Top ▲

ribosomal protein S6 kinase B1

Click here for help

Target not currently curated in GtoImmuPdb

Target id: 1525

Nomenclature: ribosomal protein S6 kinase B1

Abbreviated Name: p70S6K

Family: p70 subfamily

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 525 17q23.1 RPS6KB1 ribosomal protein S6 kinase B1
Mouse - 525 11 C Rps6kb1 ribosomal protein S6 kinase, polypeptide 1
Rat - 525 10q26 Rps6kb1 ribosomal protein S6 kinase B1
Previous and Unofficial Names Click here for help
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 Click here for help
Alphafold P23443 (Hs), Q8BSK8 (Mm), P67999 (Rn)
BRENDA 2.7.11.1
ChEMBL Target CHEMBL4501 (Hs), CHEMBL5429 (Mm)
Ensembl Gene ENSG00000108443 (Hs), ENSMUSG00000020516 (Mm), ENSRNOG00000003919 (Rn)
Entrez Gene 6198 (Hs), 72508 (Mm), 83840 (Rn)
Human Protein Atlas ENSG00000108443 (Hs)
KEGG Enzyme 2.7.11.1
KEGG Gene hsa:6198 (Hs), mmu:72508 (Mm), rno:83840 (Rn)
OMIM 608938 (Hs)
Pharos P23443 (Hs)
RefSeq Nucleotide NM_003161 (Hs), NM_001114334 (Mm), NM_031985 (Rn)
RefSeq Protein NP_003152 (Hs), NP_001107806 (Mm), NP_082535 (Mm), NP_114191 (Rn)
SynPHARM 81034 (in complex with PF-4708671)
UniProtKB P23443 (Hs), Q8BSK8 (Mm), P67999 (Rn)
Wikipedia RPS6KB1 (Hs)
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of phosphorylated p70S6K1
PDB Id:  3A62
Resolution:  2.35Å
Species:  Human
References:  11
Enzyme Reaction Click here for help
EC Number: 2.7.11.1

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
rupitasertib Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 9.0 pIC50 9
⤷ pIC50 9.0 (IC50 1x10-9 M) [9]
LY2584702 Small molecule or natural product Primary target of this compound Hs Inhibition 8.4 pIC50 12
⤷ pIC50 8.4 (IC50 4x10-9 M) [12]
compound 1 [PMID: 20005102] Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 8.1 pIC50 8
⤷ pIC50 8.1 (IC50 7x10-9 M) [8]
compound E22 [PMID: 31298542] Small molecule or natural product Click here for species-specific activity table Hs Inhibition 8.1 pIC50 5
⤷ pIC50 8.1 (IC50 8.9x10-9 M) [5]
PF-4708671 Small molecule or natural product Primary target of this compound Ligand has a PDB structure Hs Inhibition 7.7 pIC50 10
⤷ pIC50 7.7 (IC50 2x10-8 M) [10]
Description: In vitro assay of full length RPS6KB1.
Sanofi-14h Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 7.1 pIC50 2
⤷ pIC50 7.1 (IC50 7.6x10-8 M) [2]
GNE-3511 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 5.7 pIC50 7
⤷ pIC50 5.7 (IC50 1.94x10-6 M) [7]
GLXC-26326 Small molecule or natural product Hs Inhibition - - 3
⤷ [3]
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: 4,13
Key to terms and symbols Click column headers to sort
Target used in screen: S6K1
Ligand Sp. Type Action Value Parameter
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 8.9 pKd
sunitinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 7.3 pKd
lestaurtinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 7.2 pKd
AST-487 Small molecule or natural product Hs Inhibitor Inhibition 6.9 pKd
SU-14813 Small molecule or natural product Hs Inhibitor Inhibition 6.8 pKd
ruboxistaurin Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.7 pKd
KW-2449 Small molecule or natural product Hs Inhibitor Inhibition 6.5 pKd
dovitinib Small molecule or natural product Hs Inhibitor Inhibition 6.2 pKd
crizotinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 6.2 pKd
bosutinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand 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 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: 1,6
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 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 0.1 1.5 3.0
SB 218078 Small molecule or natural product Hs Inhibitor Inhibition 2.4 51.0 31.0
Gö 6976 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.7 1.0 4.0
K-252a Small molecule or natural product Hs Inhibitor Inhibition 7.2 6.0 1.0
GF109203X Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 11.6 11.0 2.0
midostaurin Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 19.4 4.0 1.0
Gö 6983 Small molecule or natural product Hs Inhibitor Inhibition 19.7 22.0 2.0
Ro-32-0432 Small molecule or natural product Hs Inhibitor Inhibition 20.0
H-89 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 25.6 13.0 5.0
JAK3 inhibitor VI Small molecule or natural product 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
Immuno Process:  Cytokine production & signalling

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. Bago R, Sommer E, Castel P, Crafter C, Bailey FP, Shpiro N, Baselga J, Cross D, Eyers PA, Alessi DR. (2016) The hVps34-SGK3 pathway alleviates sustained PI3K/Akt inhibition by stimulating mTORC1 and tumour growth. EMBO J, 35 (17): 1902-22. [PMID:27481935]

3. Dally RD, Joseph S, Shepherd TA. (2010) Akt and p70 s6 kinase inhibitors. Patent number: WO2010056563A1. Assignee: Eli Lilly And Company. Priority date: 03/11/2009. Publication date: 20/05/2010.

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. 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]

6. 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]

7. 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]

8. 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]

9. Machl A, Wilker EW, Tian H, Liu X, Schroeder P, Clark A, Huck BR. (2016) M2698 is a potent dual-inhibitor of p70S6K and Akt that affects tumor growth in mouse models of cancer and crosses the blood-brain barrier. Am J Cancer Res, 6 (4): 806-18. [PMID:27186432]

10. 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]

11. 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]

12. 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]

13. 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 04/01/2024. Accessed on 20/04/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1525.