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maternal embryonic leucine zipper kinase

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Target not currently curated in GtoImmuPdb

Target id: 2102

Nomenclature: maternal embryonic leucine zipper kinase

Abbreviated Name: MELK

Family: MELK subfamily

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 651 9p13.2 MELK maternal embryonic leucine zipper kinase
Mouse - 643 4 23.46 cM Melk maternal embryonic leucine zipper kinase
Rat - 362 5q22 Melk maternal embryonic leucine zipper kinase
Previous and Unofficial Names Click here for help
protein kinase Eg3 | Protein kinase PK38
Database Links Click here for help
Alphafold Q14680 (Hs), Q61846 (Mm)
BRENDA 2.7.11.1
ChEMBL Target CHEMBL4578 (Hs)
Ensembl Gene ENSG00000165304 (Hs), ENSMUSG00000035683 (Mm), ENSRNOG00000013598 (Rn)
Entrez Gene 9833 (Hs), 17279 (Mm), 362510 (Rn)
Human Protein Atlas ENSG00000165304 (Hs)
KEGG Enzyme 2.7.11.1
KEGG Gene hsa:9833 (Hs), mmu:17279 (Mm), rno:362510 (Rn)
OMIM 607025 (Hs)
Pharos Q14680 (Hs)
RefSeq Nucleotide NM_001256685 (Hs), NM_010790 (Mm), NM_001108662 (Rn)
RefSeq Protein NP_055606 (Hs), NP_034920 (Mm), NP_001102132 (Rn)
UniProtKB Q14680 (Hs), Q61846 (Mm)
Wikipedia MELK (Hs)
Selected 3D Structures Click here for help
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 Click here for help
EC Number: 2.7.11.1

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
OTSSP167 Small molecule or natural product Hs Inhibition 9.4 pIC50 2
⤷ pIC50 9.4 (IC50 4.1x10-10 M) [2]
MELK-TI Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.6 pIC50 6
⤷ pIC50 7.6 (IC50 2.3x10-8 M) [6]
Description: Measured in a MIllipore kinase screening assay
CC-401 Small molecule or natural product Hs Inhibition 6.5 pIC50 4
⤷ pIC50 6.5 (IC50 3.4x10-7 M) [4]
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: 3,7
Key to terms and symbols Click column headers to sort
Target used in screen: MELK
Ligand Sp. Type Action Value Parameter
lestaurtinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 7.6 pKd
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 7.5 pKd
NVP-TAE684 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 7.0 pKd
PP-242 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.8 pKd
KW-2449 Small molecule or natural product Hs Inhibitor Inhibition 6.7 pKd
tozasertib Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.6 pKd
midostaurin Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 6.6 pKd
foretinib Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.5 pKd
SU-14813 Small molecule or natural product Hs Inhibitor Inhibition 6.5 pKd
sunitinib Small molecule or natural product Approved drug Ligand has a PDB structure 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 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: 1,5
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 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 1.0 1.0 -1.5
K-252a Small molecule or natural product Hs Inhibitor Inhibition 1.2 1.0 -1.0
JAK3 inhibitor VI Small molecule or natural product Hs Inhibitor Inhibition 4.6 4.0 1.0
PKR inhibitor Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 4.7 6.0 1.0
midostaurin Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 4.9 5.0 2.0
JAK inhibitor I Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 5.2 2.0 2.0
dorsomorphin Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.6 5.0 -1.0
SB 218078 Small molecule or natural product Hs Inhibitor Inhibition 7.1 55.0 72.0
dovitinib Small molecule or natural product Hs Inhibitor Inhibition 7.7
sunitinib Small molecule or natural product Approved drug Ligand has a PDB structure 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

References

Show »

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. Edupuganti R, Taliaferro JM, Wang Q, Xie X, Cho EJ, Vidhu F, Ren P, Anslyn EV, Bartholomeusz C, Dalby KN. (2017) Discovery of a potent inhibitor of MELK that inhibits expression of the anti-apoptotic protein Mcl-1 and TNBC cell growth. Bioorg Med Chem, 25 (9): 2609-2616. [PMID:28351607]

5. 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]

6. 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]

7. 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 12/03/2021. Accessed on 18/04/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetoimmunopharmacology.org/GRAC/ObjectDisplayForward?objectId=2102.