCA1 BRCT in complex with ATRIP peptide	X-RAY DIFFRACTION	1.75
9ZCY	Cryo-EM structure of apo-ATR-ATRIP	ELECTRON MICROSCOPY	2.5
23EW	Cryo-EM structure of human ATR-ATRIP complex with Berzosertib	ELECTRON MICROSCOPY	2.7
23FC	Cryo-EM structure of human ATR-ATRIP complex with ATPgammaS and Chk1	ELECTRON MICROSCOPY	2.7
13DE	Cryo-EM structure of ATR-ATRIP-ETAA1 AAD (S95D/S111D)	ELECTRON MICROSCOPY	2.9
23FE	Cryo-EM structure of human ATR-ATRIP complex with ATPgammaS, Chk1 and ETAA1	ELECTRON MICROSCOPY	2.9
23FB	Cryo-EM structure of human ATR-ATRIP complex with ATPgammaS	ELECTRON MICROSCOPY	3
9ZD3	Cryo-EM structure of ATR-ATRIP-ETAA1 AAD	ELECTRON MICROSCOPY	3
23FA	Cryo-EM structure of human ATR-ATRIP complex with Gartisertib	ELECTRON MICROSCOPY	3.1
23EX	Cryo-EM structure of human ATR-ATRIP complex with Ceralasertib	ELECTRON MICROSCOPY	3.2
23EY	Cryo-EM structure of human ATR-ATRIP complex with Elimusertib	ELECTRON MICROSCOPY	3.2
9ZD1	Cryo-EM structure of ATR-ATRIP-TOPBP1 AAD	ELECTRON MICROSCOPY	3.2
9ZD4	Cryo-EM structure of symmetric class of ATR-ATRIP-ETAA1 AAD	ELECTRON MICROSCOPY	3.3
26ZN	Cryo-EM structure of human phosphorylate ATR-ATRIP complex with ATPgammaS	ELECTRON MICROSCOPY	3.5
23FD	Cryo-EM structure of human ATR-ATRIP complex with ATPgammaS, Chk1 and TopBp1	ELECTRON MICROSCOPY	3.6
9L4D	ATR-ATRIP bound with RP-3500	ELECTRON MICROSCOPY	3.79
9L43	ATR Spiral -ATRIP bound with VE-822	ELECTRON MICROSCOPY	3.83
9L45	ATR-ATRIP bound with VE-822	ELECTRON MICROSCOPY	3.95
9L4C	ATR Spiral -ATRIP bound with RP-3500	ELECTRON MICROSCOPY	4.06
5YZ0	Cryo-EM Structure of human ATR-ATRIP complex	ELECTRON MICROSCOPY	4.7
9L4F	ATR-ATRIP bound with ATPgammaS	ELECTRON MICROSCOPY	6.22
9L46	ATR-ATRIP-bound with AMP-PNP	ELECTRON MICROSCOPY	6.29

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8WXE1-F1	70.10	0.35

Human Protein Atlas

Protein class: Predicted intracellular proteins, Essential proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): nucleoplasm

Antibody reliability (HPA): IH approved · IF supported

Functional residue map

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

Mutagenesis-validated functional residues (2)

Position	Phenotype
769–770	abolishes interaction with atr and its recruitment to sites of dna damage.
774–775	abolishes interaction with atr and its recruitment to sites of dna damage.

Function

Pathways and Gene Ontology

Reactome pathways

8 curated (TAS) of 26; 5 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

26 pathways:

ID	Pathway	Evidence
R-HSA-9709570	Impaired BRCA2 binding to RAD51 ⚕	curated
R-HSA-176187	Activation of ATR in response to replication stress	curated
R-HSA-6783310	Fanconi Anemia Pathway	curated
R-HSA-69473	G2/M DNA damage checkpoint	curated
R-HSA-5685938	HDR through Single Strand Annealing (SSA)	curated
R-HSA-5693616	Presynaptic phase of homologous DNA pairing and strand exchange	curated
R-HSA-5693607	Processing of DNA double-strand break ends	curated
R-HSA-6804756	Regulation of TP53 Activity through Phosphorylation	curated
R-HSA-9701190	Defective homologous recombination repair (HRR) due to BRCA2 loss of function ⚕	—
R-HSA-1643685	Disease ⚕	—
R-HSA-9675136	Diseases of DNA Double-Strand Break Repair ⚕	—
R-HSA-9675135	Diseases of DNA repair ⚕	—
R-HSA-1640170	Cell Cycle	—
R-HSA-69620	Cell Cycle Checkpoints	—
R-HSA-5693532	DNA Double-Strand Break Repair	—
R-HSA-73894	DNA Repair	—
R-HSA-69481	G2/M Checkpoints	—
R-HSA-74160	Gene expression (Transcription)	—
R-HSA-212436	Generic Transcription Pathway	—
R-HSA-5685942	HDR through Homologous Recombination (HRR)	—
R-HSA-5693567	HDR through Homologous Recombination (HRR) or Single Strand Annealing (SSA)	—
R-HSA-5693579	Homologous DNA Pairing and Strand Exchange	—
R-HSA-5693538	Homology Directed Repair	—
R-HSA-73857	RNA Polymerase II Transcription	—
R-HSA-5633007	Regulation of TP53 Activity	—
R-HSA-3700989	Transcriptional Regulation by TP53	—

MSigDB gene sets: 145 (showing top): PID_FANCONI_PATHWAY, GOBP_REGULATION_OF_DOUBLE_STRAND_BREAK_REPAIR, REACTOME_G2_M_DNA_DAMAGE_CHECKPOINT, GOBP_CELL_CYCLE_PHASE_TRANSITION, REACTOME_ACTIVATION_OF_ATR_IN_RESPONSE_TO_REPLICATION_STRESS, GOBP_REGULATION_OF_DNA_REPAIR, GOBP_NEGATIVE_REGULATION_OF_CELL_CYCLE_PROCESS, GOBP_NEGATIVE_REGULATION_OF_CELL_CYCLE, GOBP_REGULATION_OF_CELL_CYCLE, GOBP_REGULATION_OF_RESPONSE_TO_STRESS, GOBP_DNA_DAMAGE_RESPONSE, LASTOWSKA_NEUROBLASTOMA_COPY_NUMBER_DN, GOBP_SIGNAL_TRANSDUCTION_IN_RESPONSE_TO_DNA_DAMAGE, GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_STRESS, GOBP_CELL_CYCLE_CHECKPOINT_SIGNALING

GO Biological Process (5): DNA damage checkpoint signaling (GO:0000077), nucleobase-containing compound metabolic process (GO:0006139), DNA repair (GO:0006281), regulation of double-strand break repair (GO:2000779), DNA damage response (GO:0006974)

GO Molecular Function (3): K63-linked polyubiquitin modification-dependent protein binding (GO:0070530), exonuclease activity (GO:0004527), protein binding (GO:0005515)

GO Cellular Component (2): nucleus (GO:0005634), nucleoplasm (GO:0005654)

Reactome top-level categories

14 top-level categories:

Category	Pathways
HDR through Homologous Recombination (HRR) or Single Strand Annealing (SSA)	3
G2/M Checkpoints	2
DNA Repair	2
Homologous DNA Pairing and Strand Exchange	1
Regulation of TP53 Activity	1
Defective homologous recombination repair (HRR) due to BRCA2 loss of function	1
RNA Polymerase II Transcription	1
Generic Transcription Pathway	1
Transcriptional Regulation by TP53	1
DNA Double-Strand Break Repair	1
Homology Directed Repair	1
HDR through Homologous Recombination (HRR)	1
Cell Cycle Checkpoints	1
Cell Cycle	1

GO top-level categories

15 GO namespaces:

Category	Terms
DNA integrity checkpoint signaling	1
signal transduction in response to DNA damage	1
primary metabolic process	1
DNA metabolic process	1
DNA damage response	1
regulation of DNA repair	1
double-strand break repair	1
cellular response to stress	1
polyubiquitin modification-dependent protein binding	1
nuclease activity	1
hydrolase activity, acting on ester bonds	1
binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cellular anatomical structure	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 2 of 10 annotations. The rest are phylogenetic / computational / electronic (IEA).

2 experimentally-supported GO terms:

GO term	NS	Evidence
nucleoplasm	CC	direct assay
K63-linked polyubiquitin modification-dependent protein binding	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 1,186 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ATRIP	RAD17	O75943	944
ATRIP	CHEK1	O14757	923
ATRIP	TOPBP1	Q92547	906
ATRIP	RAD9A	Q99638	896
ATRIP	HUS1	O60921	894
ATRIP	ATR	Q13535	869
ATRIP	ATM	Q13315	857
ATRIP	PRKDC	P78527	852
ATRIP	XRCC5	P13010	834
ATRIP	RPA1	P27694	795
ATRIP	RPA2	P15927	770
ATRIP	CLSPN	Q9HAW4	766
ATRIP	ETAA1	Q9NY74	751
ATRIP	RAD50	Q92878	748
ATRIP	MDC1	Q14676	743

IntAct

Human interaction partners of ATRIP in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

27 partners by confidence:

Partner	Interaction type	MIscore	Records
ATR	direct interaction	0.890	6
CINP	physical association	0.730	8
C1orf94	physical association	0.560	3
CCDC28B	physical association	0.560	3
CDC23	physical association	0.560	3
FAM156B	physical association	0.560	3
LNX1	physical association	0.560	3
METTL21A	physical association	0.560	3
MID2	physical association	0.560	3
MOS	physical association	0.560	3
MX2	physical association	0.560	3
PCTK1	physical association	0.560	3
POLR1C	physical association	0.560	3
SCG2	physical association	0.560	3
SPRY2	physical association	0.560	3
TASOR2	physical association	0.560	3
CDK9	physical association	0.560	1
IFT20	physical association	0.550	1
CENPF	physical association	0.500	1
IKBKG	physical association	0.400	1
RRM2B	physical association	0.400	1
RIBC2	physical association	0.370	1
AURKA	association	0.350	1
HMGN1	association	0.350	1
CHEK1	colocalization	0.270	1
DBP	colocalization	0.270	1
TOPBP1	colocalization	0.270	1

BioGRID (230 interactions; top human partners by supporting records): ATR (Affinity Capture-MS; 45 records), RPA1 (Reconstituted Complex; 22 records), RPA2 (Reconstituted Complex; 7 records), TOPBP1 (Reconstituted Complex; 5 records), BRCA1 (Proximity Label-MS; 4 records), CINP (Two-hybrid; 4 records), CEP164 (Affinity Capture-Western; 3 records), ETAA1 (Affinity Capture-MS; 3 records), FANCL (Two-hybrid; 3 records), MAD2L2 (Affinity Capture-Western; 3 records), MCM2 (Affinity Capture-Western; 3 records), NBN (Affinity Capture-Western; 3 records), RPA3 (Reconstituted Complex; 3 records), SIRT2 (Affinity Capture-Western; 3 records), ZBTB14 (Affinity Capture-Western; 3 records)

SIGNOR signaling

showing 6 of 7 signaling interactions:

A	Effect	B	Mechanism
ATR	up-regulates	ATRIP	phosphorylation
CDK2	up-regulates	ATRIP	phosphorylation
CDK2	unknown	ATRIP	phosphorylation
RPA2	up-regulates	ATRIP	binding
TOPBP1	up-regulates	ATRIP	binding
NEK1	“up-regulates activity”	ATRIP	binding

Protein complexes (CORUM) (2)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

2 complexes by size:

Complex	Subunits	Members
ATR-ATRIP-TIM complex	3	ATR, ATRIP, TIMELESS
ATR-ATRIP complex	2	ATR, ATRIP

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 27 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.

GO biological processes:

GO term	Partners	Fold	FDR
DNA repair	6	16.0×	4e-04

Disease & clinical

Genetic variants

Variant evidence for ATRIP: 1,829 ClinVar records (50 pathogenic / likely pathogenic); 8 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

1,829 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	23
Likely pathogenic	27
Uncertain significance	1132
Likely benign	537
Benign	22

Top pathogenic / likely-pathogenic (15)

Showing the 15 best-reviewed of 50 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
4185	NM_033629.6(TREX1):c.52G>A (p.Asp18Asn)	Pathogenic	criteria provided, multiple submitters, no conflicts	6
449514	NM_033629.6(TREX1):c.703dup (p.Val235fs)	Pathogenic	criteria provided, multiple submitters, no conflicts	4
4181	NM_033629.6(TREX1):c.599_601dup (p.Asp200dup)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	6
4183	NM_033629.6(TREX1):c.375dup (p.Gly126fs)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	3
1711574	NM_033629.6(TREX1):c.541_544dup (p.Ile182fs)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	3
4855591	NM_033629.6(TREX1):c.598G>C (p.Asp200His)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	2
4182	NM_033629.6(TREX1):c.602T>A (p.Val201Asp)	Pathogenic	criteria provided, single submitter	3
4184	NM_033629.6(TREX1):c.598G>A (p.Asp200Asn)	Pathogenic	criteria provided, single submitter	3
126386	NM_033629.6(TREX1):c.366_368dup (p.Ala123_His124insAla)	Pathogenic	criteria provided, single submitter	2
369666	NM_033629.6(TREX1):c.629G>A (p.Trp210Ter)	Pathogenic	criteria provided, single submitter	1
1455316	NM_033629.6(TREX1):c.5del (p.Gly2fs)	Pathogenic	criteria provided, single submitter	1
1457024	NM_033629.6(TREX1):c.399dup (p.Leu134fs)	Pathogenic	criteria provided, single submitter	1
1458091	NM_033629.6(TREX1):c.357G>A (p.Trp119Ter)	Pathogenic	criteria provided, single submitter	1
2127740	NM_033629.6(TREX1):c.18dup (p.Pro7fs)	Pathogenic	criteria provided, single submitter	1
2930302	NM_033629.6(TREX1):c.226_233dup (p.Ser78fs)	Pathogenic	criteria provided, single submitter	1

Per-variant reference — Sugi Variant

Explore ATRIP’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 43 predictions of 1,313):

Position(s)	Effect	Δscore	Sites
3:48451727–48451728	acceptor_loss	1.0000	4
3:48451880	donor_gain	1.0000
3:48451900–48451901	donor_loss	1.0000	5
3:48454298–48454299	acceptor_loss	1.0000	6
3:48454419–48454420	donor_loss	1.0000	4
3:48463743–48463744	acceptor_loss	1.0000	6
3:48463882–48463883	donor_loss	1.0000	4
3:48464039–48464040	acceptor_loss	1.0000	5
3:48464133–48464134	donor_loss	1.0000	4
3:48464829–48464830	acceptor_loss	1.0000	4

AlphaMissense

832 missense substitutions predicted likely pathogenic (of 5,124 scored), across 279 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
F194	8	0.934	0.997
F253	8	0.881	0.985
D734	8	0.850	0.953
D64	8	0.844	0.929
D59	8	0.807	0.905
H746	8	0.791	0.917
F737	7	0.946	0.973
W698	7	0.934	0.988
C682	7	0.901	0.961
F247	7	0.895	0.978
E769	7	0.889	0.960
E141	7	0.870	0.949
F181	7	0.857	0.963
C680	7	0.856	0.917
H695	7	0.852	0.955
C630	7	0.839	0.934
F49	7	0.831	0.948
E198	7	0.830	0.914
F55	7	0.818	0.966
E656	7	0.811	0.938

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

2 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	6.03e-05
Liver Hepatocellular Carcinoma (validation)	unfavorable	7.15e-05

Disease associations

OMIM: gene MIM:606605 | disease phenotypes: MIM:192315, MIM:225750, MIM:610448, MIM:152700, MIM:601744, MIM:125310

GenCC curated gene-disease

2 curated gene-disease records:

Disease	Classification	Inheritance	Records
breast cancer	Moderate	Autosomal dominant
Seckel syndrome	Supportive	Autosomal recessive	2

ClinGen Gene-Disease Validity

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

1 validity classifications:

Disease	Classification	Inheritance
hereditary breast carcinoma	Limited	AD

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (2 panels, 0 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

2 panels:

Panel	Rating
Breast cancer pertinent cancer susceptibility	amber
Familial breast cancer	amber

Mondo (11): retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (MONDO:0008641), Aicardi-Goutieres syndrome 1 (MONDO:0009165), chilblain lupus 1 (MONDO:0012500), systemic lupus erythematosus (MONDO:0007915), Aicardi-Goutieres syndrome (MONDO:0018866), thrombotic microangiopathy (MONDO:0019737), inherited retinal dystrophy (MONDO:0019118), chilblain lupus (MONDO:0019557), cerebral arteriopathy with subcortical infarcts and leukoencephalopathy (MONDO:0007432), Seckel syndrome (MONDO:0019342), breast cancer (MONDO:0007254)

Orphanet (9): Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (Orphanet:247691), Cerebroretinal vasculopathy (Orphanet:3421), Aicardi-Goutières syndrome (Orphanet:51), HERNS syndrome (Orphanet:63261), Hereditary vascular retinopathy (Orphanet:71291), Systemic lupus erythematosus (Orphanet:536), Thrombotic microangiopathy (Orphanet:93573), OBSOLETE: Inherited retinal disorder (Orphanet:71862), Chilblain lupus (Orphanet:90280)

HPO phenotypes

26 phenotypes (HPO-id order):

HPO	Term
HP:0000252	Microcephaly
HP:0000275	Narrow face
HP:0000347	Micrognathia
HP:0000363	Abnormal earlobe morphology
HP:0000387	Absent earlobe
HP:0000444	Convex nasal ridge
HP:0000494	Downslanted palpebral fissures
HP:0000501	Glaucoma
HP:0000682	Abnormal dental enamel morphology
HP:0001249	Intellectual disability
HP:0001363	Craniosynostosis
HP:0001382	Joint hypermobility
HP:0001385	Hip dysplasia
HP:0001511	Intrauterine growth retardation
HP:0001852	Sandal gap
HP:0002209	Sparse scalp hair
HP:0002650	Scoliosis
HP:0002750	Delayed skeletal maturation
HP:0004209	Clinodactyly of the 5th finger
HP:0004322	Short stature
HP:0004326	Cachexia
HP:0007495	Prematurely aged appearance
HP:0009804	Tooth agenesis
HP:0010579	Cone-shaped epiphysis
HP:0011342	Mild global developmental delay
HP:0100543	Cognitive impairment

GWAS associations

8 associations:

Study	Trait	p-value
GCST004131_23	Inflammatory bowel disease	1e-33
GCST010698_7	Subcortical volume (min-P)	3e-24
GCST004132_111	Crohn’s disease	3e-23
GCST004133_74	Ulcerative colitis	8e-20
GCST010701_11	Cortical surface area (MOSTest)	1e-16
GCST010703_214	Brain morphology (MOSTest)	2e-13
GCST010702_18	Subcortical volume (MOSTest)	1e-10
GCST010699_3	Brain morphology (min-P)	4e-8

EFO canonical traits (from GWAS)

1 canonical traits:

EFO ID	Trait name
EFO:0004346	neuroimaging measurement

MeSH disease descriptors

5 disease descriptors:

Descriptor	Name	Tree numbers
D008180	Lupus Erythematosus, Systemic	C17.300.480; C20.111.590
D058499	Retinal Dystrophies	C11.768.585.658
D057049	Thrombotic Microangiopathies	C15.378.140.855.925; C15.378.243.937.925
C535607	Aicardi-Goutieres syndrome *(supp.)*
C566007	Vasculopathy, Retinal, With Cerebral Leukodystrophy *(supp.)*

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL4106138 (PROTEIN COMPLEX), CHEMBL6066578 (PROTEIN COMPLEX)

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 2,428 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

3 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL4285417	CERALASERTIB	3	1,563
CHEMBL4647810	ELIMUSERTIB	1	316
CHEMBL4650286	M4344	1	549

PharmGKB: 1 entry (CPIC guideline: no)

Binding affinities (BindingDB)

957 measured of 991 human assays (992 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
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
cyclopropyl-methyl-[2-(2-methylbenzimidazol-1-yl)-6-[(3R)-3-methylmorpholin-4-yl]pyrimidin-4-yl]imino-oxo-lambda6-sulfane	IC50	0.4 nM	US-11434233: 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
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
methyl-[2-(2-methylbenzimidazol-1-yl)-6-[(3R)-3-methylmorpholin-4-yl]pyrimidin-4-yl]imino-(oxetan-3-yl)-oxo-lambda6-sulfane	IC50	0.8 nM	US-11434233: 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
(R)-((6-(2-Amino-1H- benzo[d]imidazol-1-yl)-4-(3- methylmorpholino)pyridin-2- yl)imino)dimethyl-lambda6-sulfanone	IC50	1 nM	US-10894052: Heterocyclic inhibitors of ATR kinase
(R)-Dimethyl((6-(2-(methylamino)- 1H-benzo[d]imidazol-1-yl)-4-(3- methylmorpholino)pyridin-2- yl)imino)-lambda6-sulfanone	IC50	1 nM	US-10894052: Heterocyclic inhibitors of ATR kinase
CHEMBL4293269	IC50	1 nM
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
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
[2-(benzimidazol-1-yl)-6-[(3R)-3-methylmorpholin-4-yl]pyrimidin-4-yl]imino-methyl-(oxetan-3-yl)-oxo-lambda6-sulfane	IC50	1.4 nM	US-11434233: Heterocyclic inhibitors of ATR kinase
(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

ChEMBL bioactivities

1379 potent at pChembl≥5 of 1388 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.52	IC50	0.3	nM	CHEMBL5783158
9.40	IC50	0.4	nM	CHEMBL5786594
9.40	IC50	0.4	nM	CHEMBL6010318
9.30	IC50	0.5	nM	CHEMBL5775367
9.15	IC50	0.7	nM	CHEMBL5800832
9.10	IC50	0.8	nM	CHEMBL5783158
9.10	IC50	0.8	nM	CHEMBL5800499
9.05	IC50	0.9	nM	CHEMBL5761609
9.05	IC50	0.9	nM	CHEMBL5928836
9.00	IC50	1	nM	CHEMBL4293269
9.00	IC50	1	nM	CHEMBL5790125
9.00	IC50	1	nM	CHEMBL5957036
8.85	IC50	1.4	nM	CHEMBL5800832
8.80	IC50	1.6	nM	CHEMBL5549943
8.80	IC50	1.6	nM	CHEMBL5561233
8.80	IC50	1.6	nM	CHEMBL5784938
8.70	IC50	2	nM	CHEMBL5959731
8.70	IC50	2	nM	CHEMBL5965790
8.70	IC50	2	nM	CHEMBL5855070
8.70	IC50	2	nM	CHEMBL5875781
8.70	IC50	2	nM	CHEMBL5984958
8.70	IC50	2	nM	CHEMBL6055334
8.70	IC50	2	nM	CHEMBL6046072
8.64	IC50	2.3	nM	CHEMBL5560098
8.64	IC50	2.3	nM	CHEMBL5550050
8.52	IC50	3	nM	CHEMBL5193835
8.52	IC50	3	nM	CHEMBL6036789
8.52	IC50	3	nM	CHEMBL5774856
8.52	IC50	3	nM	CHEMBL5866351
8.52	IC50	3	nM	CHEMBL5755880
8.52	IC50	3	nM	CHEMBL5744032
8.52	IC50	3	nM	CHEMBL5900697
8.52	IC50	3	nM	CHEMBL5932571
8.52	IC50	3	nM	CHEMBL6017748
8.52	IC50	3	nM	CHEMBL5752723
8.52	IC50	3	nM	CHEMBL6023105
8.52	IC50	3	nM	CHEMBL5786271
8.52	IC50	3	nM	CHEMBL5962731
8.48	IC50	3.3	nM	CHEMBL5567922
8.42	IC50	3.8	nM	CHEMBL5566930
8.40	IC50	4	nM	CHEMBL5171719
8.40	IC50	4	nM	CHEMBL6012109
8.40	IC50	4	nM	CHEMBL5910491
8.40	IC50	4	nM	CHEMBL5739728
8.40	IC50	4	nM	CHEMBL5945434
8.40	IC50	4	nM	CHEMBL5988732
8.40	IC50	4	nM	CHEMBL5743285
8.40	IC50	4	nM	CHEMBL5885586
8.39	IC50	4.06	nM	CHEMBL6005320
8.37	IC50	4.3	nM	CHEMBL5563958

PubChem BioAssay actives

82 with measured affinity, of 103 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
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
3-[3-[4-(methylaminomethyl)phenyl]-1,2-oxazol-5-yl]-5-(4-propan-2-ylsulfonylphenyl)pyrazin-2-amine	2067682: Inhibition of human ATR/ATRIP using GST-tagged p53 as substrate in presence of 3 uM ATP by AlphaScreen assay	ic50	0.0010	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
(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
2-methyl-2-[5-[(3R)-3-methylmorpholin-4-yl]-3-(1H-pyrazol-5-yl)-2H-pyrazolo[4,3-d]pyrimidin-7-yl]propanenitrile	1872224: Inhibition of human FLAG-tagged ATR/c-Myc-tagged ATRIP expressed in mammalian expression system using p53 as substrate incubated for 2 hrs by fluorescence based assay	ic50	0.0030	uM
N-cyclopropyl-N-[2-(1H-indol-4-yl)-6-[(3R)-3-methylmorpholin-4-yl]pyrimidin-4-yl]methanesulfonamide	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	0.0033	uM
(3R)-4-[7-cyclopropylsulfonyl-2-(1H-indol-4-yl)pyrrolo[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	0.0038	uM
imino-methyl-[1-[(10S,14R)-14-methyl-4-(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]cyclopropyl]-oxo-lambda6-sulfane	1872224: Inhibition of human FLAG-tagged ATR/c-Myc-tagged ATRIP expressed in mammalian expression system using p53 as substrate incubated for 2 hrs by fluorescence based assay	ic50	0.0040	uM
(3R)-4-[7-ethylsulfonyl-2-(1H-indol-4-yl)pyrrolo[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	0.0043	uM
(3R)-4-[2-(6-chloro-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	0.0044	uM
(3R)-4-[2-(1H-indol-4-yl)-6-(1-methylsulfonylcyclopropyl)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	0.0045	uM
(3R)-4-[2-(6-methoxy-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	0.0053	uM
2-(1H-indol-4-yl)-N,N-dimethyl-4-[(3R)-3-methylmorpholin-4-yl]pyrrolo[2,3-d]pyrimidine-7-sulfonamide	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	0.0053	uM
(3R)-4-[6-(1H-indol-4-yl)-1-methylsulfonylpyrazolo[5,4-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	0.0058	uM
(3R)-3-methyl-4-[4-(2-methylpyrazol-3-yl)-8-(1H-pyrazol-5-yl)-1,7-naphthyridin-2-yl]morpholine	1743706: Displacement of 5-TAMRA-labelled Tracer A from human GST-fused/FLAG-tagged full length ATR/human N-terminal FLAG-tagged full length ATRIP expressed in HEK293-6E cells incubated for 15 mins by TR-FRET based competition binding assay	ic50	0.0070	uM
(3R)-3-methyl-4-[4-(1-methylsulfonylcyclopropyl)-1-(1H-pyrazol-5-yl)pyrazolo[5,4-b]pyridin-6-yl]morpholine	2067682: Inhibition of human ATR/ATRIP using GST-tagged p53 as substrate in presence of 3 uM ATP by AlphaScreen assay	ic50	0.0070	uM
N-[2-(1H-indol-4-yl)-6-[(3R)-3-methylmorpholin-4-yl]pyrimidin-4-yl]-N-propan-2-ylmethanesulfonamide	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	0.0078	uM
2-[2-(1H-indol-4-yl)-6-[(3R)-3-methylmorpholin-4-yl]pyrimidin-4-yl]thiane 1,1-dioxide	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	0.0078	uM
(3R)-4-[2-(1H-indol-4-yl)-7-propan-2-ylsulfonylpyrrolo[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	0.0080	uM
(3R)-3-methyl-4-[7-methylsulfonyl-2-[6-(trifluoromethyl)-1H-indol-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	0.0092	uM
4-[4-[(3R)-3-methylmorpholin-4-yl]-7-methylsulfonylpyrrolo[2,3-d]pyrimidin-2-yl]-1H-indole-6-carbonitrile	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	0.0094	uM
2-[2-(1H-indol-4-yl)-6-[(3R)-3-methylmorpholin-4-yl]pyrimidin-4-yl]thiolane 1,1-dioxide	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	0.0094	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]imidazol-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	0.0100	uM
(10S,14R)-N,14-dimethyl-6-(2-methylsulfonylpropan-2-yl)-N-(1H-pyrazol-5-yl)-8,12-dioxa-1,3,5-triazatricyclo[8.4.0.02,7]tetradeca-2,4,6-trien-4-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	0.0100	uM
1-[(10S,14R)-14-methyl-4-(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]cyclopropane-1-carbonitrile	1872224: Inhibition of human FLAG-tagged ATR/c-Myc-tagged ATRIP expressed in mammalian expression system using p53 as substrate incubated for 2 hrs by fluorescence based assay	ic50	0.0100	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	2067682: Inhibition of human ATR/ATRIP using GST-tagged p53 as substrate in presence of 3 uM ATP by AlphaScreen assay	ic50	0.0140	uM
(3R)-3-methyl-4-[1-methyl-7-(2-methylpyrazol-3-yl)-3-(1H-pyrazol-5-yl)pyrazolo[4,5-d]pyrimidin-5-yl]morpholine	1872224: Inhibition of human FLAG-tagged ATR/c-Myc-tagged ATRIP expressed in mammalian expression system using p53 as substrate incubated for 2 hrs by fluorescence based assay	ic50	0.0150	uM
(3R)-4-[2-(1-benzothiophen-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	0.0280	uM
2-(1H-indol-4-yl)-4-[(3R)-3-methylmorpholin-4-yl]-5,7-dihydrothieno[3,4-d]pyrimidine 6,6-dioxide	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	0.0321	uM
(3R)-3-methyl-4-(7-methylsulfonyl-2-naphthalen-1-ylpyrrolo[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	0.0395	uM
(3R)-3-methyl-4-[4-(1-methylsulfonylcyclopropyl)-1-(1H-pyrazol-5-yl)pyrrolo[2,3-b]pyridin-6-yl]morpholine	2067682: Inhibition of human ATR/ATRIP using GST-tagged p53 as substrate in presence of 3 uM ATP by AlphaScreen assay	ic50	0.0400	uM
2-[2-(1H-indol-4-yl)-6-[(3R)-3-methylmorpholin-4-yl]pyrimidin-4-yl]-1,2-thiazolidine 1,1-dioxide	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	0.0435	uM
(3R)-4-(2-isoquinolin-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	0.0469	uM
(3R)-4-[2-(1H-indol-5-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	0.0531	uM
4-[6-[(3R)-3-methylmorpholin-4-yl]-1-methylsulfonyl-8-oxa-3,5-diazatricyclo[7.1.1.02,7]undeca-2(7),3,5-trien-4-yl]-1H-pyrrolo[2,3-c]pyridin-5-amine	1872226: Inhibition of full-length human recombinant FLAG-tagged ATR/c-Myc-tagged ATRIP using p53 as substrate incubated for 30 mins in presence of ATP by HTRF assay	ic50	0.0621	uM
(3R)-4-[2-(1H-indol-4-yl)-7-thiophen-2-ylsulfonylpyrrolo[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	0.0849	uM
8-[5-(difluoromethyl)-3-pyridinyl]-3-methyl-1-(oxan-4-yl)pyrazolo[3,4-c]quinoline	1779777: Displacement of 5-TAMRA-labelled Tracer A from human GST-fused/FLAG-tagged full length ATR/human N-terminal FLAG-tagged full length ATRIP expressed in HEK293-6E cells preincubated for 15 mins followed by tracer A addition and measured after 30 mins by TR-FRET based competition binding assay	ic50	0.0900	uM
4-[(3R)-3-methylmorpholin-4-yl]-6-(1-methylsulfonylcyclopropyl)-N-(1H-pyrazol-5-yl)pyrimidin-2-amine	2067682: Inhibition of human ATR/ATRIP using GST-tagged p53 as substrate in presence of 3 uM ATP by AlphaScreen assay	ic50	0.1000	uM
6-[(3R)-3-methylmorpholin-4-yl]-1-methylsulfonyl-4-(1H-pyrrolo[2,3-d]pyridazin-4-yl)-8-oxa-3,5-diazatricyclo[7.1.1.02,7]undeca-2(7),3,5-triene	1872226: Inhibition of full-length human recombinant FLAG-tagged ATR/c-Myc-tagged ATRIP using p53 as substrate incubated for 30 mins in presence of ATP by HTRF assay	ic50	0.1039	uM
[3-[1-(oxan-4-yl)-[1,2,4]triazolo[4,3-a]quinoxalin-8-yl]phenyl]methanol	1779777: Displacement of 5-TAMRA-labelled Tracer A from human GST-fused/FLAG-tagged full length ATR/human N-terminal FLAG-tagged full length ATRIP expressed in HEK293-6E cells preincubated for 15 mins followed by tracer A addition and measured after 30 mins by TR-FRET based competition binding assay	ic50	0.1170	uM
1-(cyclohepten-1-yl)-8-[5-(difluoromethyl)-3-pyridinyl]-[1,2,4]triazolo[4,3-a]quinoxaline	1779777: Displacement of 5-TAMRA-labelled Tracer A from human GST-fused/FLAG-tagged full length ATR/human N-terminal FLAG-tagged full length ATRIP expressed in HEK293-6E cells preincubated for 15 mins followed by tracer A addition and measured after 30 mins by TR-FRET based competition binding assay	ic50	0.1410	uM
(3R)-3-methyl-4-[6-(1-methylsulfonylcyclopropyl)-2-(1H-pyrazol-5-ylsulfonyl)pyrimidin-4-yl]morpholine	2067682: Inhibition of human ATR/ATRIP using GST-tagged p53 as substrate in presence of 3 uM ATP by AlphaScreen assay	ic50	0.1600	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	2067682: Inhibition of human ATR/ATRIP using GST-tagged p53 as substrate in presence of 3 uM ATP by AlphaScreen assay	ic50	0.1600	uM
8-[5-(difluoromethyl)-3-pyridinyl]-1-(oxan-4-yl)-2H-pyrazolo[3,4-c]quinoline	1779777: Displacement of 5-TAMRA-labelled Tracer A from human GST-fused/FLAG-tagged full length ATR/human N-terminal FLAG-tagged full length ATRIP expressed in HEK293-6E cells preincubated for 15 mins followed by tracer A addition and measured after 30 mins by TR-FRET based competition binding assay	ic50	0.1970	uM
(3R)-4-[7-cyclohexylsulfonyl-2-(1H-indol-4-yl)pyrrolo[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	0.2050	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Cadmium Chloride	decreases expression, increases abundance, increases expression	4
sodium arsenite	decreases expression, increases expression	2
GSK-J4	decreases expression	1
FR900359	decreases phosphorylation	1
lasiocarpine	decreases expression, increases metabolic processing	1
bisphenol A	affects cotreatment, increases expression	1
VX-agent	increases expression	1
riddelliine	decreases expression, increases metabolic processing	1
beta-lapachone	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
perfluorooctanoic acid	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
CPG-oligonucleotide	decreases expression	1
NSC 689534	affects binding, decreases expression	1
Sunitinib	decreases expression	1
Arsenic	affects methylation	1
Benzo(a)pyrene	increases methylation	1
Cadmium	decreases expression, increases abundance	1
Caffeine	affects phosphorylation	1
Cannabidiol	decreases expression	1
Copper	affects binding, decreases expression	1
Dichlorodiphenyl Dichloroethylene	increases expression	1
Dexamethasone	affects cotreatment, increases expression	1
Doxorubicin	affects expression, affects response to substance	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Indomethacin	affects cotreatment, increases expression	1
Methyl Methanesulfonate	increases expression	1
Smoke	decreases expression	1
Tetrachlorodibenzodioxin	affects expression	1
Thiram	decreases expression	1

ChEMBL screening assays

31 unique, capped per target: 31 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4023028	Binding	Inhibition of full length recombinant human ATR /ATRIP at 1 uM relative to control	Highly Selective, Potent, and Oral mTOR Inhibitor for Treatment of Cancer as Autophagy Inducer. — *J Med Chem*

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

showing 60 of 600 trials:

NCT	Phase	Status	Title
NCT00014638	Phase 4	COMPLETED	Letrozole in Treating Postmenopausal Women With Metastatic Breast Cancer
NCT00022386	Phase 4	COMPLETED	Epoetin Alfa in Treating Chemotherapy-Related Anemia in Women With Stage I, Stage II, or Stage III Breast Cancer
NCT00029224	Phase 4	COMPLETED	Treatment With Zoledronic Acid in Patients With Breast Cancer, Multiple Myeloma, and Prostate Cancer With Cancer Related Bone Lesions
NCT00030758	Phase 4	UNKNOWN	Filgrastim or Pegfilgrastim in Preventing Neutropenia in Women Receiving Chemotherapy Following Surgery for Breast Cancer
NCT00082277	Phase 4	COMPLETED	Anastrozole Biphosphonate Study in Postmenopausal Women With Hormone-Receptor-Positive Early Breast Cancer
NCT00087620	Phase 4	TERMINATED	A Study of Capecitabine In Combination With Docetaxel vs Capecitabine Followed by Docetaxel As First-Line Treatment For Metastatic Breast Cancer
NCT00121836	Phase 4	COMPLETED	A Study of Xeloda (Capecitabine) in Women With HER2-Negative Metastatic Breast Cancer
NCT00126360	Phase 4	UNKNOWN	STARS Breast Trial (Study of Anastrozole and Radiotherapy Sequencing Pilot)
NCT00127933	Phase 4	COMPLETED	XeNA Study - A Study of Xeloda (Capecitabine) in Patients With Invasive Breast Cancer
NCT00128297	Phase 4	COMPLETED	Pamidronate Administration in Breast Cancer Patients With Bone Metastases
NCT00129597	Phase 4	UNKNOWN	Effect of Ketalar to Prevent Postoperative Chronic Pain After Mastectomy
NCT00131170	Phase 4	COMPLETED	Paravertebral Block for Breast Surgery
NCT00156039	Phase 4	COMPLETED	Randomized Trial of Follow-up Strategies in Breast Cancer
NCT00160901	Phase 4	COMPLETED	Complementary Therapies for the Reduction of Side Effects During Chemotherapy for Breast Cancer
NCT00171847	Phase 4	TERMINATED	Study of the Efficacy and Safety of Letrozole Combined With Trastuzumab in Patients With Metastatic Breast Cancer
NCT00176046	Phase 4	COMPLETED	Mistletoe Extract in Early or Advanced Breast Cancer, A Feasibility Study
NCT00190697	Phase 4	COMPLETED	A Study of LY353381 (Arzoxifene) for Patients Who Benefitted From This Drug in Other Oncology Trials and Wished to Continue Treatment
NCT00234195	Phase 4	COMPLETED	Wellbutrin XL, Major Depressive Disorder and Breast Cancer
NCT00237133	Phase 4	COMPLETED	Treatment of Locally Advanced Breast Cancer With Letrozole in Postmenopausal Women
NCT00237224	Phase 4	COMPLETED	Open Label Study of Postmenopausal Women With ER and /or PgR Positive Breast Cancer Treated With Letrozole
NCT00241046	Phase 4	TERMINATED	Letrozole in the Treatment of 1st and 2nd Line Hormone Receptor Positive Breast Cancer: Pre-therapeutic Risk Assessment
NCT00277160	Phase 4	COMPLETED	A Study of Primary Prophylaxis With Neulasta (Pegfilgrastim) Versus Secondary Prophylaxis After Chemotherapy in Elderly Subjects (>/= 65 Years Old) With Cancer
NCT00323479	Phase 4	COMPLETED	Arthralgia During Anastrozole Therapy for Breast Cancer
NCT00334139	Phase 4	COMPLETED	Effect of Zoledronic Acid on Bone Metabolism in Patients With Bone Metastasis and Prostate or Breast Cancer
NCT00356148	Phase 4	COMPLETED	The Efficacy of Prophylactic Antibiotic Administration During Breast Cancer Surgery in Overweight Patients.
NCT00372476	Phase 4	COMPLETED	Efficacy and Safety of Imatinib and Vinorelbine in Patients With Advanced Breast Cancer
NCT00413491	Phase 4	UNKNOWN	National Screening in Denmark With MR Versus Mammography and Ultrasound of Women With BRCA1 or BRCA2 Mutations
NCT00484614	Phase 4	UNKNOWN	Study the Role of Positron Emission Mammography in Pre-surgical Planning for Breast Cancer
NCT00485953	Phase 4	COMPLETED	Effect of Bisphosphonate on Bone Loss in Postmenopausal Women With Breast Cancer Initiating Aromatase Inhibitor Therapy
NCT00496678	Phase 4	COMPLETED	Trial of Patient Navigation-Activation
NCT00531973	Phase 4	UNKNOWN	A Study of Liposomal Doxorubicin in Women With Breast Cancer Exploiting Tissue Doppler Imaging
NCT00537771	Phase 4	COMPLETED	Liver Safety Under Upfront Arimidex vs Tamoxifen
NCT00544986	Phase 4	COMPLETED	A Prospective,Open-label Study of Anastrozole in Post-menopausal Women With Hormone Sensitive Advanced Breast Cancer
NCT00613275	Phase 4	COMPLETED	Patient Navigation in the Safety Net:CONNECTeDD
NCT00638599	Phase 4	COMPLETED	Comparison of Laryngeal Mask Airway (LMA®) and Tracheal Tube in Modified Radical Mastectomy on Breast Cancer
NCT00647075	Phase 4	UNKNOWN	Yunzhi as Dietary Supplement in Breast Cancer
NCT00688909	Phase 4	COMPLETED	Rheumatological Evaluation of Anastrozole and Letrozole as Adjuvant Treatment in Post-menopausal Women With Breast Cancer
NCT00699101	Phase 4	TERMINATED	Using the Conture® Multi-Lumen Balloon to Deliver Accelerated Partial Breast Brachytherapy
NCT00742222	Phase 4	COMPLETED	Electronic Xoft Intersociety Brachytherapy Trial: Electronic Brachytherapy (EBT) For Treatment of Early Stage Breast Cancer
NCT00754767	Phase 4	TERMINATED	L-Carnitine L-Tartrate in Preventing Peripheral Neuropathy Caused By Chemotherapy in Women With Metastatic Breast Cancer
NCT00756717	Phase 4	COMPLETED	Study Of MK-0752 In Combination With Tamoxifen Or Letrozole to Treat Early Stage Breast Cancer
NCT00766532	Phase 4	COMPLETED	Do Aromatase Inhibitors (AIs) Decrease Intestinal Calcium Absorption?
NCT00768222	Phase 4	COMPLETED	Coated VICRYL* Plus Suture Compared to Chinese Silk in Scheduled Breast Cancer Surgery
NCT00772824	Phase 4	COMPLETED	Study of the Effect of Glutamine Supplementation on Chemotherapy Induced Toxicities in Breast Cancer Patients
NCT00774241	Phase 4	WITHDRAWN	PRIMADOS Study:A Study of Avastin (Bevacizumab) Plus Docetaxel for First Line Treatment of Patients With Metastatic Breast Cancer
NCT00812864	Phase 4	COMPLETED	Pharmacokinetic Study of Capecitabine in Elderly Cancer Patient (≥ 75 Years)
NCT00872859	Phase 4	COMPLETED	The BREASTrial:Breast Reconstruction Evaluation Using Acellular Dermal Matrix as a Sling Trial
NCT00882089	Phase 4	COMPLETED	Use of the Contura™ Catheter in Intermediate-Risk, Pathological Stage 0, I, or II (Up to 3.0 cm) Breast Cancer Patients
NCT00882596	Phase 4	COMPLETED	Use of the Contura™ Catheter to Deliver Accelerated Partial Breast Irradiation to Low-risk Breast Cancer Patients
NCT00904410	Phase 4	COMPLETED	Early Assessment of the Response to Neo-adjuvant Chemotherapy in Breast Cancer Patients With FDG-PET
NCT00912639	Phase 4	UNKNOWN	A Clinical Trial of Paclitaxel Loaded Polymeric Micelle in Patients With Taxane-Pretreated Recurrent Breast Cancer
NCT00912938	Phase 4	UNKNOWN	Evaluate the Relationship of Bone Remodeling Markers for Skeletal Complications in Metastatic Breast Cancer Patients
NCT01035099	Phase 4	COMPLETED	RCT of Fixed vs Titrated Letrozole in Breast Cancer Patient Undergoing IVF
NCT01049295	Phase 4	UNKNOWN	Omega-3 Fatty Acids and Chemotherapy-induced Neuropathy and Inflammation in Breast Cancer
NCT01072318	Phase 4	UNKNOWN	Extended Adjuvant Treatment With Letrozole in Breast Cancer Who Complete 5 Years of Toremifene
NCT01094184	Phase 4	COMPLETED	A Study of Bevacizumab With Taxane Therapy in Participants With Triple Negative Breast Cancer
NCT01156961	Phase 4	WITHDRAWN	A Study of The Safety Profile of First-line Avastin (Bevacizumab) in Combination With Paclitaxel in Patients With Locally Recurrent or Metastatic Her2-negative Breast Cancer (AVATAX)
NCT01199432	Phase 4	COMPLETED	Comparative Efficiency of Three Regimen, CEFci, CEF and EC as Neoadjuvant Chemotherapy for Primary Breast Cancer
NCT01216254	Phase 4	UNKNOWN	Clinical Trial Comparing Outcomes of Breast Conserving Operations With Classic v High-frequency Electrocoagulation
NCT01231204	Phase 4	COMPLETED	Prevention of Post-Mastectomy Breast Pain Using Ambulatory Continuous Paravertebral Blocks

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for ATRIP across ~30M SureChEMBL compounds — explore on Sugi Predict.