ZAK sterile alpha motif and leucine zipper containing kinase AZK | MLK subfamily | IUPHAR/BPS Guide to PHARMACOLOGY

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ZAK sterile alpha motif and leucine zipper containing kinase AZK

Target not currently curated in GtoImmuPdb

Target id: 2289

Nomenclature: ZAK sterile alpha motif and leucine zipper containing kinase AZK

Abbreviated Name: ZAK

Family: MLK subfamily

Annotation status:  image of an orange circle Annotated and awaiting review. Please contact us if you can help with reviewing.  » Email us

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 800 2q24.2 ZAK ZAK sterile alpha motif and leucine zipper containing kinase AZK
Mouse - 802 2 C3 Map3k20 mitogen-activated protein kinase kinase kinase 20
Rat - 802 3q22 Map3k20 mitogen-activated protein kinase kinase kinase 20
Previous and Unofficial Names
Zak | HCCS-4 | mitogen-activated protein kinase kinase kinase MLT | mixed lineage kinase 7 | MLK7 | MLK-like mitogen-activated protein triple kinase | human cervical cancer suppressor gene 4 protein | MLK-related kinase | sterile alpha motif and leucine zipper containing kinase AZK
Database Links
BRENDA
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
KEGG Gene
OMIM
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Enzyme Reaction
EC Number: 2.7.11.25

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
ZAK inhibitor 6p Hs Inhibition 8.1 pKd 5
pKd 8.1 (Kd 8x10-9 M) [5]
Description: Binding affinity determined using an active site-dependent competition binding assay.
ZAK inhibitor 6p Hs Inhibition 8.4 pIC50 5
pIC50 8.4 (IC50 4x10-9 M) [5]
Description: Inhibition of enzymatic activity determined in a ADP-GloTM assay.
compound 15b [PMID: 16539403] Hs Inhibition 6.2 pIC50 3
pIC50 6.2 (IC50 7.08x10-7 M) [3]
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: 2,4

Key to terms and symbols Click column headers to sort
Target used in screen: ZAK
Ligand Sp. Type Action Value Parameter
AST-487 Hs Inhibitor Inhibition 8.6 pKd
sorafenib Hs Inhibitor Inhibition 8.2 pKd
motesanib Hs Inhibitor Inhibition 8.1 pKd
nilotinib Hs Inhibitor Inhibition 8.0 pKd
PLX-4720 Hs Inhibitor Inhibition 7.4 pKd
dasatinib Hs Inhibitor Inhibition 7.3 pKd
foretinib Hs Inhibitor Inhibition 7.3 pKd
CHIR-265 Hs Inhibitor Inhibition 7.2 pKd
bosutinib Hs Inhibitor Inhibition 7.1 pKd
PD-173955 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

Key to terms and symbols Click column headers to sort
Target used in screen: nd/ZAK(MLTK)
Ligand Sp. Type Action % Activity remaining at 0.5µM % Activity remaining at 1µM % Activity remaining at 10µM
dasatinib Hs Inhibitor Inhibition 8.6
dorsomorphin Hs Inhibitor Inhibition 11.7
TWS119 Hs Inhibitor Inhibition 13.9
sorafenib Hs Inhibitor Inhibition 16.7
nilotinib Hs Inhibitor Inhibition 17.8
Flt-3 inhibitor III Hs Inhibitor Inhibition 25.9
Flt-3 inhibitor II Hs Inhibitor Inhibition 34.3
PDGF receptor tyrosine kinase inhibitor IV Hs Inhibitor Inhibition 44.7
Cdk1/2 inhibitor III Hs Inhibitor Inhibition 49.1
PKR inhibitor Hs Inhibitor Inhibition 52.8
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. Li HY, Wang Y, Heap CR, King CH, Mundla SR, Voss M, Clawson DK, Yan L, Campbell RM, Anderson BD et al.. (2006) Dihydropyrrolopyrazole transforming growth factor-beta type I receptor kinase domain inhibitors: a novel benzimidazole series with selectivity versus transforming growth factor-beta type II receptor kinase and mixed lineage kinase-7. J. Med. Chem., 49 (6): 2138-42. [PMID:16539403]

4. 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]

5. Yang J, Shibu MA, Kong L, Luo J, BadrealamKhan F, Huang Y, Tu Z-C, Yun C-H, Huang C-Y, Ding K, Lu X. (2019) Design, Synthesis and Structure-Activity Relationships of 1,2,3-Triazole Benzenesulfonamides as new Selective Leucine- Zipper and Sterile-α Motif Kinase (ZAK) Inhibitors. Journal of Medicinal Chemistry, Just Accepted Manuscript. DOI: 10.1021/acs.jmedchem.9b00664

How to cite this page

MLK subfamily: ZAK sterile alpha motif and leucine zipper containing kinase AZK. Last modified on 06/06/2019. Accessed on 20/06/2019. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2289.