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dual specificity tyrosine phosphorylation regulated kinase 1B

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Target id: 2010

Nomenclature: dual specificity tyrosine phosphorylation regulated kinase 1B

Abbreviated Name: DYRK1B

Family: Dyrk1 subfamily

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 629 19q13.2 DYRK1B dual specificity tyrosine phosphorylation regulated kinase 1B
Mouse - 629 7 A3 Dyrk1b dual-specificity tyrosine phosphorylation regulated kinase 1b
Rat - 589 1 q21 Dyrk1b dual specificity tyrosine phosphorylation regulated kinase 1B
Previous and Unofficial Names Click here for help
MIRK | dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 1B | dual specificity tyrosine-(Y)-phosphorylation regulated kinase 1B | dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 1b
Database Links Click here for help
Alphafold Q9Y463 (Hs), Q9Z188 (Mm)
BRENDA 2.7.12.1
ChEMBL Target CHEMBL5543 (Hs)
Ensembl Gene ENSG00000105204 (Hs), ENSMUSG00000002409 (Mm), ENSRNOG00000019254 (Rn)
Entrez Gene 9149 (Hs), 13549 (Mm), 308468 (Rn)
Human Protein Atlas ENSG00000105204 (Hs)
KEGG Enzyme 2.7.12.1
KEGG Gene hsa:9149 (Hs), mmu:13549 (Mm), rno:308468 (Rn)
OMIM 604556 (Hs)
Pharos Q9Y463 (Hs)
RefSeq Nucleotide NM_004714 (Hs), NM_001037957 (Mm), NM_001107496 (Rn)
RefSeq Protein NP_004705 (Hs), NP_001033046 (Mm), NP_001100966 (Rn)
UniProtKB Q9Y463 (Hs), Q9Z188 (Mm)
Wikipedia DYRK1B (Hs)
Enzyme Reaction Click here for help
EC Number: 2.7.12.1

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
compound 68 [PMID: 24900699] Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 9.6 pIC50 9
⤷ pIC50 9.6 (IC50 2.4x10-10 M) [9]
compound 72 [WO2013026806] Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 9.6 pIC50 7
⤷ pIC50 9.6 (IC50 2.8x10-10 M) [7]
compound 17 [PMID: 23642479] Small molecule or natural product Click here for species-specific activity table Hs Inhibition 8.1 pIC50 3
⤷ pIC50 8.1 (IC50 7x10-9 M) [3]
AZ191 Small molecule or natural product Primary target of this compound Ligand has a PDB structure Hs Inhibition 7.8 pIC50 6
⤷ pIC50 7.8 (IC50 1.7x10-8 M) [6]
compound 3b [PMID: 23454515] Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.1 pIC50 2
⤷ pIC50 7.1 (IC50 7.2x10-8 M) [2]
voruciclib Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.0 pIC50 8
⤷ pIC50 7.0 (IC50 9.4x10-8 M) [8]
harmine Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 6.8 pIC50 5
⤷ pIC50 6.8 (IC50 1.66x10-7 M) [5]
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: 4,10
Key to terms and symbols Click column headers to sort
Target used in screen: DYRK1B
Ligand Sp. Type Action Value Parameter
A-674563 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 8.4 pKd
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 7.6 pKd
lestaurtinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 7.5 pKd
alvocidib Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 7.1 pKd
BMS-387032 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.7 pKd
R547 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.6 pKd
AT-7519 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.5 pKd
midostaurin Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 6.5 pKd
TG-100-115 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.1 pKd
KW-2449 Small molecule or natural product Hs Inhibitor Inhibition 6.0 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/DYRK1B
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 0.8
SB 218078 Small molecule or natural product Hs Inhibitor Inhibition 3.1
K-252a Small molecule or natural product Hs Inhibitor Inhibition 3.9
JAK3 inhibitor VI Small molecule or natural product Hs Inhibitor Inhibition 5.0
PKR inhibitor Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 11.3
Cdk1/2 inhibitor III Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 14.1
Gö 6976 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 25.6
dorsomorphin Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 26.2
PI 3-Kg inhibitor Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 31.3
Cdc2-like kinase inhibitor Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 32.9
Displaying the top 10 most potent ligands  View all ligands in screen »
Clinically-Relevant Mutations and Pathophysiology Click here for help
Disease:  Abdominal obesity-metabolic syndrome 3; AOMS3
OMIM: 615812

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. Burgy G, Tahtouh T, Durieu E, Foll-Josselin B, Limanton E, Meijer L, Carreaux F, Bazureau JP. (2013) Chemical synthesis and biological validation of immobilized protein kinase inhibitory Leucettines. Eur J Med Chem, 62: 728-37. [PMID:23454515]

3. Coombs TC, Tanega C, Shen M, Wang JL, Auld DS, Gerritz SW, Schoenen FJ, Thomas CJ, Aubé J. (2013) Small-molecule pyrimidine inhibitors of the cdc2-like (Clk) and dual specificity tyrosine phosphorylation-regulated (Dyrk) kinases: development of chemical probe ML315. Bioorg Med Chem Lett, 23 (12): 3654-61. [PMID:23642479]

4. 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]

5. Göckler N, Jofre G, Papadopoulos C, Soppa U, Tejedor FJ, Becker W. (2009) Harmine specifically inhibits protein kinase DYRK1A and interferes with neurite formation. FEBS J, 276 (21): 6324-37. [PMID:19796173]

6. Kettle JG, Ballard P, Bardelle C, Cockerill M, Colclough N, Critchlow SE, Debreczeni J, Fairley G, Fillery S, Graham MA et al.. (2015) Discovery and optimization of a novel series of Dyrk1B kinase inhibitors to explore a MEK resistance hypothesis. J Med Chem, 58 (6): 2834-44. [PMID:25738750]

7. Leblond B, Casagrande A-S, Desire L, Foucourt A, Besson T. (2013) Dyrk1 inhibitors and uses thereof. Patent number: WO2013026806. Assignee: Exonhit Sa. Priority date: 19/08/2011. Publication date: 28/02/2013.

8. Paiva C, Godbersen JC, Soderquist RS, Rowland T, Kilmarx S, Spurgeon SE, Brown JR, Srinivasa SP, Danilov AV. (2015) Cyclin-Dependent Kinase Inhibitor P1446A Induces Apoptosis in a JNK/p38 MAPK-Dependent Manner in Chronic Lymphocytic Leukemia B-Cells. PLoS ONE, 10 (11): e0143685. [PMID:26606677]

9. Rosse G. (2013) Tricyclic Pyrimidines As Inhibitors of DYRK1A/DYRK1B As Potential Treatment for Down's Syndrome or Alzheimer's Disease. ACS Med Chem Lett, 4 (6): 502-3. [PMID:24900699]

10. 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

Dyrk1 subfamily: dual specificity tyrosine phosphorylation regulated kinase 1B. Last modified on 25/04/2018. Accessed on 16/04/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetomalariapharmacology.org/GRAC/ObjectDisplayForward?objectId=2010.