p21 (RAC1) activated kinase 4 | PAKB subfamily | IUPHAR/BPS Guide to PHARMACOLOGY

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p21 (RAC1) activated kinase 4

Target not currently curated in GtoImmuPdb

Target id: 2136

Nomenclature: p21 (RAC1) activated kinase 4

Abbreviated Name: PAK4

Family: PAKB 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 - 591 19p11-q11 PAK4 p21 (RAC1) activated kinase 4
Mouse - 593 7 A3 Pak4 p21 (RAC1) activated kinase 4
Rat - 593 1 q21 Pak4 p21 (RAC1) activated kinase 4
Previous and Unofficial Names
p21 (CDKN1A)-activated kinase 4 | p21-activated kinase 4 | p21 protein (Cdc42/Rac)-activated kinase 4
Database Links
BRENDA
CATH/Gene3D
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
KEGG Gene
OMIM
Pharos
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Selected 3D Structures
Image of receptor 3D structure from RCSB PDB
Description:  CRYSTAL STRUCTURE OF THE HUMAN P21-ACTIVATED KINASE 4
PDB Id:  2BVA
Resolution:  2.3Å
Species:  Human
References:  4
Image of receptor 3D structure from RCSB PDB
Description:  Structure of human p21 activating kinase 4 (PAK4) in complex with a consensus peptide
PDB Id:  2Q0N
Resolution:  1.75Å
Species:  Human
References: 
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
PF-3758309 Hs Inhibition 7.8 pKi 9
pKi 7.8 (Ki 1.5x10-8 M) [9]
compound 4 [PMID: 24432870] Hs Inhibition 8.1 pIC50 7
pIC50 8.1 (IC50 7.5x10-9 M) [7]
GSK690693 Hs Inhibition 8.0 pIC50 6
pIC50 8.0 (IC50 1x10-8 M) [6]
Description: Data from binding assays.
FRAX486 Hs Inhibition 6.1 pIC50 3
pIC50 6.1 (IC50 7.79x10-7 M) [3]
FRAX597 Hs Inhibition <5.0 pIC50 8
pIC50 <5.0 (IC50 >1x10-5 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: 2,10

Key to terms and symbols Click column headers to sort
Target used in screen: PAK4
Ligand Sp. Type Action Value Parameter
staurosporine Hs Inhibitor Inhibition 8.2 pKd
GSK690693 Hs Inhibitor Inhibition 7.7 pKd
lestaurtinib Hs Inhibitor Inhibition 7.6 pKd
tamatinib Hs Inhibitor Inhibition 7.0 pKd
A-674563 Hs Inhibitor Inhibition 6.0 pKd
PP-242 Hs Inhibitor Inhibition 6.0 pKd
SU-14813 Hs Inhibitor Inhibition 5.9 pKd
KW-2449 Hs Inhibitor Inhibition 5.8 pKd
JNJ-28312141 Hs Inhibitor Inhibition 5.8 pKd
ruxolitinib Hs Inhibitor Inhibition 5.8 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: PAK4/PAK4
Ligand Sp. Type Action % Activity remaining at 0.5µM % Activity remaining at 1µM % Activity remaining at 10µM
staurosporine Hs Inhibitor Inhibition 4.9 0.0 0.0
K-252a Hs Inhibitor Inhibition 39.5 3.0 0.0
Gö 6976 Hs Inhibitor Inhibition 44.0 3.0 2.0
Cdk1/2 inhibitor III Hs Inhibitor Inhibition 47.6 6.0 0.0
Cdk2 inhibitor IV Hs Inhibitor Inhibition 51.5 18.0 2.0
Syk inhibitor II Hs Inhibitor Inhibition 69.3 49.0 9.0
VEGF receptor 2 kinase inhibitor I Hs Inhibitor Inhibition 71.8 90.0 94.0
semaxanib Hs Inhibitor Inhibition 72.3 91.0 69.0
VEGF receptor 2 kinase inhibitor IV Hs Inhibitor Inhibition 72.5 99.0 94.0
SB 218078 Hs Inhibitor Inhibition 75.3 84.0 64.0
Displaying the top 10 most potent ligands  View all ligands in screen »

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. Dolan BM, Duron SG, Campbell DA, Vollrath B, Shankaranarayana Rao BS, Ko HY, Lin GG, Govindarajan A, Choi SY, Tonegawa S. (2013) Rescue of fragile X syndrome phenotypes in Fmr1 KO mice by the small-molecule PAK inhibitor FRAX486. Proc. Natl. Acad. Sci. U.S.A., 110 (14): 5671-6. [PMID:23509247]

4. Eswaran J, Lee WH, Debreczeni JE, Filippakopoulos P, Turnbull A, Fedorov O, Deacon SW, Peterson JR, Knapp S. (2007) Crystal Structures of the p21-activated kinases PAK4, PAK5, and PAK6 reveal catalytic domain plasticity of active group II PAKs. Structure, 15 (2): 201-13. [PMID:17292838]

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. Karpov AS, Amiri P, Bellamacina C, Bellance MH, Breitenstein W, Daniel D, Denay R, Fabbro D, Fernandez C, Galuba I et al.. (2015) Optimization of a Dibenzodiazepine Hit to a Potent and Selective Allosteric PAK1 Inhibitor. ACS Med Chem Lett, 6 (7): 776-81. [PMID:26191365]

8. Licciulli S, Maksimoska J, Zhou C, Troutman S, Kota S, Liu Q, Duron S, Campbell D, Chernoff J, Field J et al.. (2013) FRAX597, a small molecule inhibitor of the p21-activated kinases, inhibits tumorigenesis of neurofibromatosis type 2 (NF2)-associated Schwannomas. J. Biol. Chem., 288 (40): 29105-14. [PMID:23960073]

9. Staben ST, Feng JA, Lyle K, Belvin M, Boggs J, Burch JD, Chua CC, Cui H, DiPasquale AG, Friedman LS et al.. (2014) Back pocket flexibility provides group II p21-activated kinase (PAK) selectivity for type I 1/2 kinase inhibitors. J. Med. Chem., 57 (3): 1033-45. [PMID:24432870]

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

PAKB subfamily: p21 (RAC1) activated kinase 4. Last modified on 03/12/2015. Accessed on 05/08/2020. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2136.