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WEE1 G2 checkpoint kinase

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Target not currently curated in GtoImmuPdb

Target id: 2278

Nomenclature: WEE1 G2 checkpoint kinase

Abbreviated Name: Wee1

Family: WEE family

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 646 11p15.4 WEE1 WEE1 G2 checkpoint kinase
Mouse - 646 7 E3 Wee1 WEE 1 homolog 1 (S. pombe)
Rat - 646 1q33 Wee1 WEE1 G2 checkpoint kinase
Previous and Unofficial Names Click here for help
WEE1 tyrosine kinase | Wee1A | WEE1 homolog (S. pombe) | wee 1 homolog (S. pombe)
Database Links Click here for help
Alphafold P30291 (Hs), P47810 (Mm), Q63802 (Rn)
BRENDA 2.7.10.2
ChEMBL Target CHEMBL5491 (Hs)
Ensembl Gene ENSG00000166483 (Hs), ENSMUSG00000031016 (Mm), ENSRNOG00000010017 (Rn)
Entrez Gene 7465 (Hs), 22390 (Mm), 308937 (Rn)
Human Protein Atlas ENSG00000166483 (Hs)
KEGG Enzyme 2.7.10.2
KEGG Gene hsa:7465 (Hs), mmu:22390 (Mm), rno:308937 (Rn)
OMIM 193525 (Hs)
Pharos P30291 (Hs)
RefSeq Nucleotide NM_003390 (Hs), NM_009516 (Mm), NM_001012742 (Rn)
RefSeq Protein NP_003381 (Hs), NP_033542 (Mm), NP_001012760 (Rn)
UniProtKB P30291 (Hs), P47810 (Mm), Q63802 (Rn)
Wikipedia WEE1 (Hs)
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  Structure of human Wee1A kinase: kinase domain complexed with inhibitor PD0407824.
PDB Id:  1X8B
Resolution:  1.81Å
Species:  Human
References:  5
Enzyme Reaction Click here for help
EC Number: 2.7.10.2

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
azenosertib Small molecule or natural product Ligand has a PDB structure Hs Inhibition 8.4 pIC50 4
⤷ pIC50 8.4 (IC50 3.9x10-9 M) [4]
adavosertib Small molecule or natural product Primary target of this compound Ligand has a PDB structure Hs Inhibition 8.3 pIC50 2
⤷ pIC50 8.3 (IC50 5.18x10-9 M) [2]
PD166285 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.6 pIC50 6
⤷ pIC50 7.6 (IC50 2.4x10-8 M) [6]
DiscoveRx KINOMEscan® screen Click here for help
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: 3,7
Key to terms and symbols Click column headers to sort
Target used in screen: WEE1
Ligand Sp. Type Action Value Parameter
PD-173955 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 7.2 pKd
fedratinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 6.4 pKd
bosutinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 6.3 pKd
tamatinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 6.1 pKd
sunitinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 6.0 pKd
dovitinib Small molecule or natural product Hs Inhibitor Inhibition 5.9 pKd
lestaurtinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 5.9 pKd
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 5.8 pKd
KW-2449 Small molecule or natural product Hs Inhibitor Inhibition 5.6 pKd
SB203580 Small molecule or natural product Immunopharmacology Ligand Hs Inhibitor Inhibition <5.5 pKd
Displaying the top 10 most potent ligands  View all ligands in screen »
EMD Millipore KinaseProfilerTM screen/Reaction Biology Kinase HotspotSM screen Click here for help
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
Key to terms and symbols Click column headers to sort
Target used in screen: nd/WEE1
Ligand Sp. Type Action % Activity remaining at 0.5µM % Activity remaining at 1µM % Activity remaining at 10µM
SB 218078 Small molecule or natural product Hs Inhibitor Inhibition 16.9
bosutinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 40.5
JAK3 inhibitor VI Small molecule or natural product Hs Inhibitor Inhibition 69.4
aminopurvalanol A Small molecule or natural product Hs Inhibitor Inhibition 70.8
PDK1/Akt/Flt dual pathway inhibitor Small molecule or natural product Hs Inhibitor Inhibition 70.9
MEK inhibitor I Small molecule or natural product Hs Inhibitor Inhibition 70.9
K-252a Small molecule or natural product Hs Inhibitor Inhibition 72.9
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 73.1
MEK1/2 inhibitor Small molecule or natural product Hs Inhibitor Inhibition 73.8
Tpl2 kinase inhibitor Small molecule or natural product Hs Inhibitor Inhibition 74.3
Displaying the top 10 most potent ligands  View all ligands in screen »

References

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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. AstraZeneca. AZD1775. Accessed on 11/09/2014. Modified on 11/09/2014. astrazeneca.com, http://openinnovation.astrazeneca.com/what-we-offer/compound/867-2/

3. 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]

4. Huang PQ, Boren BC, Hegde SG, Liu H, Unni AK, Abraham S, Hopkins CD, Paliwal S, Samatar AA, Li J et al.. (2021) Discovery of ZN-c3, a Highly Potent and Selective Wee1 Inhibitor Undergoing Evaluation in Clinical Trials for the Treatment of Cancer. J Med Chem, 64 (17): 13004-13024. [PMID:34423975]

5. Squire CJ, Dickson JM, Ivanovic I, Baker EN. (2005) Structure and inhibition of the human cell cycle checkpoint kinase, Wee1A kinase: an atypical tyrosine kinase with a key role in CDK1 regulation. Structure, 13 (4): 541-50. [PMID:15837193]

6. Wang Y, Li J, Booher RN, Kraker A, Lawrence T, Leopold WR, Sun Y. (2001) Radiosensitization of p53 mutant cells by PD0166285, a novel G(2) checkpoint abrogator. Cancer Res, 61 (22): 8211-7. [PMID:11719452]

7. 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

WEE family: WEE1 G2 checkpoint kinase. Last modified on 29/09/2021. Accessed on 18/04/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2278.