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microtubule affinity regulating kinase 3

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Target not currently curated in GtoImmuPdb

Target id: 2099

Nomenclature: microtubule affinity regulating kinase 3

Abbreviated Name: MARK3

Family: MARK subfamily

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 753 14q32.32-q32.33 MARK3 microtubule affinity regulating kinase 3
Mouse - 753 12 F1 Mark3 MAP/microtubule affinity regulating kinase 3
Rat - 797 6q32 Mark3 microtubule affinity regulating kinase 3
Previous and Unofficial Names Click here for help
CTAK1 | Cdc25C-associated protein kinase 1 | ELKL motif kinase 2 | EMK2 | Par-1a | Protein kinase STK10 | MAP/microtubule affinity-regulating kinase 3
Database Links Click here for help
Alphafold P27448 (Hs), Q03141 (Mm), Q8VHF0 (Rn)
BRENDA 2.7.11.1
ChEMBL Target CHEMBL5600 (Hs)
Ensembl Gene ENSG00000075413 (Hs), ENSMUSG00000007411 (Mm), ENSRNOG00000010330 (Rn)
Entrez Gene 4140 (Hs), 17169 (Mm), 170577 (Rn)
Human Protein Atlas ENSG00000075413 (Hs)
KEGG Enzyme 2.7.11.1
KEGG Gene hsa:4140 (Hs), mmu:17169 (Mm), rno:170577 (Rn)
OMIM 602678 (Hs)
Pharos P27448 (Hs)
RefSeq Nucleotide NM_001128918 (Hs), NM_021516 (Mm), NM_130749 (Rn)
RefSeq Protein NP_001122390 (Hs), NP_067491 (Mm), NP_570105 (Rn)
UniProtKB P27448 (Hs), Q03141 (Mm), Q8VHF0 (Rn)
Wikipedia MARK3 (Hs)
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  Kinase and Ubiquitin-associated domains of MARK3/Par-1
PDB Id:  2QNJ
Resolution:  2.7Å
Species:  Human
References:  6
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
PCC0208017 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 8.7 pIC50 4
⤷ pIC50 8.7 (IC50 1.8x10-9 M) [4]
PCC0105003 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 8.6 pIC50 7
⤷ pIC50 8.6 (IC50 2.67x10-9 M) [7]
compound 17d [PMID: 23099093] Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 7.9 pIC50 5
⤷ pIC50 7.9 (IC50 1.2x10-8 M) [5]
compound 14 [PMID: 34333981] Small molecule or natural product Click here for species-specific activity table Hs Inhibition 5.4 pIC50 3
⤷ pIC50 5.4 (IC50 4.015x10-6 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: 2,8
Key to terms and symbols Click column headers to sort
Target used in screen: MARK3
Ligand Sp. Type Action Value Parameter
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 8.5 pKd
NVP-TAE684 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 7.9 pKd
midostaurin Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 7.7 pKd
lestaurtinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 7.3 pKd
fedratinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 6.5 pKd
sunitinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 6.4 pKd
PD-173955 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.1 pKd
SU-14813 Small molecule or natural product Hs Inhibitor Inhibition 6.0 pKd
KW-2449 Small molecule or natural product Hs Inhibitor Inhibition 5.9 pKd
tamatinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 5.7 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/MARK3
Ligand Sp. Type Action % Activity remaining at 0.5µM % Activity remaining at 1µM % Activity remaining at 10µM
Cdk1/2 inhibitor III Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 0.3
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 0.7
K-252a Small molecule or natural product Hs Inhibitor Inhibition 1.8
JAK3 inhibitor VI Small molecule or natural product Hs Inhibitor Inhibition 3.9
midostaurin Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 4.8
SU11652 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 7.9
SB 218078 Small molecule or natural product Hs Inhibitor Inhibition 8.5
Gö 6976 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 13.9
PKR inhibitor Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 21.3
isogranulatimide Small molecule or natural product Hs Inhibitor Inhibition 29.8
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. Drewry DH, Annor-Gyamfi JK, Wells CI, Pickett JE, Dederer V, Preuss F, Mathea S, Axtman AD. (2022) Identification of Pyrimidine-Based Lead Compounds for Understudied Kinases Implicated in Driving Neurodegeneration. J Med Chem, 65 (2): 1313-1328. [PMID:34333981]

4. Li F, Liu Z, Sun H, Li C, Wang W, Ye L, Yan C, Tian J, Wang H. (2020) PCC0208017, a novel small-molecule inhibitor of MARK3/MARK4, suppresses glioma progression in vitro and in vivo. Acta Pharm Sin B, 10 (2): 289-300. [PMID:32082974]

5. McIver EG, Bryans J, Birchall K, Chugh J, Drake T, Lewis SJ, Osborne J, Smiljanic-Hurley E, Tsang W, Kamal A et al.. (2012) Synthesis and structure-activity relationships of a novel series of pyrimidines as potent inhibitors of TBK1/IKKε kinases. Bioorg Med Chem Lett, 22 (23): 7169-73. [PMID:23099093]

6. Murphy JM, Korzhnev DM, Ceccarelli DF, Briant DJ, Zarrine-Afsar A, Sicheri F, Kay LE, Pawson T. (2007) Conformational instability of the MARK3 UBA domain compromises ubiquitin recognition and promotes interaction with the adjacent kinase domain. Proc Natl Acad Sci USA, 104 (36): 14336-41. [PMID:17726107]

7. Shi YQ, Sun ZH, Wang ZZ, Su CY, Zhang W, Yu LY, Xu Y, Gao YL, Wang HB, Tian JW et al.. (2023) A novel role for microtubule affinity-regulating kinases in neuropathic pain. Br J Pharmacol, [Epub ahead of print]. [PMID:38112022]

8. 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

MARK subfamily: microtubule affinity regulating kinase 3. Last modified on 12/03/2024. Accessed on 16/04/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2099.