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p21 (RAC1) activated kinase 4

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Target not currently curated in GtoImmuPdb

Target id: 2136

Nomenclature: p21 (RAC1) activated kinase 4

Abbreviated Name: PAK4

Family: PAKB subfamily

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 591 19q13.2 PAK4 p21 (RAC1) activated kinase 4
Mouse - 593 7 B1 Pak4 p21 (RAC1) activated kinase 4
Rat - 593 1 q21 Pak4 p21 (RAC1) activated kinase 4
Previous and Unofficial Names Click here for help
p21 (CDKN1A)-activated kinase 4 | p21-activated kinase 4 | p21 protein (Cdc42/Rac)-activated kinase 4
Database Links Click here for help
Alphafold O96013 (Hs), Q8BTW9 (Mm)
BRENDA 2.7.11.1
CATH/Gene3D 3.90.810.10
ChEMBL Target CHEMBL4482 (Hs)
Ensembl Gene ENSG00000130669 (Hs), ENSMUSG00000030602 (Mm), ENSRNOG00000019883 (Rn)
Entrez Gene 10298 (Hs), 70584 (Mm), 292756 (Rn)
Human Protein Atlas ENSG00000130669 (Hs)
KEGG Enzyme 2.7.11.1
KEGG Gene hsa:10298 (Hs), mmu:70584 (Mm), rno:292756 (Rn)
OMIM 605451 (Hs)
Pharos O96013 (Hs)
RefSeq Nucleotide NM_001014831 (Hs), NM_027470 (Mm), NM_001106238 (Rn)
RefSeq Protein NP_001014831 (Hs), NP_081746 (Mm), NP_001099708 (Rn)
UniProtKB O96013 (Hs), Q8BTW9 (Mm)
Wikipedia PAK4 (Hs)
Selected 3D Structures Click here for help
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:  5
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 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
PF-3758309 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.8 pKi 10
⤷ pKi 7.8 (Ki 1.5x10-8 M) [10]
compound 4 [PMID: 24432870] Small molecule or natural product Click here for species-specific activity table Hs Inhibition 8.1 pIC50 8
⤷ pIC50 8.1 (IC50 7.5x10-9 M) [8]
GSK690693 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 8.0 pIC50 7
⤷ pIC50 8.0 (IC50 1x10-8 M) [7]
Description: Data from binding assays.
AMG28 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.0 pIC50 4
⤷ pIC50 7.0 (IC50 1.1x10-7 M) [4]
FRAX486 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 6.1 pIC50 3
⤷ pIC50 6.1 (IC50 7.79x10-7 M) [3]
FRAX597 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition <5.0 pIC50 9
⤷ pIC50 <5.0 (IC50 >1x10-5 M) [9]
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: 2,11
Key to terms and symbols Click column headers to sort
Target used in screen: PAK4
Ligand Sp. Type Action Value Parameter
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 8.2 pKd
GSK690693 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 7.7 pKd
lestaurtinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 7.6 pKd
tamatinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 7.0 pKd
A-674563 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.0 pKd
PP-242 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.0 pKd
SU-14813 Small molecule or natural product Hs Inhibitor Inhibition 5.9 pKd
KW-2449 Small molecule or natural product Hs Inhibitor Inhibition 5.8 pKd
JNJ-28312141 Small molecule or natural product Hs Inhibitor Inhibition 5.8 pKd
ruxolitinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand 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 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: PAK4/PAK4
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 4.9 0.0 0.0
K-252a Small molecule or natural product Hs Inhibitor Inhibition 39.5 3.0 0.0
Gö 6976 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 44.0 3.0 2.0
Cdk1/2 inhibitor III Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 47.6 6.0 0.0
Cdk2 inhibitor IV Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 51.5 18.0 2.0
Syk inhibitor II Small molecule or natural product Immunopharmacology Ligand Hs Inhibitor Inhibition 69.3 49.0 9.0
VEGF receptor 2 kinase inhibitor I Small molecule or natural product Hs Inhibitor Inhibition 71.8 90.0 94.0
semaxanib Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 72.3 91.0 69.0
VEGF receptor 2 kinase inhibitor IV Small molecule or natural product Hs Inhibitor Inhibition 72.5 99.0 94.0
SB 218078 Small molecule or natural product 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 USA, 110 (14): 5671-6. [PMID:23509247]

4. Drewry DH, Potjewyd FM, Bayati A, Smith JL, Dickmander RJ, Howell S, Taft-Benz S, Min SM, Hossain MA, Heise M et al.. (2022) Identification and Utilization of a Chemical Probe to Interrogate the Roles of PIKfyve in the Lifecycle of β-Coronaviruses. J Med Chem, 65 (19): 12860-12882. [PMID:36111834]

5. 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]

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. 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]

8. 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]

9. 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]

10. 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]

11. 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 20/09/2022. Accessed on 24/04/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetoimmunopharmacology.org/GRAC/ObjectDisplayForward?objectId=2136.