Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTR0SWN)

• DTT Name: M-phase inducer phosphatase 2 (MPIP2)
• Synonyms: Dual specificity phosphatase Cdc25B; Cdc25B phosphatase; CDC25HU2
• Gene Name: CDC25B
• DTT Type: Clinical trial target; [1]
• BioChemical Class: Phosphoric monoester hydrolase
• UniProt ID: MPIP2_HUMAN
• TTD ID: T46365
• EC Number: EC 3.1.3.48
• Sequence:
  MEVPQPEPAPGSALSPAGVCGGAQRPGHLPGLLLGSHGLLGSPVRAAASSPVTTLTQTMH
  DLAGLGSETPKSQVGTLLFRSRSRLTHLSLSRRASESSLSSESSESSDAGLCMDSPSPMD
  PHMAEQTFEQAIQAASRIIRNEQFAIRRFQSMPVRLLGHSPVLRNITNSQAPDGRRKSEA
  GSGAASSSGEDKENDGFVFKMPWKPTHPSSTHALAEWASRREAFAQRPSSAPDLMCLSPD
  RKMEVEELSPLALGRFSLTPAEGDTEEDDGFVDILESDLKDDDAVPPGMESLISAPLVKT
  LEKEEEKDLVMYSKCQRLFRSPSMPCSVIRPILKRLERPQDRDTPVQNKRRRSVTPPEEQ
  QEAEEPKARVLRSKSLCHDEIENLLDSDHRELIGDYSKAFLLQTVDGKHQDLKYISPETM
  VALLTGKFSNIVDKFVIVDCRYPYEYEGGHIKTAVNLPLERDAESFLLKSPIAPCSLDKR
  VILIFHCEFSSERGPRMCRFIRERDRAVNDYPSLYYPEMYILKGGYKEFFPQHPNFCEPQ
  DYRPMNHEAFKDELKTFRLKTRSWAGERSRRELCSRLQDQ
• Function: Required for G2/M phases of the cell cycle progression and abscission during cytokinesis in a ECT2-dependent manner. Directly dephosphorylates CDK1 and stimulates its kinase activity. The three isoforms seem to have a different level of activity. Tyrosine protein phosphatase which functions as a dosage-dependent inducer of mitotic progression.
• KEGG Pathway:
  MAPK signaling pathway (hsa04010)
  Cell cycle (hsa04110)
  Progesterone-mediated oocyte maturation (hsa04914)
  MicroRNAs in cancer (hsa05206)
• Reactome Pathway:
  Cyclin A/B1 associated events during G2/M transition (R-HSA-69273)
  Cyclin A (R-HSA-69656)
  Cyclin B2 mediated events (R-HSA-157881)

Molecular Interaction Atlas (MIA) of This DTT

1 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Avastin+/-Tarceva	DMA86FL	Non-small-cell lung cancer	2C25.Y	Phase 3	[1]

1 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
MX-7065	DMP26BW	Solid tumour/cancer	2A00-2F9Z	Terminated	[2]

15 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
2-Sulfhydryl-Ethanol	DMJBO3D	Discovery agent	N.A.	Investigative	[3]
3-isopropyl-4-(phenylamino)naphthalene-1,2-dione	DMHAJ6W	Discovery agent	N.A.	Investigative	[4]
3-isopropyl-4-(phenylthio)naphthalene-1,2-dione	DMJZEMB	Discovery agent	N.A.	Investigative	[4]
3-isopropyl-4-phenylnaphthalene-1,2-dione	DMYZCWX	Discovery agent	N.A.	Investigative	[4]
4-(p-toluidino)-3-isopropylnaphthalene-1,2-dione	DMQA0EJ	Discovery agent	N.A.	Investigative	[4]
4-ethoxynaphthalene-1,2-dione	DMUN7KC	Discovery agent	N.A.	Investigative	[1]
5,6,7,8-tetrahydroanthracene-1,4-dione	DMIQAO9	Discovery agent	N.A.	Investigative	[1]
6,7-dibromoquinoline-5,8-dione	DMDO083	Discovery agent	N.A.	Investigative	[5]
ADOCIAQUINONE B	DMPOU86	Discovery agent	N.A.	Investigative	[5]
ANTHRAQUINONE	DM29I0Y	Discovery agent	N.A.	Investigative	[1]
Cysteine Sulfenic Acid	DM4GZUJ	N. A.	N. A.	Investigative	[6]
Cysteinesulfonic Acid	DMXI8FP	Discovery agent	N.A.	Investigative	[3]
Double Oxidized Cysteine	DM6TU84	Discovery agent	N.A.	Investigative	[3]
Methyl Mercury Ion	DM6YEW4	Discovery agent	N.A.	Investigative	[3]
NSC-95397	DMX0TAM	Discovery agent	N.A.	Investigative	[5]

References

• [1] Bioactivities of simplified adociaquinone B and naphthoquinone derivatives against Cdc25B, MKP-1, and MKP-3 phosphatases. Bioorg Med Chem. 2009 Mar 15;17(6):2276-81.
• [2] Handbook of Assay Development in Drug Discovery, Lisa K. Minor, 2013. Page(11).
• [3] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
• [4] Synthesis of miltirone analogues as inhibitors of Cdc25 phosphatases. Bioorg Med Chem Lett. 2006 Apr 1;16(7):1905-8.
• [5] Novel naphthoquinone and quinolinedione inhibitors of CDC25 phosphatase activity with antiproliferative properties. Bioorg Med Chem. 2008 Oct 1;16(19):9040-9.
• [6] DrugBank 3.0: a comprehensive resource for 'omics' research on drugs. Nucleic Acids Res. 2011 Jan;39(Database issue):D1035-41.