Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTJFOAL)

• DTT Name: Wee1-like protein kinase (WEE1)
• Synonyms: Wee1A kinase; WEE1hu
• Gene Name: WEE1
• DTT Type: Clinical trial target; [1]
• Related Disease:
  Ovarian cancer [ICD-11: 2C73]
  Uterine ligament/parametrium/uterine adnexa neoplasm [ICD-11: 2C72]
  Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• BioChemical Class: Kinase
• UniProt ID: WEE1_HUMAN
• TTD ID: T69991
• EC Number: EC 2.7.10.2
• Sequence:
  MSFLSRQQPPPPRRAGAACTLRQKLIFSPCSDCEEEEEEEEEEGSGHSTGEDSAFQEPDS
  PLPPARSPTEPGPERRRSPGPAPGSPGELEEDLLLPGACPGADEAGGGAEGDSWEEEGFG
  SSSPVKSPAAPYFLGSSFSPVRCGGPGDASPRGCGARRAGEGRRSPRPDHPGTPPHKTFR
  KLRLFDTPHTPKSLLSKARGIDSSSVKLRGSSLFMDTEKSGKREFDVRQTPQVNINPFTP
  DSLLLHSSGQCRRRKRTYWNDSCGEDMEASDYELEDETRPAKRITITESNMKSRYTTEFH
  ELEKIGSGEFGSVFKCVKRLDGCIYAIKRSKKPLAGSVDEQNALREVYAHAVLGQHSHVV
  RYFSAWAEDDHMLIQNEYCNGGSLADAISENYRIMSYFKEAELKDLLLQVGRGLRYIHSM
  SLVHMDIKPSNIFISRTSIPNAASEEGDEDDWASNKVMFKIGDLGHVTRISSPQVEEGDS
  RFLANEVLQENYTHLPKADIFALALTVVCAAGAEPLPRNGDQWHEIRQGRLPRIPQVLSQ
  EFTELLKVMIHPDPERRPSAMALVKHSVLLSASRKSAEQLRIELNAEKFKNSLLQKELKK
  AQMAKAAAEERALFTDRMATRSTTQSNRTSRLIGKKMNRSVSLTIY
• Function: 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. 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'.
• Reactome Pathway:
  Cyclin E associated events during G1/S transition (R-HSA-69202)
  Cyclin A/B1 associated events during G2/M transition (R-HSA-69273)
  G2/M DNA replication checkpoint (R-HSA-69478)
  Cyclin A (R-HSA-69656)
  Chk1/Chk2(Cds1) mediated inactivation of Cyclin B (R-HSA-75035)
  Factors involved in megakaryocyte development and platelet production (R-HSA-983231)
  Polo-like kinase mediated events (R-HSA-156711)

Molecular Interaction Atlas (MIA) of This DTT

2 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
MK-1775	DM3WDZ5	Ovarian cancer	2C73	Phase 2	[1], [2]
ZN-c3	DM4MSLY	Uterine serous carcinoma	2C72.1	Phase 2	[3]

1 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
9-hydroxypyrrolo[3,4-c]carbazole-1,3(2H,6H)-dione	DMGCX7E	Discovery agent	N.A.	Investigative	[4]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Ovarian cancer	2C82	Ovarian tissue	7.06E-07	1.06	4.21

References

• [1] A novel c-Met inhibitor, MK8033, synergizes with carboplatin plus paclitaxel to inhibit ovarian cancer cell growth. Oncol Rep. 2013 May;29(5):2011-8.
• [2] Discovery of gene expression-based pharmacodynamic biomarker for a p53 context-specific anti-tumor drug Wee1 inhibitor. Mol Cancer. 2009 Jun 8;8:34.
• [3] Clinical pipeline report, company report or official report of Zentalis Pharmaceuticals.
• [4] Receptor-based 3D-QSAR studies of checkpoint Wee1 kinase inhibitors. Eur J Med Chem. 2009 Apr;44(4):1383-95.