Protein kinase G (PKG) 1 | Protein kinase G (PKG) family | IUPHAR/BPS Guide to PHARMACOLOGY

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Protein kinase G (PKG) 1

Target not currently curated in GtoImmuPdb

Target id: 1492

Nomenclature: Protein kinase G (PKG) 1

Abbreviated Name: PKG1

Family: Protein kinase G (PKG) family

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 - 671 10q11.2 PRKG1 protein kinase cGMP-dependent 1
Mouse - 671 19 C2 Prkg1 protein kinase
Rat - 671 1 q52 Prkg1 protein kinase cGMP-dependent 1
Previous and Unofficial Names
PGK | PKG | PRKG1B | PRKGR1B | cGk1 | Prkg1b | protein kinase | protein kinase, cGMP-dependent, type I
Database Links
BRENDA
CATH/Gene3D
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
KEGG Gene
OMIM
Orphanet
Pharos
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Selected 3D Structures
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of cAMP bound cGMP-dependent protein kinase(92-227)
PDB Id:  3OCP
Resolution:  2.49Å
Species:  Human
References:  7
Enzyme Reaction
EC Number: 2.7.11.12

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
GSK690693 Hs Inhibition 7.5 pIC50 6
pIC50 7.5 (IC50 3.3x10-8 M) [6]
ipatasertib Hs Inhibition 7.2 pIC50 2
pIC50 7.2 (IC50 6.9x10-8 M) [2]
Rp-8-CPT-cGMPS Hs Inhibition - - 3
[3]
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: 4,8

Key to terms and symbols Click column headers to sort
Target used in screen: PRKG1
Ligand Sp. Type Action Value Parameter
staurosporine Hs Inhibitor Inhibition 7.5 pKd
GSK690693 Hs Inhibitor Inhibition 6.7 pKd
midostaurin Hs Inhibitor Inhibition 6.6 pKd
A-674563 Hs Inhibitor Inhibition 6.6 pKd
lestaurtinib Hs Inhibitor Inhibition 6.4 pKd
NVP-TAE684 Hs Inhibitor Inhibition 6.4 pKd
enzastaurin Hs Inhibitor Inhibition 6.0 pKd
KW-2449 Hs Inhibitor Inhibition 5.6 pKd
SB203580 Hs Inhibitor Inhibition <5.5 pKd
ruboxistaurin Hs Inhibitor Inhibition <5.5 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: 1,5

Key to terms and symbols Click column headers to sort
Target used in screen: PKG1α/PKG1a
Ligand Sp. Type Action % Activity remaining at 0.5µM % Activity remaining at 1µM % Activity remaining at 10µM
staurosporine Hs Inhibitor Inhibition 5.0 3.0 3.0
midostaurin Hs Inhibitor Inhibition 8.4 8.0 4.0
K-252a Hs Inhibitor Inhibition 13.4 10.0 1.0
PKR inhibitor Hs Inhibitor Inhibition 17.5 13.0 2.0
H-89 Hs Inhibitor Inhibition 26.3 4.0 4.0
SB 218078 Hs Inhibitor Inhibition 35.7 84.0 73.0
GF109203X Hs Inhibitor Inhibition 38.3 60.0 14.0
JAK inhibitor I Hs Inhibitor Inhibition 40.2 45.0 45.0
indirubin derivative E804 Hs Inhibitor Inhibition 45.1 56.0 19.0
dorsomorphin Hs Inhibitor Inhibition 57.6 73.0 25.0
Target used in screen: PKG1β/PKG1b
Ligand Sp. Type Action % Activity remaining at 0.5µM % Activity remaining at 1µM % Activity remaining at 10µM
staurosporine Hs Inhibitor Inhibition 3.3 1.0 0.5
midostaurin Hs Inhibitor Inhibition 18.8 4.0 3.0
K-252a Hs Inhibitor Inhibition 19.1 9.0 2.0
PKR inhibitor Hs Inhibitor Inhibition 20.3 7.0 1.0
H-89 Hs Inhibitor Inhibition 41.1 4.0 4.0
SB 218078 Hs Inhibitor Inhibition 41.3 76.0 74.0
JAK inhibitor I Hs Inhibitor Inhibition 52.3 30.0 19.0
indirubin derivative E804 Hs Inhibitor Inhibition 53.0 44.0 9.0
JAK3 inhibitor VI Hs Inhibitor Inhibition 58.7 39.0 7.0
GF109203X Hs Inhibitor Inhibition 59.3 34.0 6.0
Displaying the top 10 most potent ligands  View all ligands in screen »
Clinically-Relevant Mutations and Pathophysiology
Disease:  Aortic aneurysm, familial thoracic 8; AAT8
Synonyms: Familial thoracic aortic aneurysm and aortic dissection [Orphanet: ORPHA91387]
thoracic aortic aneurysm
Disease Ontology: DOID:14004
OMIM: 615436
Orphanet: ORPHA91387

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. Blake JF, Xu R, Bencsik JR, Xiao D, Kallan NC, Schlachter S, Mitchell IS, Spencer KL, Banka AL, Wallace EM et al.. (2012) Discovery and preclinical pharmacology of a selective ATP-competitive Akt inhibitor (GDC-0068) for the treatment of human tumors. J. Med. Chem., 55 (18): 8110-27. [PMID:22934575]

3. Butt E, Eigenthaler M, Genieser HG. (1994) (Rp)-8-pCPT-cGMPS, a novel cGMP-dependent protein kinase inhibitor. Eur. J. Pharmacol., 269 (2): 265-8. [PMID:7851503]

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. 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]

6. Heerding DA, Rhodes N, Leber JD, Clark TJ, Keenan RM, Lafrance LV, Li M, Safonov IG, Takata DT, Venslavsky JW et al.. (2008) Identification of 4-(2-(4-amino-1,2,5-oxadiazol-3-yl)-1-ethyl-7-{[(3S)-3-piperidinylmethyl]oxy}-1H-imidazo[4,5-c]pyridin-4-yl)-2-methyl-3-butyn-2-ol (GSK690693), a novel inhibitor of AKT kinase. J. Med. Chem., 51 (18): 5663-79. [PMID:18800763]

7. Kim JJ, Casteel DE, Huang G, Kwon TH, Ren RK, Zwart P, Headd JJ, Brown NG, Chow DC, Palzkill T et al.. (2011) Co-crystal structures of PKG Iβ (92-227) with cGMP and cAMP reveal the molecular details of cyclic-nucleotide binding. PLoS ONE, 6 (4): e18413. [PMID:21526164]

8. 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

Protein kinase G (PKG) family: Protein kinase G (PKG) 1. Last modified on 07/02/2019. Accessed on 07/04/2020. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1492.