Details of the Drug Therapeutic Target (DTT)

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

• DTT Name: Mixed lineage kinase 1 (MAP3K9)
• Synonyms: PRKE1; Mitogen-activated protein kinase kinase kinase 9; MLK1
• Gene Name: MAP3K9
• DTT Type: Clinical trial target; [1]
• BioChemical Class: Kinase
• UniProt ID: M3K9_HUMAN
• TTD ID: T19760
• EC Number: EC 2.7.11.25
• Sequence:
  MEPSRALLGCLASAAAAAPPGEDGAGAGAEEEEEEEEEAAAAVGPGELGCDAPLPYWTAV
  FEYEAAGEDELTLRLGDVVEVLSKDSQVSGDEGWWTGQLNQRVGIFPSNYVTPRSAFSSR
  CQPGGEDPSCYPPIQLLEIDFAELTLEEIIGIGGFGKVYRAFWIGDEVAVKAARHDPDED
  ISQTIENVRQEAKLFAMLKHPNIIALRGVCLKEPNLCLVMEFARGGPLNRVLSGKRIPPD
  ILVNWAVQIARGMNYLHDEAIVPIIHRDLKSSNILILQKVENGDLSNKILKITDFGLARE
  WHRTTKMSAAGTYAWMAPEVIRASMFSKGSDVWSYGVLLWELLTGEVPFRGIDGLAVAYG
  VAMNKLALPIPSTCPEPFAKLMEDCWNPDPHSRPSFTNILDQLTTIEESGFFEMPKDSFH
  CLQDNWKHEIQEMFDQLRAKEKELRTWEEELTRAALQQKNQEELLRRREQELAEREIDIL
  ERELNIIIHQLCQEKPRVKKRKGKFRKSRLKLKDGNRISLPSDFQHKFTVQASPTMDKRK
  SLINSRSSPPASPTIIPRLRAIQLTPGESSKTWGRSSVVPKEEGEEEEKRAPKKKGRTWG
  PGTLGQKELASGDEGSPQRREKANGLSTPSESPHFHLGLKSLVDGYKQWSSSAPNLVKGP
  RSSPALPGFTSLMEMEDEDSEGPGSGESRLQHSPSQSYLCIPFPRGEDGDGPSSDGIHEE
  PTPVNSATSTPQLTPTNSLKRGGAHHRRCEVALLGCGAVLAATGLGFDLLEAGKCQLLPL
  EEPEPPAREEKKRREGLFQRSSRPRRSTSPPSRKLFKKEEPMLLLGDPSASLTLLSLSSI
  SECNSTRSLLRSDSDEIVVYEMPVSPVEAPPLSPCTHNPLVNVRVERFKRDPNQSLTPTH
  VTLTTPSQPSSHRRTPSDGALKPETLLASRSPSSNGLSPSPGAGMLKTPSPSRDPGEFPR
  LPDPNVVFPPTPRRWNTQQDSTLERPKTLEFLPRPRPSANRQRLDPWWFVSPSHARSTSP
  ANSSSTETPSNLDSCFASSSSTVEERPGLPALLPFQAGPLPPTERTLLDLDAEGQSQDST
  VPLCRAELNTHRPAPYEIQQEFWS
• Function: Plays an important role in the cascades of cellular responses evoked by changes in the environment. Once activated, acts as an upstream activator of the MKK/JNK signal transduction cascade through the phosphorylation of MAP2K4/MKK4 and MAP2K7/MKK7 which in turn activate the JNKs. The MKK/JNK signaling pathway regulates stress response via activator protein-1 (JUN) and GATA4 transcription factors. Plays also a role in mitochondrial death signaling pathway, including the release cytochrome c, leading to apoptosis. Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway.

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
CEP1347	DMXCD69	Asthma	CA23	Phase 2/3	[1]

3 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
CEP-5104	DMV43GY	Discovery agent	N.A.	Investigative	[2]
CEP-6331	DMNXBTD	Discovery agent	N.A.	Investigative	[2]
URMC-099	DMCJXWK	Discovery agent	N.A.	Investigative	[3]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Asthma	CA23	Nasal and bronchial airway	9.49E-06	0.48	0.76

References

• [1] Pharmacological inhibitors of MAPK pathways. Trends Pharmacol Sci. 2002 Jan;23(1):40-5.
• [2] Mixed-lineage kinase 1 and mixed-lineage kinase 3 subtype-selective dihydronaphthyl[3,4-a]pyrrolo[3,4-c]carbazole-5-ones: optimization, mixed-linea... J Med Chem. 2008 Sep 25;51(18):5680-9.
• [3] Discovery, synthesis, and characterization of an orally bioavailable, brain penetrant inhibitor of mixed lineage kinase 3. J Med Chem. 2013 Oct 24;56(20):8032-48.