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AP2 associated kinase 1

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Target id: 1921

Nomenclature: AP2 associated kinase 1

Abbreviated Name: AAK1

Family: NAK family

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 961 2p13.3 AAK1 AP2 associated kinase 1
Mouse - 959 6 37.75 cM Aak1 AP2 associated kinase 1
Rat - 962 4q34 Aak1 AP2 associated kinase 1
Previous and Unofficial Names Click here for help
adaptor-associated kinase 1 | LMTK1
Database Links Click here for help
Alphafold
BRENDA
CATH/Gene3D
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
KEGG Gene
Pharos
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
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
baricitinib Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 7.8 pKd 5
pKd 7.8 (Kd 1.7x10-8 M) [5]
Description: Binding affinity determined in a cell-free biochemical assay.
BMS-986176 Small molecule or natural product Hs Inhibition 8.7 pIC50 4
pIC50 8.7 (IC50 2x10-9 M) [4]
compound 21b [PMID: 31136173] Small molecule or natural product Immunopharmacology Ligand Hs Inhibition 8.4 pIC50 6
pIC50 8.4 (IC50 4x10-9 M) [6]
Description: Inhibition of kinase activity in a LanthaScreen® assay.
BMS-911172 Small molecule or natural product Ligand has a PDB structure Hs Inhibition 7.9 pIC50 3
pIC50 7.9 (IC50 1.2x10-8 M) [3]
Description: Inhibition of AAK1 in a biochemical enzyme assay.
compound 13 [PMID: 34333981] Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.1 pIC50 2
pIC50 7.1 (IC50 7.4x10-8 M) [2]
compound 6 [PMID: 34333981] Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.1 pIC50 2
pIC50 7.1 (IC50 8x10-8 M) [2]
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: 1,7

Key to terms and symbols Click column headers to sort
Target used in screen: AAK1
Ligand Sp. Type Action Value Parameter
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 8.9 pKd
lestaurtinib Small molecule or natural product Immunopharmacology Ligand Hs Inhibitor Inhibition 8.5 pKd
sunitinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 8.0 pKd
fedratinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 7.5 pKd
A-674563 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 7.4 pKd
KW-2449 Small molecule or natural product Hs Inhibitor Inhibition 7.3 pKd
midostaurin Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 7.3 pKd
SU-14813 Small molecule or natural product Hs Inhibitor Inhibition 7.2 pKd
ruxolitinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 6.9 pKd
dovitinib Small molecule or natural product Hs Inhibitor Inhibition 6.8 pKd
Displaying the top 10 most potent ligands  View all ligands in screen »
Immuno Process Associations
Immuno Process:  Antigen presentation
GO Annotations:  Associated to 3 GO processes
GO:0030100 regulation of endocytosis IBA
GO:2000369 regulation of clathrin-dependent endocytosis IDA
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GO:0006897 endocytosis IEA
General Comments
Selective inhibition of AAK1 has validated it as a viable target for treating neuropathic pain [3]. It is also an antiviral drug target. Its inhibition by small molecules has the potential to offer promising broad-spectrum antiviral activity [6].

References

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1. 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]

2. Drewry DH, Annor-Gyamfi JK, Wells CI, Pickett JE, Dederer V, Preuss F, Mathea S, Axtman AD. (2022) Identification of Pyrimidine-Based Lead Compounds for Understudied Kinases Implicated in Driving Neurodegeneration. J Med Chem, 65 (2): 1313-1328. [PMID:34333981]

3. Hartz RA, Ahuja VT, Nara SJ, Kumar CMV, Brown JM, Bristow LJ, Rajamani R, Muckelbauer JK, Camac D, Kiefer SE et al.. (2021) Discovery, Structure-Activity Relationships, and In Vivo Evaluation of Novel Aryl Amides as Brain Penetrant Adaptor Protein 2-Associated Kinase 1 (AAK1) Inhibitors for the Treatment of Neuropathic Pain. J Med Chem, 64 (15): 11090-11128. [PMID:34270254]

4. Luo G, Chen L, Kostich WA, Hamman B, Allen J, Easton A, Bourin C, Gulianello M, Lippy J, Nara S et al.. (2022) Discovery and Optimization of Biaryl Alkyl Ethers as a Novel Class of Highly Selective, CNS-Penetrable, and Orally Active Adaptor Protein-2-Associated Kinase 1 (AAK1) Inhibitors for the Potential Treatment of Neuropathic Pain. J Med Chem, 65 (6): 4534-4564. [PMID:35261239]

5. Stebbing J, Phelan A, Griffin I, Tucker C, Oechsle O, Smith D, Richardson P. (2020) COVID-19: combining antiviral and anti-inflammatory treatments. Lancet Infect Dis, 20 (4): 400-402. [PMID:32113509]

6. Verdonck S, Pu SY, Sorrell FJ, Elkins JM, Froeyen M, Gao LJ, Prugar LI, Dorosky DE, Brannan JM, Barouch-Bentov R et al.. (2019) Synthesis and Structure-Activity Relationships of 3,5-Disubstituted-pyrrolo[2,3- b]pyridines as Inhibitors of Adaptor-Associated Kinase 1 with Antiviral Activity. J Med Chem, 62 (12): 5810-5831. [PMID:31136173]

7. 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

NAK family: AP2 associated kinase 1. Last modified on 29/03/2022. Accessed on 01/10/2022. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetomalariapharmacology.org/GRAC/ObjectDisplayForward?objectId=1921.