Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTOHEU0N)

• DOT Name: Wee1-like protein kinase
• Synonyms: WEE1hu; EC 2.7.10.2; Wee1A kinase
• Gene Name: WEE1
• UniProt ID: WEE1_HUMAN
• PDB ID: 1X8B; 2IN6; 2IO6; 2Z2W; 3BI6; 3BIZ; 3CQE; 3CR0; 5V5Y; 5VC3; 5VC4; 5VC5; 5VC6; 5VD2; 5VD4; 5VD5; 5VD7; 5VD8; 5VD9; 5VDA; 7N3U; 8BJU
• EC Number: 2.7.10.2
• Pfam ID: PF00069
• Sequence:
  MSFLSRQQPPPPRRAGAACTLRQKLIFSPCSDCEEEEEEEEEEGSGHSTGEDSAFQEPDS
  PLPPARSPTEPGPERRRSPGPAPGSPGELEEDLLLPGACPGADEAGGGAEGDSWEEEGFG
  SSSPVKSPAAPYFLGSSFSPVRCGGPGDASPRGCGARRAGEGRRSPRPDHPGTPPHKTFR
  KLRLFDTPHTPKSLLSKARGIDSSSVKLRGSSLFMDTEKSGKREFDVRQTPQVNINPFTP
  DSLLLHSSGQCRRRKRTYWNDSCGEDMEASDYELEDETRPAKRITITESNMKSRYTTEFH
  ELEKIGSGEFGSVFKCVKRLDGCIYAIKRSKKPLAGSVDEQNALREVYAHAVLGQHSHVV
  RYFSAWAEDDHMLIQNEYCNGGSLADAISENYRIMSYFKEAELKDLLLQVGRGLRYIHSM
  SLVHMDIKPSNIFISRTSIPNAASEEGDEDDWASNKVMFKIGDLGHVTRISSPQVEEGDS
  RFLANEVLQENYTHLPKADIFALALTVVCAAGAEPLPRNGDQWHEIRQGRLPRIPQVLSQ
  EFTELLKVMIHPDPERRPSAMALVKHSVLLSASRKSAEQLRIELNAEKFKNSLLQKELKK
  AQMAKAAAEERALFTDRMATRSTTQSNRTSRLIGKKMNRSVSLTIY
• 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.
• KEGG Pathway:
  Cell cycle (hsa04110)
  Human immunodeficiency virus 1 infection (hsa05170)
• Reactome Pathway:
  Cyclin E associated events during G1/S transition (R-HSA-69202)
  Cyclin A/B1/B2 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 DOT

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Wee1-like protein kinase decreases the response to substance of Cisplatin.	[36]
Topotecan	DMP6G8T	Approved	Wee1-like protein kinase affects the response to substance of Topotecan.	[37]

9 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Wee1-like protein kinase.	[1]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the phosphorylation of Wee1-like protein kinase.	[5]
Temozolomide	DMKECZD	Approved	Temozolomide increases the phosphorylation of Wee1-like protein kinase.	[8]
Bortezomib	DMNO38U	Approved	Bortezomib increases the ubiquitination of Wee1-like protein kinase.	[13]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the phosphorylation of Wee1-like protein kinase.	[8]
MK-1775	DM3WDZ5	Phase 2	MK-1775 decreases the phosphorylation of Wee1-like protein kinase.	[18]
INCB057643	DMG65CV	Phase 1/2	INCB057643 decreases the phosphorylation of Wee1-like protein kinase.	[19]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Wee1-like protein kinase.	[27]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of Wee1-like protein kinase.	[30]

31 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Wee1-like protein kinase.	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Wee1-like protein kinase.	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Wee1-like protein kinase.	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Wee1-like protein kinase.	[6]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Wee1-like protein kinase.	[7]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide affects the expression of Wee1-like protein kinase.	[9]
Marinol	DM70IK5	Approved	Marinol increases the expression of Wee1-like protein kinase.	[10]
Demecolcine	DMCZQGK	Approved	Demecolcine decreases the expression of Wee1-like protein kinase.	[11]
Cannabidiol	DM0659E	Approved	Cannabidiol decreases the expression of Wee1-like protein kinase.	[12]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the expression of Wee1-like protein kinase.	[14]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol increases the expression of Wee1-like protein kinase.	[15]
Romidepsin	DMT5GNL	Approved	Romidepsin decreases the expression of Wee1-like protein kinase.	[16]
AC220	DM8Y4JS	Approved	AC220 decreases the expression of Wee1-like protein kinase.	[16]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Wee1-like protein kinase.	[16]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene affects the expression of Wee1-like protein kinase.	[3]
Napabucasin	DMDZ6Q3	Phase 3	Napabucasin decreases the expression of Wee1-like protein kinase.	[17]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Wee1-like protein kinase.	[20]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Wee1-like protein kinase.	[21]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Wee1-like protein kinase.	[22]
Mivebresib	DMCPF90	Phase 1	Mivebresib decreases the expression of Wee1-like protein kinase.	[23]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Wee1-like protein kinase.	[24]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of Wee1-like protein kinase.	[25]
Dioscin	DM5H2W9	Preclinical	Dioscin increases the expression of Wee1-like protein kinase.	[26]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Wee1-like protein kinase.	[28]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Wee1-like protein kinase.	[29]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A decreases the expression of Wee1-like protein kinase.	[31]
acrolein	DMAMCSR	Investigative	acrolein increases the expression of Wee1-like protein kinase.	[32]
ELLAGIC ACID	DMX8BS5	Investigative	ELLAGIC ACID decreases the expression of Wee1-like protein kinase.	[33]
Morin	DM2OGZ5	Investigative	Morin increases the expression of Wee1-like protein kinase.	[34]
LICOAGROCHACONE A	DMWY0TN	Investigative	LICOAGROCHACONE A increases the expression of Wee1-like protein kinase.	[35]
RGFP966	DME9T0A	Investigative	RGFP966 decreases the expression of Wee1-like protein kinase.	[16]

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