maternal embryonic leucine zipper kinase | MELK subfamily | IUPHAR/BPS Guide to PHARMACOLOGY

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maternal embryonic leucine zipper kinase

Target not currently curated in GtoImmuPdb

Target id: 2102

Nomenclature: maternal embryonic leucine zipper kinase

Abbreviated Name: MELK

Family: MELK subfamily

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 651 9p13.1 MELK maternal embryonic leucine zipper kinase
Mouse - 643 4 B1 Melk maternal embryonic leucine zipper kinase
Rat - 362 5q22 Melk maternal embryonic leucine zipper kinase
Previous and Unofficial Names
protein kinase Eg3 | Protein kinase PK38
Database Links
BRENDA
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
KEGG Gene
OMIM
Pharos
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Selected 3D Structures
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of Maternal Embryonic Leucine zipper Kinase (MELK) in complex with AMP-PNP
PDB Id:  4BL1
Ligand:  AMP-PNP
Resolution:  2.6Å
Species:  Human
References: 
Enzyme Reaction
EC Number: 2.7.11.1

Download all structure-activity data for this target as a CSV file

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
OTSSP167 Hs Inhibition 9.4 pIC50 2
pIC50 9.4 (IC50 4.1x10-10 M) [2]
MELK-TI Hs Inhibition 7.6 pIC50 5
pIC50 7.6 (IC50 2.3x10-8 M) [5]
Description: Measured in a MIllipore kinase screening assay
DiscoveRx KINOMEscan® screen
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: 3,6

Key to terms and symbols Click column headers to sort
Target used in screen: MELK
Ligand Sp. Type Action Value Parameter
lestaurtinib Hs Inhibitor Inhibition 7.6 pKd
staurosporine Hs Inhibitor Inhibition 7.5 pKd
NVP-TAE684 Hs Inhibitor Inhibition 7.0 pKd
PP-242 Hs Inhibitor Inhibition 6.8 pKd
KW-2449 Hs Inhibitor Inhibition 6.7 pKd
tozasertib Hs Inhibitor Inhibition 6.6 pKd
midostaurin Hs Inhibitor Inhibition 6.6 pKd
foretinib Hs Inhibitor Inhibition 6.5 pKd
SU-14813 Hs Inhibitor Inhibition 6.5 pKd
sunitinib Hs Inhibitor Inhibition 6.5 pKd
Displaying the top 10 most potent ligands  View all ligands in screen »
EMD Millipore KinaseProfilerTM screen/Reaction Biology Kinase HotspotSM screen
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: 1,4

Key to terms and symbols Click column headers to sort
Target used in screen: MELK/MELK
Ligand Sp. Type Action % Activity remaining at 0.5µM % Activity remaining at 1µM % Activity remaining at 10µM
staurosporine Hs Inhibitor Inhibition 1.0 1.0 -1.5
K-252a Hs Inhibitor Inhibition 1.2 1.0 -1.0
JAK3 inhibitor VI Hs Inhibitor Inhibition 4.6 4.0 1.0
PKR inhibitor Hs Inhibitor Inhibition 4.7 6.0 1.0
midostaurin Hs Inhibitor Inhibition 4.9 5.0 2.0
JAK inhibitor I Hs Inhibitor Inhibition 5.2 2.0 2.0
dorsomorphin Hs Inhibitor Inhibition 6.6 5.0 -1.0
SB 218078 Hs Inhibitor Inhibition 7.1 55.0 72.0
dovitinib Hs Inhibitor Inhibition 7.7
sunitinib Hs Inhibitor Inhibition 10.4
Displaying the top 10 most potent ligands  View all ligands in screen »
Immuno Process Associations
Immuno Process:  Immune system development
GO Annotations:  Associated to 1 GO processes
GO:0030097 hemopoiesis ISS

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. Chung S, Suzuki H, Miyamoto T, Takamatsu N, Tatsuguchi A, Ueda K, Kijima K, Nakamura Y, Matsuo Y. (2012) Development of an orally-administrative MELK-targeting inhibitor that suppresses the growth of various types of human cancer. Oncotarget, 3 (12): 1629-40. [PMID:23283305]

3. 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]

4. Gao Y, Davies SP, Augustin M, Woodward A, Patel UA, Kovelman R, Harvey KJ. (2013) A broad activity screen in support of a chemogenomic map for kinase signalling research and drug discovery. Biochem. J., 451 (2): 313-28. [PMID:23398362]

5. Johnson CN, Berdini V, Beke L, Bonnet P, Brehmer D, Coyle JE, Day PJ, Frederickson M, Freyne EJ, Gilissen RA et al.. (2014) Fragment-based discovery of type I inhibitors of maternal embryonic leucine zipper kinase. ACS Med Chem Lett, 6 (1): 25-30. [PMID:25589925]

6. 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

MELK subfamily: maternal embryonic leucine zipper kinase. Last modified on 07/11/2016. Accessed on 19/09/2020. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2102.