ribosomal protein S6 kinase B1 | p70 subfamily | IUPHAR/BPS Guide to PHARMACOLOGY

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ribosomal protein S6 kinase B1

Target not currently curated in GtoImmuPdb

Target id: 1525

Nomenclature: ribosomal protein S6 kinase B1

Abbreviated Name: p70S6K

Family: p70 subfamily

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 525 17q23.1 RPS6KB1 ribosomal protein S6 kinase B1
Mouse - 525 11 Rps6kb1 ribosomal protein S6 kinase
Rat - 525 10q26 Rps6kb1 ribosomal protein S6 kinase B1
Previous and Unofficial Names
S6Kβ1 | ribosomal protein S6 kinase, 70kD, polypeptide 1 | 70 kDa ribosomal protein S6 kinase 1 | p70 ribosomal S6 kinase alpha | ribosomal protein S6 kinase beta-1 | ribosomal protein S6 kinase I | S6 kinase | STK14A | ribosomal protein S6 kinase, polypeptide 1 | ribosomal protein S6 kinase
Database Links
BRENDA
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
KEGG Gene
OMIM
Pharos
RefSeq Nucleotide
RefSeq Protein
SynPHARM
UniProtKB
Wikipedia
Selected 3D Structures
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of phosphorylated p70S6K1
PDB Id:  3A62
Resolution:  2.35Å
Species:  Human
References:  8
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
LY2584702 Hs Inhibition 8.4 pIC50 9
pIC50 8.4 (IC50 4x10-9 M) [9]
compound 1 [PMID: 20005102] Hs Inhibition 8.1 pIC50 6
pIC50 8.1 (IC50 7x10-9 M) [6]
compound E22 [PMID: 31298542] Hs Inhibition 8.1 pIC50 3
pIC50 8.1 (IC50 8.9x10-9 M) [3]
PF-4708671 Hs Inhibition 7.7 pIC50 7
pIC50 7.7 (IC50 2x10-8 M) [7]
Description: In vitro assay of full length RPS6KB1.
GNE-3511 Hs Inhibition 5.7 pIC50 5
pIC50 5.7 (IC50 1.94x10-6 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: 2,10

Key to terms and symbols Click column headers to sort
Target used in screen: S6K1
Ligand Sp. Type Action Value Parameter
staurosporine Hs Inhibitor Inhibition 8.9 pKd
sunitinib Hs Inhibitor Inhibition 7.3 pKd
lestaurtinib Hs Inhibitor Inhibition 7.2 pKd
AST-487 Hs Inhibitor Inhibition 6.9 pKd
SU-14813 Hs Inhibitor Inhibition 6.8 pKd
ruboxistaurin Hs Inhibitor Inhibition 6.7 pKd
KW-2449 Hs Inhibitor Inhibition 6.5 pKd
dovitinib Hs Inhibitor Inhibition 6.2 pKd
crizotinib Hs Inhibitor Inhibition 6.2 pKd
bosutinib 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: p70S6K/p70S6K(RPS6KB1)
Ligand Sp. Type Action % Activity remaining at 0.5µM % Activity remaining at 1µM % Activity remaining at 10µM
staurosporine Hs Inhibitor Inhibition 0.1 1.5 3.0
SB 218078 Hs Inhibitor Inhibition 2.4 51.0 31.0
Gö 6976 Hs Inhibitor Inhibition 6.7 1.0 4.0
K-252a Hs Inhibitor Inhibition 7.2 6.0 1.0
GF109203X Hs Inhibitor Inhibition 11.6 11.0 2.0
midostaurin Hs Inhibitor Inhibition 19.4 4.0 1.0
Gö 6983 Hs Inhibitor Inhibition 19.7 22.0 2.0
Ro-32-0432 Hs Inhibitor Inhibition 20.0
H-89 Hs Inhibitor Inhibition 25.6 13.0 5.0
JAK3 inhibitor VI Hs Inhibitor Inhibition 26.6 8.0 2.0
Displaying the top 10 most potent ligands  View all ligands in screen »
Immuno Process Associations
Immuno Process:  Inflammation
GO Annotations:  Associated to 1 GO processes, IEA only
click arrow to show/hide IEA associations
GO:0071346 cellular response to interferon-gamma IEA
Immuno Process:  Cytokine production & signalling
GO Annotations:  Associated to 2 GO processes, IEA only
click arrow to show/hide IEA associations
GO:0034612 response to tumor necrosis factor IEA
GO:0071346 cellular response to interferon-gamma IEA

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. 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. Lin H, Yamashita DS, Zeng J, Xie R, Verma S, Luengo JI, Rhodes N, Zhang S, Robell KA, Choudhry AE et al.. (2010) 2,3,5-Trisubstituted pyridines as selective AKT inhibitors. Part II: Improved drug-like properties and kinase selectivity from azaindazoles. Bioorg. Med. Chem. Lett., 20 (2): 679-83. [PMID:20005102]

7. Pearce LR, Alton GR, Richter DT, Kath JC, Lingardo L, Chapman J, Hwang C, Alessi DR. (2010) Characterization of PF-4708671, a novel and highly specific inhibitor of p70 ribosomal S6 kinase (S6K1). Biochem. J., 431 (2): 245-55. [PMID:20704563]

8. Sunami T, Byrne N, Diehl RE, Funabashi K, Hall DL, Ikuta M, Patel SB, Shipman JM, Smith RF, Takahashi I et al.. (2010) Structural basis of human p70 ribosomal S6 kinase-1 regulation by activation loop phosphorylation. J. Biol. Chem., 285 (7): 4587-94. [PMID:19864428]

9. Tolcher A, Goldman J, Patnaik A, Papadopoulos KP, Westwood P, Kelly CS, Bumgardner W, Sams L, Geeganage S, Wang T et al.. (2014) A phase I trial of LY2584702 tosylate, a p70 S6 kinase inhibitor, in patients with advanced solid tumours. Eur. J. Cancer, 50 (5): 867-75. [PMID:24440085]

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

p70 subfamily: ribosomal protein S6 kinase B1. Last modified on 25/07/2019. Accessed on 26/09/2020. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1525.