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ATR serine/threonine kinase

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Target id: 1935

Nomenclature: ATR serine/threonine kinase

Abbreviated Name: ATR

Family: ATR subfamily

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 2644 3q23 ATR ATR serine/threonine kinase
Mouse - 2635 9 E3.3 Atr ataxia telangiectasia and Rad3 related
Rat - 2636 8q31 Atr ATR serine/threonine kinase
Previous and Unofficial Names Click here for help
FRP1 | MEC1 | mitosis entry checkpoint 1, homolog (S. cerevisiae) | SCKL | SCKL1
Database Links Click here for help
Alphafold Q13535 (Hs), Q9JKK8 (Mm)
BRENDA 2.7.11.1
CATH/Gene3D 1.10.1070.11, 1.25.10.10, 1.25.40.10
ChEMBL Target CHEMBL5024 (Hs)
Ensembl Gene ENSG00000175054 (Hs), ENSMUSG00000032409 (Mm), ENSRNOG00000010027 (Rn)
Entrez Gene 545 (Hs), 245000 (Mm), 685055 (Rn)
Human Protein Atlas ENSG00000175054 (Hs)
KEGG Enzyme 2.7.11.1
KEGG Gene hsa:545 (Hs), mmu:245000 (Mm), rno:685055 (Rn)
OMIM 601215 (Hs)
Orphanet ORPHA118896 (Hs)
Pharos Q13535 (Hs)
RefSeq Nucleotide NM_001184 (Hs), NM_019864 (Mm), XM_003750561 (Rn)
RefSeq Protein NP_001175 (Hs), NP_063917 (Mm), XP_003750609 (Rn)
UniProtKB Q13535 (Hs), Q9JKK8 (Mm)
Wikipedia ATR (Hs)
Enzyme Reaction Click here for help
EC Number: 2.7.11.1

Download all structure-activity data for this target as a CSV file go icon to follow link

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
camonsertib Small molecule or natural product Hs Inhibition 10.7 pKi 7
⤷ pKi 10.7 (Ki 2.2x10-11 M) [7]
Description: Determined in a biochemical assay measuring inhibition of ATR-mediated substrate (p53) phosphorylation.
gartisertib Small molecule or natural product Hs Inhibition >9.8 pKi 10
⤷ pKi >9.8 (Ki <1.5x10-10 M) [10]
berzosertib Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition >9.7 pKi 3
⤷ pKi >9.7 (Ki <2x10-10 M) [3]
VE-821 Small molecule or natural product Primary target of this compound Hs Inhibition 7.9 pKi 6
⤷ pKi 7.9 (Ki 1.3x10-8 M) [6]
tuvusertib Small molecule or natural product Hs Inhibition 6.0 – 8.0 pKi 1
⤷ pKi 6.0 – 8.0 (Ki 1x10-6 – 1x10-8 M) [1]
Description: This is 'binned' range for inhibition constant that's provided in the reference patent
ceralasertib Small molecule or natural product Primary target of this compound Hs Inhibition 9.0 pIC50 9
⤷ pIC50 9.0 (IC50 1x10-9 M) [9]
Description: Inhibition of isolated enzyme
AZ20 Small molecule or natural product Primary target of this compound Ligand has a PDB structure Hs Inhibition 8.3 pIC50 4
⤷ pIC50 8.3 (IC50 5x10-9 M) [4]
Description: Inhibition of ATR immunoprecipitated from HeLa cells.
elimusertib Small molecule or natural product Hs Inhibition 8.1 pIC50 5
⤷ pIC50 8.1 (IC50 7x10-9 M) [5]
Description: In vitro biochemical inhibition of ATR kinase activity.
dactolisib Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.7 pIC50 8
⤷ pIC50 7.7 (IC50 2.1x10-8 M) [8]
BAY-8400 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 6.4 pIC50 2
⤷ pIC50 6.4 (IC50 3.94x10-7 M) [2]
Clinically-Relevant Mutations and Pathophysiology Click here for help
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. Ahmad N, Boyall D, Charrier JD, Davis C, Davis R, Durrant S, Etxebarria I Jardi G, Fraysse D, Jiminez JM, Kay D et al.. (2014) Compounds useful as inhibitors of atr kinase. Patent number: WO2014089379A1. Assignee: Vertex Pharmaceuticals Inc.. Priority date: 07/12/2012. Publication date: 12/06/2014.

2. Berger M, Wortmann L, Buchgraber P, Lücking U, Zitzmann-Kolbe S, Wengner AM, Bader B, Bömer U, Briem H, Eis K et al.. (2021) BAY-8400: A Novel Potent and Selective DNA-PK Inhibitor which Shows Synergistic Efficacy in Combination with Targeted Alpha Therapies. J Med Chem, 64 (17): 12723-12737. [PMID:34428039]

3. 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]

4. 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]

5. 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

6. 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]

7. Roulston A, Zimmermann M, Papp R, Skeldon A, Pellerin C, Dumas-Bérube É, Dumais V, Dorich S, Fader LD, Fournier S et al.. (2022) RP-3500: A Novel, Potent, and Selective ATR Inhibitor that is Effective in Preclinical Models as a Monotherapy and in Combination with PARP Inhibitors. Mol Cancer Ther, 21 (2): 245-256. [PMID:34911817]

8. 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]

9. 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]

10. Zenke FT, Zimmermann A, Dahmen H, Elenbaas B, Pollard J, Reaper P, Bagrodia S, Spilker ME, Amendt C, Blaukat A. Abstract 369: Antitumor activity of M4344, a potent and selective ATR inhibitor, in monotherapy and combination therapy. Accessed on 28/07/2021. Modified on 28/07/2021. cancerres.aacrjournals.org, https://cancerres.aacrjournals.org/content/79/13_Supplement/369. DOI: 10.1158/1538-7445.AM2019-369

How to cite this page

ATR subfamily: ATR serine/threonine kinase. Last modified on 01/08/2022. Accessed on 19/04/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetomalariapharmacology.org/GRAC/ObjectDisplayForward?objectId=1935.