ATR serine/threonine kinase | ATR subfamily | IUPHAR/BPS Guide to PHARMACOLOGY

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ATR serine/threonine kinase

Target not currently curated in GtoImmuPdb

Target id: 1935

Nomenclature: ATR serine/threonine kinase

Abbreviated Name: ATR

Family: ATR subfamily

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 2644 3q23 ATR ATR serine/threonine kinase
Mouse - 2641 9 E4 Atr ataxia telangiectasia and Rad3 related
Rat - 2636 8q31 Atr ATR serine/threonine kinase
Previous and Unofficial Names
FRP1 | MEC1 | mitosis entry checkpoint 1, homolog (S. cerevisiae) | SCKL | SCKL1
Database Links
BRENDA
CATH/Gene3D
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
KEGG Gene
OMIM
Orphanet
Pharos
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Enzyme Reaction
EC Number: 2.7.11.1

Download all structure-activity data for this target as a CSV file

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
berzosertib Hs Inhibition >9.7 pKi 1
pKi >9.7 (Ki <2x10-10 M) [1]
VE-821 Hs Inhibition 7.9 pKi 4
pKi 7.9 (Ki 1.3x10-8 M) [4]
ceralasertib Hs Inhibition 9.0 pIC50 6
pIC50 9.0 (IC50 1x10-9 M) [6]
Description: Inhibition of isolated enzyme
AZ20 Hs Inhibition 8.3 pIC50 2
pIC50 8.3 (IC50 5x10-9 M) [2]
Description: Inhibition of ATR immunoprecipitated from HeLa cells.
BAY1895344 Hs Inhibition 8.1 pIC50 3
pIC50 8.1 (IC50 7x10-9 M) [3]
Description: In vitro biochemical inhibition of ATR kinase activity.
dactolisib Hs Inhibition 7.7 pIC50 5
pIC50 7.7 (IC50 2.1x10-8 M) [5]
Clinically-Relevant Mutations and Pathophysiology
Disease:  Cutaneous telangiectasia and cancer syndrome, familial
Synonyms: Familial cutaneous telangiectasia and oropharyngeal predisposition cancer syndrome [Orphanet: ORPHA313846]
OMIM: 614564
Orphanet: ORPHA313846
Disease:  Seckel syndrome 1
Synonyms: Seckel syndrome [Orphanet: ORPHA808] [Disease Ontology: DOID:0050569]
Disease Ontology: DOID:0050569
OMIM: 210600
Orphanet: ORPHA808

References

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1. Fokas E, Prevo R, Pollard JR, Reaper PM, Charlton PA, Cornelissen B, Vallis KA, Hammond EM, Olcina MM, Gillies McKenna W et al.. (2012) Targeting ATR in vivo using the novel inhibitor VE-822 results in selective sensitization of pancreatic tumors to radiation. Cell Death Dis, 3: e441. [PMID:23222511]

2. Foote KM, Blades K, Cronin A, Fillery S, Guichard SS, Hassall L, Hickson I, Jacq X, Jewsbury PJ, McGuire TM et al.. (2013) Discovery of 4-{4-[(3R)-3-Methylmorpholin-4-yl]-6-[1-(methylsulfonyl)cyclopropyl]pyrimidin-2-yl}-1H-indole (AZ20): a potent and selective inhibitor of ATR protein kinase with monotherapy in vivo antitumor activity. J. Med. Chem., 56 (5): 2125-38. [PMID:23394205]

3. Luecking UT, Lefranc J, Wengner A, Wortmann L, Schck H, Briem H, Siesmeister G, Lienau P, Schatz C, Bader B et al.. (2017) Abstract 983: Identification of potent, highly selective and orally available ATR inhibitor BAY 1895344 with favorable PK properties and promising efficacy in monotherapy and combination in preclinical tumor models. Cancer Research, 77 (13 (Supplement)). DOI: 10.1158/1538-7445.AM2017-983

4. Reaper PM, Griffiths MR, Long JM, Charrier JD, Maccormick S, Charlton PA, Golec JM, Pollard JR. (2011) Selective killing of ATM- or p53-deficient cancer cells through inhibition of ATR. Nat. Chem. Biol., 7 (7): 428-30. [PMID:21490603]

5. Toledo LI, Murga M, Zur R, Soria R, Rodriguez A, Martinez S, Oyarzabal J, Pastor J, Bischoff JR, Fernandez-Capetillo O. (2011) A cell-based screen identifies ATR inhibitors with synthetic lethal properties for cancer-associated mutations. Nat. Struct. Mol. Biol., 18 (6): 721-7. [PMID:21552262]

6. Vendetti FP, Lau A, Schamus S, Conrads TP, O'Connor MJ, Bakkenist CJ. (2015) The orally active and bioavailable ATR kinase inhibitor AZD6738 potentiates the anti-tumor effects of cisplatin to resolve ATM-deficient non-small cell lung cancer in vivo. Oncotarget, 6 (42): 44289-305. [PMID:26517239]

How to cite this page

ATR subfamily: ATR serine/threonine kinase. Last modified on 06/08/2019. Accessed on 29/09/2020. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1935.