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Target not currently curated in GtoImmuPdb
Target id: 1988
Nomenclature: checkpoint kinase 2
Abbreviated Name: Chk2
Family: RAD53 family, CHK1 subfamily
Gene and Protein Information | ||||||
Species | TM | AA | Chromosomal Location | Gene Symbol | Gene Name | Reference |
Human | - | 543 | 22q12.1 | CHEK2 | checkpoint kinase 2 | |
Mouse | - | 546 | 5 F | Chek2 | checkpoint kinase 2 | |
Rat | - | 545 | 12 q16 | Chek2 | checkpoint kinase 2 |
Previous and Unofficial Names |
CDS1 | HuCds1 | PP1425 | RAD53 |
Database Links | |
Alphafold | O96017 (Hs), Q9Z265 (Mm) |
BRENDA | 2.7.11.1 |
ChEMBL Target | CHEMBL2527 (Hs) |
Ensembl Gene | ENSG00000183765 (Hs), ENSMUSG00000029521 (Mm), ENSRNOG00000037509 (Rn) |
Entrez Gene | 11200 (Hs), 50883 (Mm), 114212 (Rn) |
Human Protein Atlas | ENSG00000183765 (Hs) |
KEGG Enzyme | 2.7.11.1 |
KEGG Gene | hsa:11200 (Hs), mmu:50883 (Mm), rno:114212 (Rn) |
OMIM | 604373 (Hs) |
Orphanet | ORPHA119394 (Hs) |
Pharos | O96017 (Hs) |
RefSeq Nucleotide | NM_001005735 (Hs), NM_016681 (Mm), NM_053677 (Rn) |
RefSeq Protein | NP_001005735 (Hs), NP_057890 (Mm), NP_446129 (Rn) |
UniProtKB | O96017 (Hs), Q9Z265 (Mm) |
Wikipedia | CHEK2 (Hs) |
Selected 3D Structures | |||||||||||||
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Enzyme Reaction | ||||
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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 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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DiscoveRx KINOMEscan® screen | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
A screen of 72 inhibitors against 456 human kinases. Quantitative data were derived using DiscoveRx KINOMEscan® platform. http://www.discoverx.com/services/drug-discovery-development-services/kinase-profiling/kinomescan Reference: 5,14 |
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Key to terms and symbols | Click column headers to sort | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Target used in screen: CHEK2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Displaying the top 10 most potent ligands View all ligands in screen » |
EMD Millipore KinaseProfilerTM screen/Reaction Biology Kinase HotspotSM screen | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
A screen profiling 158 kinase inhibitors (Calbiochem Protein Kinase Inhibitor Library I and II, catalogue numbers 539744 and 539745) for their inhibitory activity at 1µM and 10µM against 234 human recombinant kinases using the EMD Millipore KinaseProfilerTM service. A screen profiling the inhibitory activity of 178 commercially available kinase inhibitors at 0.5µM against a panel of 300 recombinant protein kinases using the Reaction Biology Corporation Kinase HotspotSM platform. http://www.millipore.com/techpublications/tech1/pf3036 http://www.reactionbiology.com/webapps/main/pages/kinase.aspx Reference: 1,7 |
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Target used in screen: CHK2/CHK2 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Displaying the top 10 most potent ligands View all ligands in screen » |
Clinically-Relevant Mutations and Pathophysiology | ||||||||||||||
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1. Anastassiadis T, Deacon SW, Devarajan K, Ma H, Peterson JR. (2011) Comprehensive assay of kinase catalytic activity reveals features of kinase inhibitor selectivity. Nat Biotechnol, 29 (11): 1039-45. [PMID:22037377]
2. Anderson VE, Walton MI, Eve PD, Boxall KJ, Antoni L, Caldwell JJ, Aherne W, Pearl LH, Oliver AW, Collins I et al.. (2011) CCT241533 is a potent and selective inhibitor of CHK2 that potentiates the cytotoxicity of PARP inhibitors. Cancer Res, 71 (2): 463-72. [PMID:21239475]
3. Blasina A, Hallin J, Chen E, Arango ME, Kraynov E, Register J, Grant S, Ninkovic S, Chen P, Nichols T et al.. (2008) Breaching the DNA damage checkpoint via PF-00477736, a novel small-molecule inhibitor of checkpoint kinase 1. Mol Cancer Ther, 7 (8): 2394-404. [PMID:18723486]
4. Busby EC, Leistritz DF, Abraham RT, Karnitz LM, Sarkaria JN. (2000) The radiosensitizing agent 7-hydroxystaurosporine (UCN-01) inhibits the DNA damage checkpoint kinase hChk1. Cancer Res, 60 (8): 2108-12. [PMID:10786669]
5. Davis MI, Hunt JP, Herrgard S, Ciceri P, Wodicka LM, Pallares G, Hocker M, Treiber DK, Zarrinkar PP. (2011) Comprehensive analysis of kinase inhibitor selectivity. Nat Biotechnol, 29 (11): 1046-51. [PMID:22037378]
6. Fedorov O, Marsden B, Pogacic V, Rellos P, Müller S, Bullock AN, Schwaller J, Sundström M, Knapp S. (2007) A systematic interaction map of validated kinase inhibitors with Ser/Thr kinases. Proc Natl Acad Sci USA, 104 (51): 20523-8. [PMID:18077363]
7. Gao Y, Davies SP, Augustin M, Woodward A, Patel UA, Kovelman R, Harvey KJ. (2013) A broad activity screen in support of a chemogenomic map for kinase signalling research and drug discovery. Biochem J, 451 (2): 313-28. [PMID:23398362]
8. Gingrich DE, Lisko JG, Curry MA, Cheng M, Quail M, Lu L, Wan W, Albom MS, Angeles TS, Aimone LD et al.. (2012) Discovery of an orally efficacious inhibitor of anaplastic lymphoma kinase. J Med Chem, 55 (10): 4580-93. [PMID:22564207]
9. Jorda R, Havlíček L, Šturc A, Tušková D, Daumová L, Alam M, Škerlová J, Nekardová M, Peřina M, Pospíšil T et al.. (2019) 3,5,7-Substituted Pyrazolo[4,3- d]pyrimidine Inhibitors of Cyclin-Dependent Kinases and Their Evaluation in Lymphoma Models. J Med Chem, 62 (9): 4606-4623. DOI: 10.1021/acs.jmedchem.9b00189 [PMID:30943029]
10. King C, Diaz HB, McNeely S, Barnard D, Dempsey J, Blosser W, Beckmann R, Barda D, Marshall MS. (2015) LY2606368 Causes Replication Catastrophe and Antitumor Effects through CHK1-Dependent Mechanisms. Mol Cancer Ther, 14 (9): 2004-13. [PMID:26141948]
11. Oliver AW, Paul A, Boxall KJ, Barrie SE, Aherne GW, Garrett MD, Mittnacht S, Pearl LH. (2006) Trans-activation of the DNA-damage signalling protein kinase Chk2 by T-loop exchange. EMBO J, 25 (13): 3179-90. [PMID:16794575]
12. Osborne JD, Matthews TP, McHardy T, Proisy N, Cheung KM, Lainchbury M, Brown N, Walton MI, Eve PD, Boxall KJ et al.. (2016) Multiparameter Lead Optimization to Give an Oral Checkpoint Kinase 1 (CHK1) Inhibitor Clinical Candidate: (R)-5-((4-((Morpholin-2-ylmethyl)amino)-5-(trifluoromethyl)pyridin-2-yl)amino)pyrazine-2-carbonitrile (CCT245737). J Med Chem, 59 (11): 5221-37. [PMID:27167172]
13. Oza V, Ashwell S, Almeida L, Brassil P, Breed J, Deng C, Gero T, Grondine M, Horn C, Ioannidis S et al.. (2012) Discovery of checkpoint kinase inhibitor (S)-5-(3-fluorophenyl)-N-(piperidin-3-yl)-3-ureidothiophene-2-carboxamide (AZD7762) by structure-based design and optimization of thiophenecarboxamide ureas. J Med Chem, 55 (11): 5130-42. [PMID:22551018]
14. Wodicka LM, Ciceri P, Davis MI, Hunt JP, Floyd M, Salerno S, Hua XH, Ford JM, Armstrong RC, Zarrinkar PP et al.. (2010) Activation state-dependent binding of small molecule kinase inhibitors: structural insights from biochemistry. Chem Biol, 17 (11): 1241-9. [PMID:21095574]
CHK1 subfamily: checkpoint kinase 2. Last modified on 05/04/2019. Accessed on 06/11/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1988.