Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTLZS4Q)

• DTT Name: M-phase inducer phosphatase 1 (MPIP1)
• Synonyms: Dual specificity phosphatase Cdc25A; Cdc25A phosphatase
• Gene Name: CDC25A
• DTT Type: Literature-reported target; [1]
• BioChemical Class: Phosphoric monoester hydrolase
• UniProt ID: MPIP1_HUMAN
• TTD ID: T30823
• EC Number: EC 3.1.3.48
• Sequence:
  MELGPEPPHRRRLLFACSPPPASQPVVKALFGASAAGGLSPVTNLTVTMDQLQGLGSDYE
  QPLEVKNNSNLQRMGSSESTDSGFCLDSPGPLDSKENLENPMRRIHSLPQKLLGCSPALK
  RSHSDSLDHDIFQLIDPDENKENEAFEFKKPVRPVSRGCLHSHGLQEGKDLFTQRQNSAP
  ARMLSSNERDSSEPGNFIPLFTPQSPVTATLSDEDDGFVDLLDGENLKNEEETPSCMASL
  WTAPLVMRTTNLDNRCKLFDSPSLCSSSTRSVLKRPERSQEESPPGSTKRRKSMSGASPK
  ESTNPEKAHETLHQSLSLASSPKGTIENILDNDPRDLIGDFSKGYLFHTVAGKHQDLKYI
  SPEIMASVLNGKFANLIKEFVIIDCRYPYEYEGGHIKGAVNLHMEEEVEDFLLKKPIVPT
  DGKRVIVVFHCEFSSERGPRMCRYVRERDRLGNEYPKLHYPELYVLKGGYKEFFMKCQSY
  CEPPSYRPMHHEDFKEDLKKFRTKSRTWAGEKSKREMYSRLKKL
• Function: Directly dephosphorylates CDK1 and stimulates its kinase activity. Also dephosphorylates CDK2 in complex with cyclin E, in vitro. Tyrosine protein phosphatase which functions as a dosage-dependent inducer of mitotic progression.
• KEGG Pathway:
  Cell cycle (hsa04110)
  Progesterone-mediated oocyte maturation (hsa04914)
  MicroRNAs in cancer (hsa05206)
• Reactome Pathway:
  G0 and Early G1 (R-HSA-1538133)
  Polo-like kinase mediated events (R-HSA-156711)
  Cyclin B2 mediated events (R-HSA-157881)
  Activation of ATR in response to replication stress (R-HSA-176187)
  Cyclin E associated events during G1/S transition (R-HSA-69202)
  G1/S-Specific Transcription (R-HSA-69205)
  Cyclin A/B1 associated events during G2/M transition (R-HSA-69273)
  Ubiquitin Mediated Degradation of Phosphorylated Cdc25A (R-HSA-69601)
  Cyclin A (R-HSA-69656)
  E2F mediated regulation of DNA replication (R-HSA-113510)

Molecular Interaction Atlas (MIA) of This DTT

2 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	[1]
Ro 20-1724	DM0PSCF	Asthma	CA23	Terminated	[2]

10 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
(E)-2-(1-decyl-2-oxoindolin-3-ylidene)acetic acid	DMI146O	Discovery agent	N.A.	Investigative	[3]
(Z)-2-(1-decyl-2-oxoindolin-3-ylidene)acetic acid	DMKQ679	Discovery agent	N.A.	Investigative	[3]
1-dodecyl-1H-indole-2,3-dione	DMK6BWV	Discovery agent	N.A.	Investigative	[3]
2-(1-dodecyl-1H-indol-3-yl)acetic acid	DMF2XHZ	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]
3-isopropylnaphthalene-1,2-dione	DM46ID2	Discovery agent	N.A.	Investigative	[4]
4-(p-toluidino)-3-isopropylnaphthalene-1,2-dione	DMQA0EJ	Discovery agent	N.A.	Investigative	[4]
NSC-95397	DMX0TAM	Discovery agent	N.A.	Investigative	[5]

References

• [1] Handbook of Assay Development in Drug Discovery, Lisa K. Minor, 2013. Page(11).
• [2] Role of the Cdc25A phosphatase in human breast cancer. J Clin Invest. 2000 Sep;106(6):753-61.
• [3] Design and synthesis of N-alkyl oxindolylidene acetic acids as a new class of potent Cdc25A inhibitors. Bioorg Med Chem Lett. 2008 Jun 1;18(11):3350-3.
• [4] Synthesis of miltirone analogues as inhibitors of Cdc25 phosphatases. Bioorg Med Chem Lett. 2006 Apr 1;16(7):1905-8.
• [5] Structure-based de novo design and biochemical evaluation of novel Cdc25 phosphatase inhibitors. Bioorg Med Chem Lett. 2009 Aug 1;19(15):4330-4.