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ZAK sterile alpha motif and leucine zipper containing kinase AZK

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Target id: 2289

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

Abbreviated Name: ZAK

Family: MLK subfamily

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 800 2q31.1 MAP3K20 mitogen-activated protein kinase kinase kinase 20
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 Click here for help
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 Click here for help
Alphafold Q9NYL2 (Hs), Q9ESL4 (Mm)
BRENDA 2.7.11.25
ChEMBL Target CHEMBL3886 (Hs), CHEMBL4523452 (Mm)
Ensembl Gene ENSG00000091436 (Hs), ENSMUSG00000004085 (Mm), ENSRNOG00000001515 (Rn)
Entrez Gene 51776 (Hs), 65964 (Mm), 311743 (Rn)
Human Protein Atlas ENSG00000091436 (Hs)
KEGG Enzyme 2.7.11.25
KEGG Gene hsa:51776 (Hs), mmu:65964 (Mm), rno:311743 (Rn)
OMIM 609479 (Hs)
Pharos Q9NYL2 (Hs)
RefSeq Nucleotide NM_016653 (Hs), NM_023057 (Mm), XM_002729174 (Rn)
RefSeq Protein NP_057737 (Hs), NP_075544 (Mm), XP_001059755 (Rn)
UniProtKB Q9NYL2 (Hs), Q9ESL4 (Mm)
Wikipedia MAP3K20 (Hs)
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
ZAK inhibitor 6p Small molecule or natural product Primary target of this compound Click here for species-specific activity table 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 Small molecule or natural product Click here for species-specific activity table 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.
KC-130 Small molecule or natural product Hs Inhibition 7.9 pIC50 6
⤷ pIC50 7.9 (IC50 1.15x10-8 M) [6]
compound 15b [PMID: 16539403] Small molecule or natural product Click here for species-specific activity table Hs Inhibition 6.2 pIC50 3
⤷ pIC50 6.2 (IC50 7.08x10-7 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: 2,4
Key to terms and symbols Click column headers to sort
Target used in screen: ZAK
Ligand Sp. Type Action Value Parameter
AST-487 Small molecule or natural product Hs Inhibitor Inhibition 8.6 pKd
sorafenib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 8.2 pKd
motesanib Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 8.1 pKd
nilotinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 8.0 pKd
PLX-4720 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 7.4 pKd
dasatinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 7.3 pKd
foretinib Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 7.3 pKd
CHIR-265 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 7.2 pKd
bosutinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 7.1 pKd
PD-173955 Small molecule or natural product 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
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 Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 8.6
dorsomorphin Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 11.7
TWS119 Small molecule or natural product Hs Inhibitor Inhibition 13.9
sorafenib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 16.7
nilotinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 17.8
Flt-3 inhibitor III Small molecule or natural product Hs Inhibitor Inhibition 25.9
Flt-3 inhibitor II Small molecule or natural product Hs Inhibitor Inhibition 34.3
PDGF receptor tyrosine kinase inhibitor IV Small molecule or natural product Hs Inhibitor Inhibition 44.7
Cdk1/2 inhibitor III Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 49.1
PKR inhibitor Small molecule or natural product Ligand has a PDB structure 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 ZC, Yun CH, Huang CY, Ding K et al.. (2020) Design, Synthesis, and Structure-Activity Relationships of 1,2,3-Triazole Benzenesulfonamides as New Selective Leucine-Zipper and Sterile-α Motif Kinase (ZAK) Inhibitors. J Med Chem, 63 (5): 2114-2130. [PMID:31244114]

6. Zhou Y, Yu H, Vind AC, Kong L, Liu Y, Song X, Tu Z, Yun C, Smaill JB, Zhang QW et al.. (2023) Rational Design of Covalent Kinase Inhibitors by an Integrated Computational Workflow (Kin-Cov). J Med Chem, 66 (11): 7405-7420. [PMID:37220641]

How to cite this page

MLK subfamily: ZAK sterile alpha motif and leucine zipper containing kinase AZK. Last modified on 02/08/2023. Accessed on 19/04/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetomalariapharmacology.org/GRAC/ObjectDisplayForward?objectId=2289.