checkpoint kinase 1 | CHK1 subfamily | IUPHAR/BPS Guide to PHARMACOLOGY

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checkpoint kinase 1

Target not currently curated in GtoImmuPdb

Target id: 1987

Nomenclature: checkpoint kinase 1

Abbreviated Name: Chk1

Family: CHK1 subfamily

Annotation status:  image of an orange circle Annotated and awaiting review. Please contact us if you can help with reviewing.  » Email us

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 476 11q24.2 CHEK1 checkpoint kinase 1
Mouse - 476 9 A5.3 Chek1 checkpoint kinase 1
Rat - 476 8 q21 Chek1 checkpoint kinase 1
Database Links
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
RefSeq Nucleotide
RefSeq Protein
Selected 3D Structures
Image of receptor 3D structure from RCSB PDB
Description:  The 1.7 A Crystal structure of human cell cycle checkpoint kinase CHK1
PDB Id:  1IA8
Resolution:  1.7Å
Species:  Human
References:  6
Image of receptor 3D structure from RCSB PDB
Description:  X-Ray Crystal structure of compound 40 bound to human chk1 kinase domain
Resolution:  1.4Å
Species:  Human
References:  11
Enzyme Reaction
EC Number:

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

Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
CHIR-124 Hs Inhibition 9.5 pIC50 19
pIC50 9.5 (IC50 3.2x10-10 M) [19]
PF-477736 Hs Inhibition 9.3 pIC50 4
pIC50 9.3 (IC50 4.9x10-10 M) [4]
prexasertib Hs Inhibition 9.1 pIC50 15
pIC50 9.1 (IC50 9x10-10 M) [15]
Description: Biochemical assay using purified enzyme.
CCT245737 Hs Inhibition 8.9 pIC50 20
pIC50 8.9 (IC50 1.3x10-9 M) [20]
MK-8776 Hs Inhibition 8.5 pIC50 16
pIC50 8.5 (IC50 3x10-9 M) [16]
compound 25 [PMID: 17935989] Hs Inhibition 8.4 pIC50 23
pIC50 8.4 (IC50 4x10-9 M) [23]
AZD7762 Hs Inhibition 8.3 pIC50 21
pIC50 8.3 (IC50 5x10-9 M) [21]
rabusertib Hs Inhibition 8.1 pIC50 14
pIC50 8.1 (IC50 7x10-9 M) [14]
CCT244747 Hs Inhibition 8.1 pIC50 17
pIC50 8.1 (IC50 7.7x10-9 M) [17]
SB 218078 Hs Inhibition 7.8 pIC50 12
pIC50 7.8 (IC50 1.5x10-8 M) [12]
7-hydroxystaurosporine Hs Inhibition 7.5 – 8.1 pIC50 5,13,22
pIC50 7.5 – 8.1 (IC50 3.5x10-8 – 7x10-9 M) [5,13,22]
compound 33 [PMID: 19364658] Hs Inhibition 7.1 pIC50 18
pIC50 7.1 (IC50 9x10-8 M) [18]
isogranulatimide Hs Inhibition 7.0 pIC50 7,13
pIC50 7.0 (IC50 1x10-7 M) [7,13]
compound 25 [PMID: 20855207] Hs Inhibition 6.8 pIC50 3
pIC50 6.8 (IC50 1.4x10-7 M) [3]
CCT241533 Hs Inhibition 6.7 pIC50 2
pIC50 6.7 (IC50 1.9x10-7 M) [2]
BX-795 Hs Inhibition 6.3 pIC50 9
pIC50 6.3 (IC50 5.1x10-7 M) [9]
BX-912 Hs Inhibition 6.1 pIC50 9
pIC50 6.1 (IC50 8.3x10-7 M) [9]
DiscoveRx KINOMEscan® screen
A screen of 72 inhibitors against 456 human kinases. Quantitative data were derived using DiscoveRx KINOMEscan® platform.
Reference: 8,24

Key to terms and symbols Click column headers to sort
Target used in screen: CHEK1
Ligand Sp. Type Action Value Parameter
lestaurtinib Hs Inhibitor Inhibition 8.6 pKd
staurosporine Hs Inhibitor Inhibition 8.5 pKd
JNJ-28312141 Hs Inhibitor Inhibition 8.0 pKd
NVP-TAE684 Hs Inhibitor Inhibition 7.4 pKd
sunitinib Hs Inhibitor Inhibition 6.5 pKd
ruboxistaurin Hs Inhibitor Inhibition 6.3 pKd
KW-2449 Hs Inhibitor Inhibition 6.2 pKd
SU-14813 Hs Inhibitor Inhibition 5.9 pKd
dovitinib Hs Inhibitor Inhibition 5.9 pKd
midostaurin Hs Inhibitor Inhibition 5.9 pKd
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.

Reference: 1,10

Key to terms and symbols Click column headers to sort
Target used in screen: CHK1/CHK1
Ligand Sp. Type Action % Activity remaining at 0.5µM % Activity remaining at 1µM % Activity remaining at 10µM
staurosporine Hs Inhibitor Inhibition 1.6 -1.0 -0.5
K-252a Hs Inhibitor Inhibition 2.6 1.0 -1.0
SB 218078 Hs Inhibitor Inhibition 3.6 25.0 20.0
JAK3 inhibitor VI Hs Inhibitor Inhibition 6.0 10.0 3.0
Gö 6976 Hs Inhibitor Inhibition 8.0 2.0 0.0
SU11652 Hs Inhibitor Inhibition 15.1 24.0 3.0
Syk inhibitor Hs Inhibitor Inhibition 19.5 16.0 7.0
JAK inhibitor I Hs Inhibitor Inhibition 22.9 37.0 24.0
isogranulatimide Hs Inhibitor Inhibition 24.6 18.0 14.0
PKR inhibitor Hs Inhibitor Inhibition 27.1 35.0 8.0
Displaying the top 10 most potent ligands  View all ligands in screen »


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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. Belanger DB, Williams MJ, Curran PJ, Mandal AK, Meng Z, Rainka MP, Yu T, Shih NY, Siddiqui MA, Liu M et al.. (2010) Discovery of orally bioavailable imidazo[1,2-a]pyrazine-based Aurora kinase inhibitors. Bioorg. Med. Chem. Lett., 20 (22): 6739-43. [PMID:20855207]

4. 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]

5. 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]

6. Chen P, Luo C, Deng Y, Ryan K, Register J, Margosiak S, Tempczyk-Russell A, Nguyen B, Myers P, Lundgren K et al.. (2000) The 1.7 A crystal structure of human cell cycle checkpoint kinase Chk1: implications for Chk1 regulation. Cell, 100 (6): 681-92. [PMID:10761933]

7. Conchon E, Anizon F, Aboab B, Golsteyn RM, Léonce S, Pfeiffer B, Prudhomme M. (2008) Synthesis, checkpoint kinase 1 inhibitory properties and in vitro antiproliferative activities of new pyrrolocarbazoles. Bioorg. Med. Chem., 16 (8): 4419-30. [PMID:18321713]

8. 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]

9. Feldman RI, Wu JM, Polokoff MA, Kochanny MJ, Dinter H, Zhu D, Biroc SL, Alicke B, Bryant J, Yuan S et al.. (2005) Novel small molecule inhibitors of 3-phosphoinositide-dependent kinase-1. J. Biol. Chem., 280 (20): 19867-74. [PMID:15772071]

10. 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]

11. Huang X, Cheng CC, Fischmann TO, Duca JS, Richards M, Tadikonda PK, Reddy PA, Zhao L, Siddiqui MA, Parry D et al.. (2013) Structure-based design and optimization of 2-aminothiazole-4-carboxamide as a new class of CHK1 inhibitors. Bioorg. Med. Chem. Lett., 23 (9): 2590-4. [PMID:23535330]

12. Jackson JR, Gilmartin A, Imburgia C, Winkler JD, Marshall LA, Roshak A. (2000) An indolocarbazole inhibitor of human checkpoint kinase (Chk1) abrogates cell cycle arrest caused by DNA damage. Cancer Res., 60 (3): 566-72. [PMID:10676638]

13. Jiang X, Zhao B, Britton R, Lim LY, Leong D, Sanghera JS, Zhou BB, Piers E, Andersen RJ, Roberge M. (2004) Inhibition of Chk1 by the G2 DNA damage checkpoint inhibitor isogranulatimide. Mol. Cancer Ther., 3 (10): 1221-7. [PMID:15486189]

14. King C, Diaz H, Barnard D, Barda D, Clawson D, Blosser W, Cox K, Guo S, Marshall M. (2014) Characterization and preclinical development of LY2603618: a selective and potent Chk1 inhibitor. Invest New Drugs, 32 (2): 213-26. [PMID:24114124]

15. 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]

16. Labroli M, Paruch K, Dwyer MP, Alvarez C, Keertikar K, Poker C, Rossman R, Duca JS, Fischmann TO, Madison V et al.. (2011) Discovery of pyrazolo[1,5-a]pyrimidine-based CHK1 inhibitors: a template-based approach--part 2. Bioorg. Med. Chem. Lett., 21 (1): 471-4. [PMID:21094607]

17. Lainchbury M, Matthews TP, McHardy T, Boxall KJ, Walton MI, Eve PD, Hayes A, Valenti MR, de Haven Brandon AK, Box G et al.. (2012) Discovery of 3-alkoxyamino-5-(pyridin-2-ylamino)pyrazine-2-carbonitriles as selective, orally bioavailable CHK1 inhibitors. J. Med. Chem., 55 (22): 10229-40. [PMID:23082860]

18. Lovering F, Kirincich S, Wang W, Combs K, Resnick L, Sabalski JE, Butera J, Liu J, Parris K, Telliez JB. (2009) Identification and SAR of squarate inhibitors of mitogen activated protein kinase-activated protein kinase 2 (MK-2). Bioorg. Med. Chem., 17 (9): 3342-51. [PMID:19364658]

19. Ni ZJ, Barsanti P, Brammeier N, Diebes A, Poon DJ, Ng S, Pecchi S, Pfister K, Renhowe PA, Ramurthy S et al.. (2006) 4-(Aminoalkylamino)-3-benzimidazole-quinolinones as potent CHK-1 inhibitors. Bioorg. Med. Chem. Lett., 16 (12): 3121-4. [PMID:16603354]

20. 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]

21. 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]

22. Reinhardt HC, Aslanian AS, Lees JA, Yaffe MB. (2007) p53-deficient cells rely on ATM- and ATR-mediated checkpoint signaling through the p38MAPK/MK2 pathway for survival after DNA damage. Cancer Cell, 11 (2): 175-89. [PMID:17292828]

23. Tao ZF, Chen Z, Bui MH, Kovar P, Johnson E, Bouska J, Zhang H, Rosenberg S, Sowin T, Lin NH. (2007) Macrocyclic ureas as potent and selective Chk1 inhibitors: an improved synthesis, kinome profiling, structure-activity relationships, and preliminary pharmacokinetics. Bioorg. Med. Chem. Lett., 17 (23): 6593-601. [PMID:17935989]

24. 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]

How to cite this page

CHK1 subfamily: checkpoint kinase 1. Last modified on 21/04/2017. Accessed on 08/04/2020. IUPHAR/BPS Guide to PHARMACOLOGY,