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p21 (RAC1) activated kinase 2

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Immunopharmacology Ligand  Target has curated data in GtoImmuPdb

Target id: 2134

Nomenclature: p21 (RAC1) activated kinase 2

Abbreviated Name: PAK2

Family: PAKA subfamily

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 524 3q29 PAK2 p21 (RAC1) activated kinase 2
Mouse - 524 16 22.4 cM Pak2 p21 (RAC1) activated kinase 2
Rat - 524 11q22 Pak2 p21 (RAC1) activated kinase 2
Previous and Unofficial Names Click here for help
gamma-PAK | p21 (CDKN1A)-activated kinase 2 | p21-activated kinase 2 | PAK65 | S6/H4 kinase | p21 protein (Cdc42/Rac)-activated kinase 2
Database Links Click here for help
Alphafold Q13177 (Hs), Q8CIN4 (Mm), Q64303 (Rn)
BRENDA 2.7.11.1
CATH/Gene3D 3.90.810.10
ChEMBL Target CHEMBL4487 (Hs)
Ensembl Gene ENSG00000180370 (Hs), ENSMUSG00000022781 (Mm), ENSRNOG00000001747 (Rn)
Entrez Gene 5062 (Hs), 224105 (Mm), 29432 (Rn)
Human Protein Atlas ENSG00000180370 (Hs)
KEGG Enzyme 2.7.11.1
KEGG Gene hsa:5062 (Hs), mmu:224105 (Mm), rno:29432 (Rn)
OMIM 605022 (Hs)
Pharos Q13177 (Hs)
RefSeq Nucleotide NM_002577 (Hs), NM_177326 (Mm), NM_053306 (Rn)
RefSeq Protein NP_002568 (Hs), NP_796300 (Mm), NP_445758 (Rn)
UniProtKB Q13177 (Hs), Q8CIN4 (Mm), Q64303 (Rn)
Wikipedia PAK2 (Hs)
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  Structure of EspG-PAK2 autoinhibitory Ialpha3 helix complex
PDB Id:  3PCS
Resolution:  2.86Å
Species:  Human
References:  10
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
staurosporine Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 9.0 pIC50 6
⤷ pIC50 9.0 (IC50 1x10-9 M) [6]
PQA-18 Small molecule or natural product Immunopharmacology Ligand Hs Inhibition 8.0 pIC50 9
⤷ pIC50 8.0 (IC50 1x10-8 M) [9]
Description: Using immunoprecipitated PAK2 and histone H4 substrate from Jurkat cells.
FRAX597 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.9 pIC50 8
⤷ pIC50 7.9 (IC50 1.3x10-8 M) [8]
FRAX486 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.4 pIC50 4
⤷ pIC50 7.4 (IC50 3.95x10-8 M) [4]
Il-94 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.2 pIC50 1
⤷ pIC50 7.2 (IC50 6.41x10-8 M) [1]
PF-3758309 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 6.7 pIC50 7
⤷ pIC50 6.7 (IC50 1.9x10-7 M) [7]
compound 4 [PMID: 24432870] Small molecule or natural product Click here for species-specific activity table Hs Inhibition 6.0 pIC50 7
⤷ pIC50 6.0 (IC50 9.7x10-7 M) [7]
Allosteric Modulators
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
compound 3 [PMID: 26191365] Small molecule or natural product Click here for species-specific activity table Hs Negative 6.4 pKd 7
⤷ pKd 6.4 (Kd 4x10-7 M) [7]
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: 3,11
Key to terms and symbols Click column headers to sort
Target used in screen: PAK2
Ligand Sp. Type Action Value Parameter
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 8.5 pKd
lestaurtinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 7.4 pKd
neratinib Small molecule or natural product Approved drug Hs Inhibitor Inhibition 7.1 pKd
GSK690693 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.6 pKd
tamatinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 6.5 pKd
A-674563 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 5.8 pKd
bosutinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 5.7 pKd
KW-2449 Small molecule or natural product Hs Inhibitor Inhibition 5.6 pKd
SB203580 Small molecule or natural product Immunopharmacology Ligand Hs Inhibitor Inhibition <5.5 pKd
ruboxistaurin Small molecule or natural product Ligand has a PDB structure 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 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: 2,5
Key to terms and symbols Click column headers to sort
Target used in screen: PAK2/PAK2
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 0.7 5.5 -0.5
K-252a Small molecule or natural product Hs Inhibitor Inhibition 7.5 19.0 2.0
Cdk1/2 inhibitor III Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 26.4 47.0 7.0
alsterpaullone Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 41.0 43.0 30.0
SB 218078 Small molecule or natural product Hs Inhibitor Inhibition 43.9 91.0 101.0
alsterpaullone 2-cyanoethyl Small molecule or natural product Hs Inhibitor Inhibition 55.6 62.0 37.0
TGF-beta RI kinase inhibitor Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 57.0 107.0 88.0
AG 9 Small molecule or natural product Hs Inhibitor Inhibition 58.1 106.0 99.0
Syk inhibitor II Small molecule or natural product Immunopharmacology Ligand Hs Inhibitor Inhibition 58.9 101.0 83.0
semaxanib Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 66.5 108.0 111.0
Displaying the top 10 most potent ligands  View all ligands in screen »
Immunopharmacology Comments
Pharmacological inhibition of PAK2 has immunosuppressive effects [9].
Immuno Process Associations
Immuno Process:  Inflammation
Immuno Process:  Cytokine production & signalling
Immuno Process:  T cell (activation)
Immuno Process:  Immune regulation
Immuno Process:  Chemotaxis & migration
Immuno Process:  Cellular signalling

References

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1. Abdel-Magid AF. (2013) PAK1: A Therapeutic Target for Cancer Treatment. ACS Med Chem Lett, 4 (5): 431-2. [PMID:24900689]

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. 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]

4. 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]

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. Hall MD, Salam NK, Hellawell JL, Fales HM, Kensler CB, Ludwig JA, Szakács G, Hibbs DE, Gottesman MM. (2009) Synthesis, activity, and pharmacophore development for isatin-beta-thiosemicarbazones with selective activity toward multidrug-resistant cells. J Med Chem, 52 (10): 3191-204. [PMID:19397322]

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. Ogura M, Kikuchi H, Suzuki T, Yamaki J, Homma MK, Oshima Y, Homma Y. (2016) Prenylated quinolinecarboxylic acid derivative suppresses immune response through inhibition of PAK2. Biochem Pharmacol, 105: 55-65. [PMID:26827943]

10. Selyunin AS, Sutton SE, Weigele BA, Reddick LE, Orchard RC, Bresson SM, Tomchick DR, Alto NM. (2011) The assembly of a GTPase-kinase signalling complex by a bacterial catalytic scaffold. Nature, 469 (7328): 107-11. [PMID:21170023]

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

PAKA subfamily: p21 (RAC1) activated kinase 2. Last modified on 15/02/2017. Accessed on 18/04/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetoimmunopharmacology.org/GRAC/ObjectDisplayForward?objectId=2134.