Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTP7EGM)

• DTT Name: Dual specificity protein kinase TTK (MPS1)
• Synonyms: Tyrosine threonine kinase; Phosphotyrosine picked threonine-protein kinase; PYT; MPS1L1
• Gene Name: TTK
• DTT Type: Clinical trial target; [1]
• BioChemical Class: Kinase
• UniProt ID: TTK_HUMAN
• TTD ID: T74977
• EC Number: EC 2.7.12.1
• Sequence:
  MESEDLSGRELTIDSIMNKVRDIKNKFKNEDLTDELSLNKISADTTDNSGTVNQIMMMAN
  NPEDWLSLLLKLEKNSVPLSDALLNKLIGRYSQAIEALPPDKYGQNESFARIQVRFAELK
  AIQEPDDARDYFQMARANCKKFAFVHISFAQFELSQGNVKKSKQLLQKAVERGAVPLEML
  EIALRNLNLQKKQLLSEEEKKNLSASTVLTAQESFSGSLGHLQNRNNSCDSRGQTTKARF
  LYGENMPPQDAEIGYRNSLRQTNKTKQSCPFGRVPVNLLNSPDCDVKTDDSVVPCFMKRQ
  TSRSECRDLVVPGSKPSGNDSCELRNLKSVQNSHFKEPLVSDEKSSELIITDSITLKNKT
  ESSLLAKLEETKEYQEPEVPESNQKQWQSKRKSECINQNPAASSNHWQIPELARKVNTEQ
  KHTTFEQPVFSVSKQSPPISTSKWFDPKSICKTPSSNTLDDYMSCFRTPVVKNDFPPACQ
  LSTPYGQPACFQQQQHQILATPLQNLQVLASSSANECISVKGRIYSILKQIGSGGSSKVF
  QVLNEKKQIYAIKYVNLEEADNQTLDSYRNEIAYLNKLQQHSDKIIRLYDYEITDQYIYM
  VMECGNIDLNSWLKKKKSIDPWERKSYWKNMLEAVHTIHQHGIVHSDLKPANFLIVDGML
  KLIDFGIANQMQPDTTSVVKDSQVGTVNYMPPEAIKDMSSSRENGKSKSKISPKSDVWSL
  GCILYYMTYGKTPFQQIINQISKLHAIIDPNHEIEFPDIPEKDLQDVLKCCLKRDPKQRI
  SIPELLAHPYVQIQTHPVNQMAKGTTEEMKYVLGQLVGLNSPNSILKAAKTLYEHYSGGE
  SHNSSSSKTFEKKRGKK
• Function: Probably associated with cell proliferation. Essential for chromosome alignment by enhancing AURKB activity (via direct CDCA8 phosphorylation) at the centromere, and for the mitotic checkpoint. Phosphorylates proteins on serine, threonine, and tyrosine.
• KEGG Pathway: Cell cycle (hsa04110)

Molecular Interaction Atlas (MIA) of This DTT

3 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
BAY1161909	DMUK6YM	Solid tumour/cancer	2A00-2F9Z	Phase 1	[1]
BOS172722	DMU790L	Solid tumour/cancer	2A00-2F9Z	Phase 1	[2]
CFI-402257	DMH701Q	Solid tumour/cancer	2A00-2F9Z	Phase 1	[3]

3 Patented Agent(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Tricyclic isoxazoloquinazoline derivative 2	DMH4TY1	N. A.	N. A.	Patented	[4]
Tricyclic isoxazoloquinazoline derivative 3	DML2PWF	N. A.	N. A.	Patented	[4]
Tricyclic isoxazoloquinazoline derivative 4	DM8VIM4	N. A.	N. A.	Patented	[4]

2 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
2,6-Dihydroanthra/1,9-Cd/Pyrazol-6-One	DMDN12L	Discovery agent	N.A.	Investigative	[5]
GNE-7915	DMYWM56	Discovery agent	N.A.	Investigative	[6]

References

• [1] National Cancer Institute Drug Dictionary (drug id 761238).
• [2] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [3] Functional characterization of CFI-402257, a potent and selective Mps1/TTK kinase inhibitor, for the treatment of cancer. Proc Natl Acad Sci U S A. 2017 Mar 21;114(12):3127-3132.
• [4] Protein kinase R(PKR)-like endoplasmic reticulum kinase (PERK) inhibitors: a patent review (2010-2015).Expert Opin Ther Pat. 2017 Jan;27(1):37-48.
• [5] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
• [6] Discovery of highly potent, selective, and brain-penetrant aminopyrazole leucine-rich repeat kinase 2 (LRRK2) small molecule inhibitors. J Med Chem. 2014 Feb 13;57(3):921-36.