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serum/glucocorticoid regulated kinase 1

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Immunopharmacology Ligand target has curated data in GtoImmuPdb

Target id: 1534

Nomenclature: serum/glucocorticoid regulated kinase 1

Abbreviated Name: SGK1

Family: SGK family

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 431 6q23.2 SGK1 serum/glucocorticoid regulated kinase 1
Mouse - 431 10 A3 Sgk1 serum/glucocorticoid regulated kinase 1
Rat - 430 1p12 Sgk1 serum/glucocorticoid regulated kinase 1
Previous and Unofficial Names Click here for help
serine/threonine-protein kinase Sgk1
Database Links Click here for help
BRENDA
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
KEGG Gene
OMIM
Pharos
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of the kinase domain of serum and glucocorticoid-regulated kinase 1 in complex with AMP-PNP.
PDB Id:  2R5T
Ligand:  AMP-PNP
Resolution:  1.9Å
Species:  Human
References:  8
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
compound 14n [PMID: 25589934] Small molecule or natural product Click here for species-specific activity table Hs Inhibition 9.0 pIC50 4
pIC50 9.0 (IC50 1x10-9 M) [4]
Description: at low (10μM) ATP concentration
PO-322 Small molecule or natural product Immunopharmacology Ligand Hs Inhibition 7.3 pIC50 5
pIC50 7.3 (IC50 5.4x10-8 M) [5]
GSK650394 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.2 pIC50 6
pIC50 7.2 (IC50 6.2x10-8 M) [6]
EMD638683 Small molecule or natural product Primary target of this compound Hs Inhibition 5.5 pIC50 1
pIC50 5.5 (IC50 3x10-6 M) [1]
Description: In vitro testing
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: 2-3

Key to terms and symbols Click column headers to sort
Target used in screen: SGK/SGK1
Ligand Sp. Type Action % Activity remaining at 0.5µM % Activity remaining at 1µM % Activity remaining at 10µM
K-252a Small molecule or natural product Hs Inhibitor Inhibition 8.0 4.0 1.0
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 8.6 5.5 1.0
SB 218078 Small molecule or natural product Hs Inhibitor Inhibition 23.8 53.0 43.0
PKR inhibitor Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 24.7 31.0 7.0
JAK3 inhibitor VI Small molecule or natural product Hs Inhibitor Inhibition 26.0 25.0 1.0
Cdk4 inhibitor Small molecule or natural product Hs Inhibitor Inhibition 47.6 44.0 50.0
GF109203X Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 48.6 60.0 13.0
Cdk1/2 inhibitor III Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 48.7 53.0 16.0
SU11652 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 49.6 59.0 23.0
JAK inhibitor I Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 50.9 63.0 68.0
Displaying the top 10 most potent ligands  View all ligands in screen »
Immunopharmacology Comments
SGK1 is critical for the development and function of Th17 cells and restrains the function of Foxp3+ Treg cells. These reciprocal effects regulate Th17/Treg balance [7].
Physiological Consequences of Altering Gene Expression Click here for help
Sgk1 deficiency in Treg cells leads to protection against autoimmunity and enhances self-tolerance.
Species:  Mouse
Tissue: 
Technique: 
References:  7

References

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1. Ackermann TF, Boini KM, Beier N, Scholz W, Fuchss T, Lang F. (2011) EMD638683, a novel SGK inhibitor with antihypertensive potency. Cell. Physiol. Biochem., 28 (1): 137-46. [PMID:21865856]

2. 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]

3. 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]

4. Halland N, Schmidt F, Weiss T, Saas J, Li Z, Czech J, Dreyer M, Hofmeister A, Mertsch K, Dietz U et al.. (2015) Discovery of N-[4-(1H-Pyrazolo[3,4-b]pyrazin-6-yl)-phenyl]-sulfonamides as Highly Active and Selective SGK1 Inhibitors. ACS Med Chem Lett, 6 (1): 73-8. [PMID:25589934]

5. Lai Y, Luo XY, Guo HJ, Wang SY, Xiong J, Yang SX, Li LM, Zou Q, Mo CF, Wang YT et al.. (2020) PO-322 exerts potent immunosuppressive effects in vitro and in vivo by selectively inhibiting SGK1 activity. Br. J. Pharmacol., 177 (7): 1666-1676. [PMID:31724152]

6. Sherk AB, Frigo DE, Schnackenberg CG, Bray JD, Laping NJ, Trizna W, Hammond M, Patterson JR, Thompson SK, Kazmin D et al.. (2008) Development of a small-molecule serum- and glucocorticoid-regulated kinase-1 antagonist and its evaluation as a prostate cancer therapeutic. Cancer Res., 68 (18): 7475-83. [PMID:18794135]

7. Wu C, Chen Z, Xiao S, Thalhamer T, Madi A, Han T, Kuchroo V. (2018) SGK1 Governs the Reciprocal Development of Th17 and Regulatory T Cells. Cell Rep, 22 (3): 653-665. [PMID:29346764]

8. Zhao B, Lehr R, Smallwood AM, Ho TF, Maley K, Randall T, Head MS, Koretke KK, Schnackenberg CG. (2007) Crystal structure of the kinase domain of serum and glucocorticoid-regulated kinase 1 in complex with AMP PNP. Protein Sci., 16 (12): 2761-9. [PMID:17965184]

How to cite this page

SGK family: serum/glucocorticoid regulated kinase 1. Last modified on 03/04/2020. Accessed on 01/12/2020. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1534.