ribosomal protein S6 kinase A1 | RSK subfamily | IUPHAR/BPS Guide to PHARMACOLOGY

Top ▲

ribosomal protein S6 kinase A1

Target not currently curated in GtoImmuPdb

Target id: 1527

Nomenclature: ribosomal protein S6 kinase A1

Abbreviated Name: p90RSK

Family: RSK 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 - 744 1p RPS6KA1 ribosomal protein S6 kinase A1
Mouse - 735 4 D3 Rps6ka1 ribosomal protein S6 kinase polypeptide 1
Rat - 735 5q36 Rps6ka1 ribosomal protein S6 kinase A1
Previous and Unofficial Names
90 kDa ribosomal protein S6 kinase 1 | HU-1 | MAPKAPK1A | MAPKAP kinase 1a | MAP kinase-activated protein kinase 1a | p90RSK1 | p90S6K | ribosomal protein S6 kinase, 90kDa, polypeptide 1 | ribosomal protein S6 kinase, 90kD, polypeptide 1 | ribosomal protein S6 kinase alpha-1 | ribosomal protein S6 kinase, polypeptide A1
Database Links
BRENDA
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
KEGG Gene
OMIM
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Selected 3D Structures
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of the N-terminal kinase domain of human RSK-1 bound to AMP-PCP
PDB Id:  2Z7Q
Resolution:  2.0Å
Species:  Human
References:  6
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of the human ribosomal protein S6 kinase
PDB Id:  2WNT
Resolution:  2.4Å
Species:  Human
References: 
Enzyme Reaction
EC Number: 2.7.11.1

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 Value Parameter Reference
prexasertib Hs Inhibition 8.1 pIC50 7
pIC50 8.1 (IC50 9x10-9 M) [7]
Description: Enzyme assay
BI-D1870 Hs Inhibition 7.5 pIC50 11
pIC50 7.5 (IC50 3.1x10-8 M) [11]
compound E22 [PMID: 31298542] Hs Inhibition 6.9 pIC50 3
pIC50 6.9 (IC50 1.31x10-7 M) [3]
dorsomorphin Hs Inhibition 6.7 pIC50 9
pIC50 6.7 (IC50 2.1x10-7 M) [9]
Description: Assayed using AMPK heterotrimeric complex containing α2, β1, γ1 subunits
compound 33 [PMID: 19364658] Hs Inhibition 6.5 pIC50 8
pIC50 6.5 (IC50 2.9x10-7 M) [8]
GSK429286A Hs Inhibition 6.1 pIC50 5
pIC50 6.1 (IC50 7.8x10-7 M) [5]
GSK-1838705A Hs Inhibition 5.8 pIC50 10
pIC50 5.8 (IC50 1.6x10-6 M) [10]
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: 2,12

Key to terms and symbols Click column headers to sort
Target used in screen: RSK1(Kin.Dom.1-N-terminal)
Ligand Sp. Type Action Value Parameter
lestaurtinib Hs Inhibitor Inhibition 7.6 pKd
staurosporine Hs Inhibitor Inhibition 7.4 pKd
sunitinib Hs Inhibitor Inhibition 6.8 pKd
NVP-TAE684 Hs Inhibitor Inhibition 6.8 pKd
SU-14813 Hs Inhibitor Inhibition 6.7 pKd
ruboxistaurin Hs Inhibitor Inhibition 6.4 pKd
GSK-1838705A Hs Inhibitor Inhibition 6.4 pKd
dovitinib Hs Inhibitor Inhibition 6.3 pKd
tamatinib Hs Inhibitor Inhibition 6.3 pKd
midostaurin Hs Inhibitor Inhibition 6.2 pKd
Target used in screen: RSK1(Kin.Dom.2-C-terminal)
Ligand Sp. Type Action Value Parameter
ruxolitinib Hs Inhibitor Inhibition 6.9 pKd
TG-100-115 Hs Inhibitor Inhibition 6.7 pKd
SB203580 Hs Inhibitor Inhibition 6.5 pKd
vandetanib Hs Inhibitor Inhibition 6.4 pKd
fedratinib Hs Inhibitor Inhibition 6.4 pKd
NVP-TAE684 Hs Inhibitor Inhibition 6.2 pKd
alvocidib Hs Inhibitor Inhibition 6.1 pKd
staurosporine Hs Inhibitor Inhibition 5.9 pKd
tofacitinib Hs Inhibitor Inhibition 5.8 pKd
lestaurtinib Hs Inhibitor Inhibition 5.6 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: 1,4

Key to terms and symbols Click column headers to sort
Target used in screen: Rsk1/RSK1
Ligand Sp. Type Action % Activity remaining at 0.5µM % Activity remaining at 1µM % Activity remaining at 10µM
K-252a Hs Inhibitor Inhibition -6.0 1.0 2.0
midostaurin Hs Inhibitor Inhibition 0.4 0.0 1.0
JAK3 inhibitor VI Hs Inhibitor Inhibition 0.9 10.0 2.0
SB 218078 Hs Inhibitor Inhibition 1.6 13.0 7.0
staurosporine Hs Inhibitor Inhibition 3.5 3.5 1.0
GF109203X Hs Inhibitor Inhibition 4.7 15.0 2.0
Cdk1/2 inhibitor III Hs Inhibitor Inhibition 5.3 4.0 3.0
Ro-32-0432 Hs Inhibitor Inhibition 5.9
PKCbeta inhibitor Hs Inhibitor Inhibition 7.5 8.0 1.0
indirubin derivative E804 Hs Inhibitor Inhibition 8.9 18.0 12.0
Displaying the top 10 most potent ligands  View all ligands in screen »

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. 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. Dong X, Zhan W, Zhao M, Che J, Dai X, Wu Y, Xu L, Zhou Y, Zhao Y, Tian T et al.. (2019) Discovery of 3,4,6-Trisubstituted Piperidine Derivatives as Orally Active, Low hERG Blocking Akt Inhibitors via Conformational Restriction and Structure-Based Design. J. Med. Chem., 62 (15): 7264-7288. [PMID:31298542]

4. Gao Y, Davies SP, Augustin M, Woodward A, Patel UA, Kovelman R, Harvey KJ. (2013) A broad activity screen in support of a chemogenomic map for kinase signalling research and drug discovery. Biochem. J., 451 (2): 313-28. [PMID:23398362]

5. Goodman KB, Cui H, Dowdell SE, Gaitanopoulos DE, Ivy RL, Sehon CA, Stavenger RA, Wang GZ, Viet AQ, Xu W et al.. (2007) Development of dihydropyridone indazole amides as selective Rho-kinase inhibitors. J. Med. Chem., 50 (1): 6-9. [PMID:17201405]

6. Ikuta M, Kornienko M, Byrne N, Reid JC, Mizuarai S, Kotani H, Munshi SK. (2007) Crystal structures of the N-terminal kinase domain of human RSK1 bound to three different ligands: Implications for the design of RSK1 specific inhibitors. Protein Sci., 16 (12): 2626-35. [PMID:17965187]

7. King C, Diaz HB, McNeely S, Barnard D, Dempsey J, Blosser W, Beckmann R, Barda D, Marshall MS. (2015) LY2606368 Causes Replication Catastrophe and Antitumor Effects through CHK1-Dependent Mechanisms. Mol. Cancer Ther., 14 (9): 2004-13. [PMID:26141948]

8. Lovering F, Kirincich S, Wang W, Combs K, Resnick L, Sabalski JE, Butera J, Liu J, Parris K, Telliez JB. (2009) Identification and SAR of squarate inhibitors of mitogen activated protein kinase-activated protein kinase 2 (MK-2). Bioorg. Med. Chem., 17 (9): 3342-51. [PMID:19364658]

9. Machrouhi F, Ouhamou N, Laderoute K, Calaoagan J, Bukhtiyarova M, Ehrlich PJ, Klon AE. (2010) The rational design of a novel potent analogue of the 5'-AMP-activated protein kinase inhibitor compound C with improved selectivity and cellular activity. Bioorg. Med. Chem. Lett., 20 (22): 6394-9. [PMID:20932747]

10. Sabbatini P, Korenchuk S, Rowand JL, Groy A, Liu Q, Leperi D, Atkins C, Dumble M, Yang J, Anderson K et al.. (2009) GSK1838705A inhibits the insulin-like growth factor-1 receptor and anaplastic lymphoma kinase and shows antitumor activity in experimental models of human cancers. Mol. Cancer Ther., 8 (10): 2811-20. [PMID:19825801]

11. Sapkota GP, Cummings L, Newell FS, Armstrong C, Bain J, Frodin M, Grauert M, Hoffmann M, Schnapp G, Steegmaier M et al.. (2007) BI-D1870 is a specific inhibitor of the p90 RSK (ribosomal S6 kinase) isoforms in vitro and in vivo. Biochem. J., 401 (1): 29-38. [PMID:17040210]

12. 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

RSK subfamily: ribosomal protein S6 kinase A1. Last modified on 25/07/2019. Accessed on 08/12/2019. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1527.