ribosomal protein S6 kinase A3 | RSK subfamily | IUPHAR/BPS Guide to PHARMACOLOGY

Top ▲

ribosomal protein S6 kinase A3

Target not currently curated in GtoImmuPdb

Target id: 1528

Nomenclature: ribosomal protein S6 kinase A3

Abbreviated Name: RSK2

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 - 740 Xp22.2-p22.1 RPS6KA3 ribosomal protein S6 kinase A3
Mouse - 740 X Rps6ka3 ribosomal protein S6 kinase polypeptide 3
Rat - 740 Xq21 Rps6ka3 ribosomal protein S6 kinase A3
Previous and Unofficial Names
ISPK1  | MAPKAPK1B | RSKα3 | Coffin-Lowry syndrome | mental retardation, X-linked 19 | ribosomal protein S6 kinase, 90kD, polypeptide 3 | ribosomal protein S6 kinase alpha-3 | CLS | HU-3 | MRX19 | ribosomal protein S6 kinase, 90kDa, polypeptide 3
Database Links
BRENDA
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
KEGG Gene
OMIM
Orphanet
RefSeq Nucleotide
RefSeq Protein
SynPHARM
UniProtKB
Wikipedia
Selected 3D Structures
Image of receptor 3D structure from RCSB PDB
Description:  Rsk2 C-terminal Kinase Domain with inhibitor (E)-methyl 3-(4-amino-7-(3-hydroxypropyl)-5-p-tolyl-7H-pyrrolo[2,3-d]pyrimidin-6-yl)-2-cyanoacrylate
PDB Id:  4D9T
Resolution:  2.4Å
Species:  Human
References:  9
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 Affinity Parameter Reference
BIX 02565 Hs Inhibition 9.0 pIC50 7
pIC50 9.0 (IC50 1.1x10-9 M) [7]
compound 8h [PMID: 22765894] Hs Inhibition 8.5 pIC50 6
pIC50 8.5 (IC50 3x10-9 M) [6]
compound 25b [PMID: 22564207] Hs Inhibition 7.9 pIC50 5
pIC50 7.9 (IC50 1.3x10-8 M) [5]
FMK Hs Inhibition 7.8 pIC50 2
pIC50 7.8 (IC50 1.5x10-8 M) [2]
BI-D1870 Hs Inhibition 7.6 pIC50 8
pIC50 7.6 (IC50 2.4x10-8 M) [8]
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: 3,10

Key to terms and symbols Click column headers to sort
Target used in screen: RSK2(Kin.Dom.1-N-terminal)
Ligand Sp. Type Action Affinity Parameter
NVP-TAE684 Hs Inhibitor Inhibition 7.8 pKd
staurosporine Hs Inhibitor Inhibition 7.2 pKd
enzastaurin Hs Inhibitor Inhibition 7.1 pKd
GSK-1838705A Hs Inhibitor Inhibition 6.8 pKd
GSK-461364A Hs Inhibitor Inhibition 6.7 pKd
PP-242 Hs Inhibitor Inhibition 6.7 pKd
KW-2449 Hs Inhibitor Inhibition 6.6 pKd
lestaurtinib Hs Inhibitor Inhibition 6.5 pKd
JNJ-28312141 Hs Inhibitor Inhibition 6.4 pKd
sunitinib Hs Inhibitor Inhibition 6.2 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: Rsk2/RSK2
Ligand Sp. Type Action % Activity remaining at 0.5µM % Activity remaining at 1µM % Activity remaining at 10µM
staurosporine Hs Inhibitor Inhibition -1.3 0.0 0.0
Cdk1/2 inhibitor III Hs Inhibitor Inhibition -0.7 0.0 -1.0
Ro-32-0432 Hs Inhibitor Inhibition 1.8
SB 218078 Hs Inhibitor Inhibition 2.3 11.0 3.0
GF109203X Hs Inhibitor Inhibition 2.5 1.0 1.0
K-252a Hs Inhibitor Inhibition 2.6 1.0 1.0
midostaurin Hs Inhibitor Inhibition 3.2 1.0 0.0
PKCbeta inhibitor Hs Inhibitor Inhibition 3.8 3.0 1.0
Gö 6976 Hs Inhibitor Inhibition 5.9 1.0 1.0
Gö 6983 Hs Inhibitor Inhibition 6.6 2.0 -1.0
Displaying the top 10 most potent ligands  View all ligands in screen »
Clinically-Relevant Mutations and Pathophysiology
Disease:  Coffin-Lowry syndrome
Disease Ontology: DOID:3783
OMIM: 303600
Orphanet: ORPHA192
Disease:  Mental retardation, X-linked 19; MRX19
Synonyms: Non-specific X-linked mental retardation [Disease Ontology: DOID:0050776]
X-linked non-syndromic intellectual disability [Orphanet: ORPHA777]
Disease Ontology: DOID:0050776
OMIM: 300844
Orphanet: ORPHA777

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. Cohen MS, Hadjivassiliou H, Taunton J. (2007) A clickable inhibitor reveals context-dependent autoactivation of p90 RSK. Nat. Chem. Biol., 3 (3): 156-60. [PMID:17259979]

3. 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]

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. Gingrich DE, Lisko JG, Curry MA, Cheng M, Quail M, Lu L, Wan W, Albom MS, Angeles TS, Aimone LD et al.. (2012) Discovery of an orally efficacious inhibitor of anaplastic lymphoma kinase. J. Med. Chem., 55 (10): 4580-93. [PMID:22564207]

6. Kim MH, Tsuhako AL, Co EW, Aftab DT, Bentzien F, Chen J, Cheng W, Engst S, Goon L, Klein RR et al.. (2012) The design, synthesis, and biological evaluation of potent receptor tyrosine kinase inhibitors. Bioorg. Med. Chem. Lett., 22 (15): 4979-85. [PMID:22765894]

7. Kirrane TM, Boyer SJ, Burke J, Guo X, Snow RJ, Soleymanzadeh L, Swinamer A, Zhang Y, Madwed JB, Kashem M et al.. (2012) Indole RSK inhibitors. Part 2: optimization of cell potency and kinase selectivity. Bioorg. Med. Chem. Lett., 22 (1): 738-42. [PMID:22056746]

8. 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]

9. Serafimova IM, Pufall MA, Krishnan S, Duda K, Cohen MS, Maglathlin RL, McFarland JM, Miller RM, Frödin M, Taunton J. (2012) Reversible targeting of noncatalytic cysteines with chemically tuned electrophiles. Nat. Chem. Biol., 8 (5): 471-6. [PMID:22466421]

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

RSK subfamily: ribosomal protein S6 kinase A3. Last modified on 04/11/2016. Accessed on 23/05/2019. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1528.