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
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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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.
KEGG Pathway
MAPK signaling pathway (mmu04010 )
Non-alcoholic fatty liver disease (NAFLD) (mmu04932 )
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

Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas 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]
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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.