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): 1,719 total — 27 pathogenic, 21 likely-pathogenic
• Phenotypes (HPO): 26
• Druggable target: yes — 3 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 64.8% of screened cell lines
• MANE Select transcript: NM_130384

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: 14 — 9 protein_coding, 4 nonsense_mediated_decay, 1 retained_intron

ENST00000320211, ENST00000346691, ENST00000412052, ENST00000634384, ENST00000635082, ENST00000635084, ENST00000635099, ENST00000635464, ENST00000639561, ENST00000885532, ENST00000949796, ENST00000949797, ENST00000949798, ENST00000949799

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
ENSE00003784929	48465487	48467645
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

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.

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

240 total, 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

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

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): HIF1A

miRNA regulators (miRDB)

4 targeting ATRIP, 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-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

DepMap (CRISPR cell-line fitness): dependent in 64.8% of screened cell lines.

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

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

UniProt features (23 total): sequence conflict 8, splice variant 3, region of interest 2, sequence variant 2, mutagenesis site 2, compositionally biased region 2, chain 1, helix 1, coiled-coil region 1, short sequence motif 1

Structure

Experimental structures (PDB)

11 structures.

PDB	Method	Resolution (Å)
4NB3	X-RAY DIFFRACTION	1.35
7XV4	X-RAY DIFFRACTION	1.6
4IGK	X-RAY DIFFRACTION	1.75
23FC	ELECTRON MICROSCOPY	2.7
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-Q8WXE1-F1	70.10	0.35

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

26 pathways

ID	Pathway
R-HSA-176187	Activation of ATR in response to replication stress
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-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-1640170	Cell Cycle
R-HSA-1643685	Disease
R-HSA-212436	Generic Transcription Pathway
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)
R-HSA-9675135	Diseases of DNA repair
R-HSA-9675136	Diseases of DNA Double-Strand Break Repair
R-HSA-9701190	Defective homologous recombination repair (HRR) due to BRCA2 loss of function

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 (3): nucleus (GO:0005634), nucleoplasm (GO:0005654), ATR-ATRIP complex (GO:0070310)

Reactome top-level categories

Rollup of top-14 pathways:

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

Rollup of top GO terms by namespace:

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
nuclear protein-containing complex	1

Protein interactions and networks

STRING

1227 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ATRIP	TOPBP1	Q92547	998
ATRIP	ATR	Q13535	998
ATRIP	ATM	Q13315	995
ATRIP	RAD9A	Q99638	986
ATRIP	RPA1	P27694	983
ATRIP	PRKDC	P78527	964
ATRIP	CLSPN	Q9HAW4	951
ATRIP	HUS1	O60921	950
ATRIP	RAD17	O75943	950
ATRIP	CHEK1	O14757	927
ATRIP	MCM7	P33993	916
ATRIP	RPA2	P15927	848
ATRIP	XRCC5	P13010	838
ATRIP	ETAA1	Q9NY74	828
ATRIP	CHEK2	O96017	821

IntAct

105 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
CINP	ATRIP	psi-mi:“MI:0915”(physical association)	0.730
CINP	ATRIP	psi-mi:“MI:0407”(direct interaction)	0.730
ATRIP	CINP	psi-mi:“MI:0407”(direct interaction)	0.730
ATRIP	CINP	psi-mi:“MI:0915”(physical association)	0.730
CINP	ATR	psi-mi:“MI:0914”(association)	0.610
ATRIP	POLR1C	psi-mi:“MI:0915”(physical association)	0.560
MOS	ATRIP	psi-mi:“MI:0915”(physical association)	0.560
ATRIP	MX2	psi-mi:“MI:0915”(physical association)	0.560
ATRIP	FAM156B	psi-mi:“MI:0915”(physical association)	0.560
LNX1	ATRIP	psi-mi:“MI:0915”(physical association)	0.560
ATRIP	METTL21A	psi-mi:“MI:0915”(physical association)	0.560
SPRY2	ATRIP	psi-mi:“MI:0915”(physical association)	0.560
SCG2	ATRIP	psi-mi:“MI:0915”(physical association)	0.560
ATRIP	TASOR2	psi-mi:“MI:0915”(physical association)	0.560
ATRIP	C1orf94	psi-mi:“MI:0915”(physical association)	0.560
MID2	ATRIP	psi-mi:“MI:0915”(physical association)	0.560
ATRIP	CDC23	psi-mi:“MI:0915”(physical association)	0.560
PCTK1	ATRIP	psi-mi:“MI:0915”(physical association)	0.560
CCDC28B	ATRIP	psi-mi:“MI:0915”(physical association)	0.560
POLR1C	ATRIP	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (212): ATRIP (Two-hybrid), ATRIP (Two-hybrid), ATRIP (Two-hybrid), ATRIP (Two-hybrid), ATRIP (Two-hybrid), ATRIP (Two-hybrid), ATRIP (Two-hybrid), ATRIP (Two-hybrid), ATRIP (Two-hybrid), ATRIP (Two-hybrid), ATRIP (Two-hybrid), ATRIP (Two-hybrid), LNX1 (Two-hybrid), C1orf94 (Two-hybrid), METTL21A (Two-hybrid)

ESM2 similar proteins: A0A1L8ENT6, A2BGP7, A2CJ06, B1H1W9, F6RRD7, O00124, O55036, P54274, Q1LV50, Q1LWH4, Q1T7B8, Q28HU3, Q3KNJ2, Q3U1D0, Q3US16, Q4KLN8, Q4V832, Q5I0E6, Q5I2W8, Q5NVA9, Q5RA37, Q5RET9, Q5XI46, Q5ZIN2, Q6AYI4, Q6DRL4, Q6IQ49, Q6IRN0, Q6NV18, Q6P1H6, Q7Z2Z1, Q7Z4M0, Q8BJW7, Q8BKT3, Q8BMG1, Q8BMI4, Q8BQ33, Q8IXW5, Q8K1J5, Q8VC34

Diamond homologs: Q8BMG1, Q8WXE1, Q9N077

SIGNOR signaling

7 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

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 82 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
Processing of DNA double-strand break ends	6	12.0×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

1719 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	27
Likely pathogenic	21
Uncertain significance	1087
Likely benign	485
Benign	25

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1069131	NM_033629.6(TREX1):c.403C>T (p.Gln135Ter)	Pathogenic
126386	NM_033629.6(TREX1):c.366_368dup (p.Ala123_His124insAla)	Pathogenic
1430592	NM_033629.6(TREX1):c.153_166del (p.Gln51fs)	Pathogenic
1433355	NM_033629.6(TREX1):c.296_299dup (p.Phe100fs)	Pathogenic
1455316	NM_033629.6(TREX1):c.5del (p.Gly2fs)	Pathogenic
2127740	NM_033629.6(TREX1):c.18dup (p.Pro7fs)	Pathogenic
2930302	NM_033629.6(TREX1):c.226_233dup (p.Ser78fs)	Pathogenic
2936844	NM_033629.6(TREX1):c.349C>T (p.Gln117Ter)	Pathogenic
2936991	NM_033629.6(TREX1):c.522_523delinsTT (p.Arg174_Lys175delinsSerTer)	Pathogenic
2942588	NM_033629.6(TREX1):c.205_206del (p.Leu69fs)	Pathogenic
2942595	NM_033629.6(TREX1):c.371_381del (p.His124fs)	Pathogenic
2944466	NM_033629.6(TREX1):c.76_80dup (p.Gln28fs)	Pathogenic
2945896	NM_033629.6(TREX1):c.69dup (p.Pro25fs)	Pathogenic
2947312	NM_033629.6(TREX1):c.565C>T (p.Gln189Ter)	Pathogenic
2948275	NM_033629.6(TREX1):c.366_367del (p.Ala123fs)	Pathogenic
2952190	NM_033629.6(TREX1):c.141_151del (p.Pro48fs)	Pathogenic
369666	NM_033629.6(TREX1):c.629G>A (p.Trp210Ter)	Pathogenic
4182	NM_033629.6(TREX1):c.602T>A (p.Val201Asp)	Pathogenic
4184	NM_033629.6(TREX1):c.598G>A (p.Asp200Asn)	Pathogenic
4185	NM_033629.6(TREX1):c.52G>A (p.Asp18Asn)	Pathogenic
4187	NM_033629.6(TREX1):c.703_706dup (p.Thr236fs)	Pathogenic
449514	NM_033629.6(TREX1):c.703dup (p.Val235fs)	Pathogenic
4785848	NM_033629.6(TREX1):c.260_261del (p.Leu87fs)	Pathogenic
4845418	NM_033629.6(TREX1):c.853_875del (p.Glu285fs)	Pathogenic
617444	NM_033629.6(TREX1):c.581del (p.Ser194fs)	Pathogenic
843202	NM_033629.6(TREX1):c.416del (p.Ala139fs)	Pathogenic
850507	NM_033629.6(TREX1):c.236_243del (p.Pro79fs)	Pathogenic
126388	NM_033629.6(TREX1):c.397del (p.Leu133fs)	Likely pathogenic
1339479	NM_033629.6(TREX1):c.79_96del (p.Ser27_Thr32del)	Likely pathogenic
1344583	NM_033629.6(TREX1):c.830_833dup (p.Asp278fs)	Likely pathogenic

SpliceAI

2524 predictions. Top by Δscore:

Variant	Effect	Δscore
3:48447088:GTCCA:G	donor_gain	1.0000
3:48447093:G:GG	donor_gain	1.0000
3:48451724:TACAG:T	acceptor_loss	1.0000
3:48451725:ACAGA:A	acceptor_loss	1.0000
3:48451726:CAGAT:C	acceptor_loss	1.0000
3:48451727:A:AG	acceptor_gain	1.0000
3:48451727:A:C	acceptor_loss	1.0000
3:48451728:G:GG	acceptor_gain	1.0000
3:48451880:A:T	donor_gain	1.0000
3:48451885:G:GT	donor_gain	1.0000
3:48451895:AAAAG:A	donor_loss	1.0000
3:48451896:AAAG:A	donor_loss	1.0000
3:48451897:AAG:A	donor_loss	1.0000
3:48451898:AGGT:A	donor_loss	1.0000
3:48451899:GGTG:G	donor_loss	1.0000
3:48451900:G:A	donor_loss	1.0000
3:48451901:T:A	donor_loss	1.0000
3:48454295:TCCA:T	acceptor_loss	1.0000
3:48454297:CA:C	acceptor_loss	1.0000
3:48454298:A:AG	acceptor_gain	1.0000
3:48454298:A:C	acceptor_loss	1.0000
3:48454299:G:GA	acceptor_gain	1.0000
3:48454299:GCT:G	acceptor_gain	1.0000
3:48454299:GCTCC:G	acceptor_gain	1.0000
3:48454415:TCAGG:T	donor_loss	1.0000
3:48454416:CAGGT:C	donor_loss	1.0000
3:48454417:AGGT:A	donor_loss	1.0000
3:48454418:GGTAA:G	donor_loss	1.0000
3:48454419:G:GA	donor_loss	1.0000
3:48454420:T:A	donor_loss	1.0000

AlphaMissense

5124 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:48454322:T:C	L192P	0.997
3:48454327:T:C	F194L	0.997
3:48454329:T:A	F194L	0.997
3:48454329:T:G	F194L	0.997
3:48451784:G:C	R146P	0.996
3:48454336:G:C	A197P	0.995
3:48451781:T:C	L145S	0.993
3:48454328:T:C	F194S	0.993
3:48454301:T:C	L185P	0.992
3:48451789:T:C	S148P	0.991
3:48454332:A:C	K195N	0.991
3:48454332:A:T	K195N	0.991
3:48460519:A:C	S489R	0.991
3:48460521:C:A	S489R	0.991
3:48460521:C:G	S489R	0.991
3:48454315:T:C	S190P	0.988
3:48464867:T:A	W698R	0.988
3:48464867:T:C	W698R	0.988
3:48464937:G:C	R721P	0.988
3:48457344:T:C	F253L	0.985
3:48457346:T:A	F253L	0.985
3:48457346:T:G	F253L	0.985
3:48460208:G:A	G385E	0.985
3:48460508:T:C	L485P	0.985
3:48454310:T:C	L188S	0.984
3:48460499:T:C	L482P	0.984
3:48451761:G:C	K138N	0.983
3:48451761:G:T	K138N	0.983
3:48454331:A:T	K195I	0.983
3:48465039:T:A	V755D	0.983

dbSNP variants (sampled 300 via entrez): RS1000009304 (3:48453600 A>G), RS1000061589 (3:48453411 G>A,C), RS1000190732 (3:48447040 C>A,T), RS1000372836 (3:48461095 A>G), RS1000680376 (3:48449719 A>G), RS1001416785 (3:48467882 C>T), RS1001645734 (3:48462610 G>A), RS1001684596 (3:48455405 A>G), RS1001736841 (3:48455080 C>G,T), RS1001904036 (3:48464175 T>C), RS1002076286 (3:48449245 C>G,T), RS1002100514 (3:48449510 T>A), RS1002107451 (3:48449023 T>C), RS1002163260 (3:48448038 T>C), RS1002379489 (3:48464519 G>A,C)

Disease associations

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

GenCC curated gene-disease

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

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
hereditary breast carcinoma	Limited	AD

Mondo (13): 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), thrombotic microangiopathy (MONDO:0019737), breast ductal adenocarcinoma (MONDO:0005590), inherited retinal dystrophy (MONDO:0019118), intellectual disability (MONDO:0001071), chilblain lupus (MONDO:0019557), vascular dementia (MONDO:0004648), cerebral arteriopathy with subcortical infarcts and leukoencephalopathy (MONDO:0007432), Seckel syndrome (MONDO:0019342), breast cancer (MONDO:0007254)

Orphanet (10): 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), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

26 total (28 of 26 shown, 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
HP:0002725	Systemic lupus erythematosus
HP:0000556	Retinal dystrophy

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST004131_23	Inflammatory bowel disease	1.000000e-33
GCST004132_17	Crohn’s disease	3.000000e-23
GCST004133_11	Ulcerative colitis	8.000000e-20
GCST010698_80	Subcortical volume (min-P)	3.000000e-24
GCST010699_110	Brain morphology (min-P)	4.000000e-08
GCST010701_52	Cortical surface area (MOSTest)	1.000000e-16
GCST010702_36	Subcortical volume (MOSTest)	1.000000e-10
GCST010703_262	Brain morphology (MOSTest)	2.000000e-13

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004346	neuroimaging measurement

MeSH disease descriptors (7)

Descriptor	Name	Tree numbers
D018270	Carcinoma, Ductal, Breast	C04.557.470.200.025.232.500; C04.557.470.615.132.500; C04.588.180.390; C17.800.090.500.390
D015140	Dementia, Vascular	C10.228.140.300.400; C10.228.140.300.510.800.500; C10.228.140.380.230; C10.228.140.695.500; C14.907.137.126.372.500; C14.907.253.560.350.500; F03.615.400.350
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
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
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

3 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 2,287 (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
CHEMBL4647810	ELIMUSERTIB	1	297
CHEMBL4650286	M4344	1	521

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

Binding affinities (BindingDB)

523 measured of 523 human assays (524 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
(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
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
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
3-{1-Methyl-5-[(3R)-3-methylmorpholin-4-yl]-3-(1H-pyrazol-3-yl)-1H-pyrazolo[4,3-b]pyridin-7-yl}benzonitrile	IC50	2 nM	US-12371430: 5-morpholin-4-yl-pyrazolo[4,3-b]pyridine derivatives
7-(6-Methanesulfinyl-2-methyl-pyridin-3-yl)-1-methyl-5-((R)-3-methyl-morpholin-4-yl)-3-(1H-pyrazol-3-yl)-1H-pyrazolo[4,3-b]pyridine	IC50	2.1 nM	US-12371430: 5-morpholin-4-yl-pyrazolo[4,3-b]pyridine derivatives
(3R)-4-[7-(3,6-Dihydro-2H-pyran-4-yl)-1-methyl-3-(1H-pyrazol-3-yl)-1H-pyrazolo[4,3-b]pyridin-5-yl]-3-methylmorpholine	IC50	2.2 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-furan-3-yl)-1H-pyrazolo[4,3-b]pyridine	IC50	2.2 nM	US-12371430: 5-morpholin-4-yl-pyrazolo[4,3-b]pyridine derivatives

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)

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

Trial	Phase	Status	Title
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
NCT00688909	PHASE4	COMPLETED	Rheumatological Evaluation of Anastrozole and Letrozole as Adjuvant Treatment in Post-menopausal Women With Breast Cancer
NCT00699101	PHASE4	TERMINATED	Using the Conture® Multi-Lumen Balloon to Deliver Accelerated Partial Breast Brachytherapy
NCT00742222	PHASE4	COMPLETED	Electronic Xoft Intersociety Brachytherapy Trial: Electronic Brachytherapy (EBT) For Treatment of Early Stage Breast Cancer
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