Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TT6NI13)

• DTT Name: MEK kinase kinase 4 (MAP4K4)
• Synonyms: Nckinteracting kinase; Nck-interacting kinase; Mitogenactivated protein kinase kinase kinase kinase 4; Mitogen-activated protein kinase kinase kinase kinase 4; MEKKK 4; MAPK/ERK kinase kinase kinase 4; KIAA0687; HPK/GCKlike kinase HGK; HPK/GCK-like kinase HGK; HGK
• Gene Name: MAP4K4
• DTT Type: Patented-recorded target; [1]
• BioChemical Class: Kinase
• UniProt ID: M4K4_HUMAN
• TTD ID: T71367
• EC Number: EC 2.7.11.1
• Sequence:
  MANDSPAKSLVDIDLSSLRDPAGIFELVEVVGNGTYGQVYKGRHVKTGQLAAIKVMDVTE
  DEEEEIKLEINMLKKYSHHRNIATYYGAFIKKSPPGHDDQLWLVMEFCGAGSITDLVKNT
  KGNTLKEDWIAYISREILRGLAHLHIHHVIHRDIKGQNVLLTENAEVKLVDFGVSAQLDR
  TVGRRNTFIGTPYWMAPEVIACDENPDATYDYRSDLWSCGITAIEMAEGAPPLCDMHPMR
  ALFLIPRNPPPRLKSKKWSKKFFSFIEGCLVKNYMQRPSTEQLLKHPFIRDQPNERQVRI
  QLKDHIDRTRKKRGEKDETEYEYSGSEEEEEEVPEQEGEPSSIVNVPGESTLRRDFLRLQ
  QENKERSEALRRQQLLQEQQLREQEEYKRQLLAERQKRIEQQKEQRRRLEEQQRREREAR
  RQQEREQRRREQEEKRRLEELERRRKEEEERRRAEEEKRRVEREQEYIRRQLEEEQRHLE
  VLQQQLLQEQAMLLECRWREMEEHRQAERLQRQLQQEQAYLLSLQHDHRRPHPQHSQQPP
  PPQQERSKPSFHAPEPKAHYEPADRAREVEDRFRKTNHSSPEAQSKQTGRVLEPPVPSRS
  ESFSNGNSESVHPALQRPAEPQVPVRTTSRSPVLSRRDSPLQGSGQQNSQAGQRNSTSIE
  PRLLWERVEKLVPRPGSGSSSGSSNSGSQPGSHPGSQSGSGERFRVRSSSKSEGSPSQRL
  ENAVKKPEDKKEVFRPLKPADLTALAKELRAVEDVRPPHKVTDYSSSSEESGTTDEEDDD
  VEQEGADESTSGPEDTRAASSLNLSNGETESVKTMIVHDDVESEPAMTPSKEGTLIVRQT
  QSASSTLQKHKSSSSFTPFIDPRLLQISPSSGTTVTSVVGFSCDGMRPEAIRQDPTRKGS
  VVNVNPTNTRPQSDTPEIRKYKKRFNSEILCAALWGVNLLVGTESGLMLLDRSGQGKVYP
  LINRRRFQQMDVLEGLNVLVTISGKKDKLRVYYLSWLRNKILHNDPEVEKKQGWTTVGDL
  EGCVHYKVVKYERIKFLVIALKSSVEVYAWAPKPYHKFMAFKSFGELVHKPLLVDLTVEE
  GQRLKVIYGSCAGFHAVDVDSGSVYDIYLPTHIQCSIKPHAIIILPNTDGMELLVCYEDE
  GVYVNTYGRITKDVVLQWGEMPTSVAYIRSNQTMGWGEKAIEIRSVETGHLDGVFMHKRA
  QRLKFLCERNDKVFFASVRSGGSSQVYFMTLGRTSLLSW
• Function: Appears to act upstream of the JUN N-terminal pathway. Phosphorylates SMAD1 on Thr-322. Serine/threonine kinase that may play a role in the response to environmental stress and cytokines such as TNF-alpha.
• KEGG Pathway: MAPK signaling pathway (hsa04010)
• Reactome Pathway: Oxidative Stress Induced Senescence (R-HSA-2559580)

Molecular Interaction Atlas (MIA) of This DTT

3 Patented Agent(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
6-Phenylquinazolin-4-amine	DMV5XR7	N. A.	N. A.	Patented	[2]
BDBM50011552	DMW5SD6	N. A.	N. A.	Patented	[2]
BDBM50011553	DMHNYQU	N. A.	N. A.	Patented	[2]

2 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
PMID23312943C21	DMOJ8QR	Discovery agent	N.A.	Investigative	[1]
PMID24673130C26	DM2HVU8	Discovery agent	N.A.	Investigative	[3]

References

• [1] Optimization of highly selective 2,4-diaminopyrimidine-5-carboxamide inhibitors of Sky kinase. Bioorg Med Chem Lett. 2013 Feb 15;23(4):1051-5.
• [2] Aminoquinazoline and pyridopyrimidine derivatives. US9592235.
• [3] Discovery of selective 4-Amino-pyridopyrimidine inhibitors of MAP4K4 using fragment-based lead identification and optimization. J Med Chem. 2014 Apr 24;57(8):3484-93.