Target Information

Target General Infomation
Target ID
T69991
Former ID
TTDC00256
Target Name
Wee1-like protein kinase
Gene Name
WEE1
Synonyms
WEE1hu; Wee1A kinase; WEE1
Target Type
Clinical Trial
Disease Ovarian cancer [ICD9: 183; ICD10: C56]
Function
Acts as a negative regulator of entry into mitosis (G2 to M transition) by protecting the nucleus from cytoplasmically activated cyclin B1-complexed CDK1 before the onset of mitosis by mediating phosphorylation of CDK1 on 'Tyr-15'. Specifically phosphorylates and inactivates cyclin B1-complexed CDK1 reaching a maximum during G2 phase and a minimum as cells enter M phase. Phosphorylation of cyclin B1-CDK1 occurs exclusively on 'Tyr-15' and phosphorylation of monomeric CDK1 does not occur. Its activity increases during S and G2 phases and decreases at M phase when it is hyperphosphorylated. A correlated decrease in protein level occurs at M/G1 phase, probably due to its degradation.
BioChemical Class
Kinase
Target Validation
T69991
UniProt ID
P30291
EC Number
EC 2.7.10.2
Sequence
MSFLSRQQPPPPRRAGAACTLRQKLIFSPCSDCEEEEEEEEEEGSGHSTGEDSAFQEPDS
PLPPARSPTEPGPERRRSPGPAPGSPGELEEDLLLPGACPGADEAGGGAEGDSWEEEGFG
SSSPVKSPAAPYFLGSSFSPVRCGGPGDASPRGCGARRAGEGRRSPRPDHPGTPPHKTFR
KLRLFDTPHTPKSLLSKARGIDSSSVKLRGSSLFMDTEKSGKREFDVRQTPQVNINPFTP
DSLLLHSSGQCRRRKRTYWNDSCGEDMEASDYELEDETRPAKRITITESNMKSRYTTEFH
ELEKIGSGEFGSVFKCVKRLDGCIYAIKRSKKPLAGSVDEQNALREVYAHAVLGQHSHVV
RYFSAWAEDDHMLIQNEYCNGGSLADAISENYRIMSYFKEAELKDLLLQVGRGLRYIHSM
SLVHMDIKPSNIFISRTSIPNAASEEGDEDDWASNKVMFKIGDLGHVTRISSPQVEEGDS
RFLANEVLQENYTHLPKADIFALALTVVCAAGAEPLPRNGDQWHEIRQGRLPRIPQVLSQ
EFTELLKVMIHPDPERRPSAMALVKHSVLLSASRKSAEQLRIELNAEKFKNSLLQKELKK
AQMAKAAAEERALFTDRMATRSTTQSNRTSRLIGKKMNRSVSLTIY
Drugs and Mode of Action
Drug(s) MK-1775 Drug Info Phase 2 Ovarian cancer [531656], [542678]
Inhibitor 9-hydroxypyrrolo[3,4-c]carbazole-1,3(2H,6H)-dione Drug Info [529785]
MK-1775 Drug Info [537429], [549718]
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM)
TEP EXP Info
Pathways
KEGG Pathway Cell cycle
NetPath Pathway TGF_beta_Receptor Signaling Pathway
Pathway Interaction Database PLK1 signaling events
Reactome Polo-like kinase mediated events
Cyclin E associated events during G1/S transition
Cyclin A/B1 associated events during G2/M transition
G2/M DNA replication checkpoint
Cdk2-associated events at S phase entry
Cdk1 complex
Factors involved in megakaryocyte development and platelet production
WikiPathways G1 to S cell cycle control
S Phase
Retinoblastoma (RB) in Cancer
Integrated Breast Cancer Pathway
Mitotic G2-G2/M phases
Mitotic G1-G1/S phases
Factors involved in megakaryocyte development and platelet production
Cell Cycle
Cell Cycle Checkpoints
References
Ref 531656Targeting radiation-induced G(2) checkpoint activation with the Wee-1 inhibitor MK-1775 in glioblastoma cell lines. Mol Cancer Ther. 2011 Dec;10(12):2405-14.
Ref 542678(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7702).
Ref 529785Eur J Med Chem. 2009 Apr;44(4):1383-95. Epub 2008 Sep 30.Receptor-based 3D-QSAR studies of checkpoint Wee1 kinase inhibitors.
Ref 537429Discovery of gene expression-based pharmacodynamic biomarker for a p53 context-specific anti-tumor drug Wee1 inhibitor. Mol Cancer. 2009 Jun 8;8:34.
Ref 549718A novel c-Met inhibitor, MK8033, synergizes with carboplatin plus paclitaxel to inhibit ovarian cancer cell growth. Oncol Rep. 2013 May;29(5):2011-8.

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