dual specificity tyrosine phosphorylation regulated kinase 1B | Dyrk1 subfamily | IUPHAR/BPS Guide to PHARMACOLOGY

dual specificity tyrosine phosphorylation regulated kinase 1B

Target id: 2010

Nomenclature: dual specificity tyrosine phosphorylation regulated kinase 1B

Abbreviated Name: DYRK1B

Family: Dyrk1 subfamily

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

   GtoImmuPdb view: OFF :     Currently no data for dual specificity tyrosine phosphorylation regulated kinase 1B in GtoImmuPdb

Gene and Protein Information
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-(Y)-phosphorylation regulated kinase 1b
Rat - 589 1 q21 Dyrk1b dual specificity tyrosine phosphorylation regulated kinase 1B
Previous and Unofficial Names
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
BRENDA
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
KEGG Gene
OMIM
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Enzyme Reaction
EC Number: 2.7.12.1

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 Affinity Units Reference
compound 68 [PMID: 24900699] Hs Inhibition 9.6 pIC50 9
pIC50 9.6 (IC50 2.4x10-10 M) [9]
compound 72 [WO2013026806] Hs Inhibition 9.6 pIC50 7
pIC50 9.6 (IC50 2.8x10-10 M) [7]
compound 17 [PMID: 23642479] Hs Inhibition 8.1 pIC50 3
pIC50 8.1 (IC50 7x10-9 M) [3]
AZ191 Hs Inhibition 7.8 pIC50 6
pIC50 7.8 (IC50 1.7x10-8 M) [6]
compound 3b [PMID: 23454515] Hs Inhibition 7.1 pIC50 2
pIC50 7.1 (IC50 7.2x10-8 M) [2]
voruciclib Hs Inhibition 7.0 pIC50 8
pIC50 7.0 (IC50 9.4x10-8 M) [8]
harmine Hs Inhibition 6.8 pIC50 5
pIC50 6.8 (IC50 1.66x10-7 M) [5]
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: 4,10

Key to terms and symbols Click column headers to sort
Target used in screen: DYRK1B
Ligand Sp. Type Action Affinity Units
A-674563 Hs Inhibitor Inhibition 8.4 pKd
staurosporine Hs Inhibitor Inhibition 7.6 pKd
lestaurtinib Hs Inhibitor Inhibition 7.5 pKd
alvocidib Hs Inhibitor Inhibition 7.1 pKd
BMS-387032 Hs Inhibitor Inhibition 6.7 pKd
R547 Hs Inhibitor Inhibition 6.6 pKd
AT-7519 Hs Inhibitor Inhibition 6.5 pKd
midostaurin Hs Inhibitor Inhibition 6.5 pKd
TG-100-115 Hs Inhibitor Inhibition 6.1 pKd
KW-2449 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
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 Hs Inhibitor Inhibition 0.8
SB 218078 Hs Inhibitor Inhibition 3.1
K-252a Hs Inhibitor Inhibition 3.9
JAK3 inhibitor VI Hs Inhibitor Inhibition 5.0
PKR inhibitor Hs Inhibitor Inhibition 11.3
Cdk1/2 inhibitor III Hs Inhibitor Inhibition 14.1
Gö 6976 Hs Inhibitor Inhibition 25.6
dorsomorphin Hs Inhibitor Inhibition 26.2
PI 3-Kg inhibitor Hs Inhibitor Inhibition 31.3
Cdc2-like kinase inhibitor Hs Inhibitor Inhibition 32.9
Displaying the top 10 most potent ligands  View all ligands in screen »
Clinically-Relevant Mutations and Pathophysiology
Disease:  Abdominal obesity-metabolic syndrome 3; AOMS3
OMIM: 615812

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. 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 17/11/2018. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2010.