Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTETX6Q)

• DTT Name: Mixed lineage kinase 3 (MAP3K11)
• Synonyms: Src-homology 3 domain-containing proline-rich kinase; SPRK; SH3 domain-containing proline-rich kinase; Protein-tyrosine kinase PTK1; PTK1; Mixed-lineage protein kinase 3; Mitogen-activated protein kinase kinase kinase 11; MLK3
• Gene Name: MAP3K11
• DTT Type: Literature-reported target; [1]
• BioChemical Class: Kinase
• UniProt ID: M3K11_HUMAN
• TTD ID: T12126
• EC Number: EC 2.7.11.25
• Sequence:
  MEPLKSLFLKSPLGSWNGSGSGGGGGGGGGRPEGSPKAAGYANPVWTALFDYEPSGQDEL
  ALRKGDRVEVLSRDAAISGDEGWWAGQVGGQVGIFPSNYVSRGGGPPPCEVASFQELRLE
  EVIGIGGFGKVYRGSWRGELVAVKAARQDPDEDISVTAESVRQEARLFAMLAHPNIIALK
  AVCLEEPNLCLVMEYAAGGPLSRALAGRRVPPHVLVNWAVQIARGMHYLHCEALVPVIHR
  DLKSNNILLLQPIESDDMEHKTLKITDFGLAREWHKTTQMSAAGTYAWMAPEVIKASTFS
  KGSDVWSFGVLLWELLTGEVPYRGIDCLAVAYGVAVNKLTLPIPSTCPEPFAQLMADCWA
  QDPHRRPDFASILQQLEALEAQVLREMPRDSFHSMQEGWKREIQGLFDELRAKEKELLSR
  EEELTRAAREQRSQAEQLRRREHLLAQWELEVFERELTLLLQQVDRERPHVRRRRGTFKR
  SKLRARDGGERISMPLDFKHRITVQASPGLDRRRNVFEVGPGDSPTFPRFRAIQLEPAEP
  GQAWGRQSPRRLEDSSNGERRACWAWGPSSPKPGEAQNGRRRSRMDEATWYLDSDDSSPL
  GSPSTPPALNGNPPRPSLEPEEPKRPVPAERGSSSGTPKLIQRALLRGTALLASLGLGRD
  LQPPGGPGRERGESPTTPPTPTPAPCPTEPPPSPLICFSLKTPDSPPTPAPLLLDLGIPV
  GQRSAKSPRREEEPRGGTVSPPPGTSRSAPGTPGTPRSPPLGLISRPRPSPLRSRIDPWS
  FVSAGPRPSPLPSPQPAPRRAPWTLFPDSDPFWDSPPANPFQGGPQDCRAQTKDMGAQAP
  WVPEAGP
• Function: Required for serum-stimulated cell proliferation and for mitogen and cytokine activation of MAPK14 (p38), MAPK3 (ERK) and MAPK8 (JNK1) through phosphorylation and activation of MAP2K4/MKK4 and MAP2K7/MKK7. Plays a role in mitogen-stimulated phosphorylation and activation of BRAF, but does not phosphorylate BRAF directly. Influences microtubule organization during the cell cycle. Activates the JUN N-terminal pathway.
• Reactome Pathway:
  Signaling by moderate kinase activity BRAF mutants (R-HSA-6802946)
  Paradoxical activation of RAF signaling by kinase inactive BRAF (R-HSA-6802955)
  CDC42 GTPase cycle (R-HSA-9013148)
  RHOG GTPase cycle (R-HSA-9013408)
  RHOV GTPase cycle (R-HSA-9013424)
  Signaling downstream of RAS mutants (R-HSA-9649948)
  RAF activation (R-HSA-5673000)

Molecular Interaction Atlas (MIA) of This DTT

5 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]
CEP1349	DMOAZX5	Discovery agent	N.A.	Investigative	[3]
PMID24044867C8	DML4KMP	Discovery agent	N.A.	Investigative	[1]
URMC-099	DMCJXWK	Discovery agent	N.A.	Investigative	[1]

References

• [1] 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.
• [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] Pharmacological inhibitors of MAPK pathways. Trends Pharmacol Sci. 2002 Jan;23(1):40-5.