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mitogen-activated protein kinase kinase kinase 10

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Target id: 2070

Nomenclature: mitogen-activated protein kinase kinase kinase 10

Abbreviated Name: MLK2

Family: MLK subfamily

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 954 19q13.2 MAP3K10 mitogen-activated protein kinase kinase kinase 10
Mouse - 940 7 A3 Map3k10 mitogen-activated protein kinase kinase kinase 10
Rat - 942 1 q21 Map3k10 mitogen activated protein kinase kinase kinase 10
Previous and Unofficial Names Click here for help
mixed lineage kinase 2 | MKN28 kinase | MLK2 | MST
Database Links Click here for help
Alphafold Q02779 (Hs), Q66L42 (Mm)
BRENDA 2.7.11.25
ChEMBL Target CHEMBL2873 (Hs)
Ensembl Gene ENSG00000130758 (Hs), ENSMUSG00000040390 (Mm), ENSRNOG00000023521 (Rn)
Entrez Gene 4294 (Hs), 269881 (Mm), 308463 (Rn)
Human Protein Atlas ENSG00000130758 (Hs)
KEGG Enzyme 2.7.11.25
KEGG Gene hsa:4294 (Hs), mmu:269881 (Mm), rno:308463 (Rn)
OMIM 600137 (Hs)
Pharos Q02779 (Hs)
RefSeq Nucleotide NM_002446 (Hs), NM_001290528 (Mm), NM_001191621 (Rn)
RefSeq Protein NP_002437 (Hs), NP_001277457 (Mm), NP_001178550 (Rn)
UniProtKB Q02779 (Hs), Q66L42 (Mm)
Wikipedia MAP3K10 (Hs)
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of human mixed lineage kinase MAP3K10 SH3 domain
PDB Id:  2RF0
Resolution:  2.0Å
Species:  Human
References: 
Enzyme Reaction Click here for help
EC Number: 2.7.11.25

Download all structure-activity data for this target as a CSV file go icon to follow link

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
CEP-1347 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.3 – 8.7 pIC50 3-4
⤷ pIC50 7.3 – 8.7 (IC50 5.1x10-8 – 2x10-9 M) [3-4]
URMC-099 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 7.4 pIC50 3
⤷ pIC50 7.4 (IC50 4.2x10-8 M) [3]
DiscoveRx KINOMEscan® screen Click here for help
A screen of 72 inhibitors against 456 human kinases. Quantitative data were derived using DiscoveRx KINOMEscan® platform.
http://www.discoverx.com/services/drug-discovery-development-services/kinase-profiling/kinomescan
Reference: 2,5
Key to terms and symbols Click column headers to sort
Target used in screen: MLK2
Ligand Sp. Type Action Value Parameter
tamatinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 8.4 pKd
lestaurtinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 7.8 pKd
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 7.3 pKd
foretinib Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.3 pKd
midostaurin Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 6.1 pKd
NVP-TAE684 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.0 pKd
KW-2449 Small molecule or natural product Hs Inhibitor Inhibition 5.8 pKd
tozasertib Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 5.7 pKd
pazopanib Small molecule or natural product Approved drug Hs Inhibitor Inhibition 5.7 pKd
SB203580 Small molecule or natural product Immunopharmacology Ligand Hs Inhibitor Inhibition <5.5 pKd
Displaying the top 10 most potent ligands  View all ligands in screen »
EMD Millipore KinaseProfilerTM screen/Reaction Biology Kinase HotspotSM screen Click here for help
A screen profiling 158 kinase inhibitors (Calbiochem Protein Kinase Inhibitor Library I and II, catalogue numbers 539744 and 539745) for their inhibitory activity at 1µM and 10µM against 234 human recombinant kinases using the EMD Millipore KinaseProfilerTM service.

A screen profiling the inhibitory activity of 178 commercially available kinase inhibitors at 0.5µM against a panel of 300 recombinant protein kinases using the Reaction Biology Corporation Kinase HotspotSM platform.

http://www.millipore.com/techpublications/tech1/pf3036
http://www.reactionbiology.com/webapps/main/pages/kinase.aspx

Reference: ...1
Key to terms and symbols Click column headers to sort
Target used in screen: nd/MLK2(MAP3K10)
Ligand Sp. Type Action % Activity remaining at 0.5µM % Activity remaining at 1µM % Activity remaining at 10µM
K-252a Small molecule or natural product Hs Inhibitor Inhibition 2.5
SB 218078 Small molecule or natural product Hs Inhibitor Inhibition 2.7
Cdk1/2 inhibitor III Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 3.0
midostaurin Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 3.1
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 3.3
Cdk2 inhibitor IV Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 15.2
bosutinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 22.9
Gö 6976 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 25.8
pazopanib Small molecule or natural product Approved drug Hs Inhibitor Inhibition 28.5
alsterpaullone 2-cyanoethyl Small molecule or natural product Hs Inhibitor Inhibition 30.0
Displaying the top 10 most potent ligands  View all ligands in screen »

References

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1. Anastassiadis T, Deacon SW, Devarajan K, Ma H, Peterson JR. (2011) Comprehensive assay of kinase catalytic activity reveals features of kinase inhibitor selectivity. Nat Biotechnol, 29 (11): 1039-45. [PMID:22037377]

2. Davis MI, Hunt JP, Herrgard S, Ciceri P, Wodicka LM, Pallares G, Hocker M, Treiber DK, Zarrinkar PP. (2011) Comprehensive analysis of kinase inhibitor selectivity. Nat Biotechnol, 29 (11): 1046-51. [PMID:22037378]

3. Goodfellow VS, Loweth CJ, Ravula SB, Wiemann T, Nguyen T, Xu Y, Todd DE, Sheppard D, Pollack S, Polesskaya O et al.. (2013) Discovery, synthesis, and characterization of an orally bioavailable, brain penetrant inhibitor of mixed lineage kinase 3. J Med Chem, 56 (20): 8032-48. [PMID:24044867]

4. Maroney AC, Finn JP, Connors TJ, Durkin JT, Angeles T, Gessner G, Xu Z, Meyer SL, Savage MJ, Greene LA et al.. (2001) Cep-1347 (KT7515), a semisynthetic inhibitor of the mixed lineage kinase family. J Biol Chem, 276 (27): 25302-8. [PMID:11325962]

5. Wodicka LM, Ciceri P, Davis MI, Hunt JP, Floyd M, Salerno S, Hua XH, Ford JM, Armstrong RC, Zarrinkar PP et al.. (2010) Activation state-dependent binding of small molecule kinase inhibitors: structural insights from biochemistry. Chem Biol, 17 (11): 1241-9. [PMID:21095574]

How to cite this page

MLK subfamily: mitogen-activated protein kinase kinase kinase 10. Last modified on 18/02/2015. Accessed on 19/09/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetomalariapharmacology.org/GRAC/ObjectDisplayForward?objectId=2070.