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unc-51 like autophagy activating kinase 1

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Target id: 2271

Nomenclature: unc-51 like autophagy activating kinase 1

Abbreviated Name: ULK1

Family: Unc-51-like kinase (ULK) family

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 1050 12q24.33 ULK1 unc-51 like autophagy activating kinase 1
Mouse - 1051 5 F Ulk1 unc-51 like kinase 1
Rat - 1051 12 q16 Ulk1 unc-51 like autophagy activating kinase 1
Previous and Unofficial Names Click here for help
ATG1 | ATG1A
Database Links Click here for help
Alphafold O75385 (Hs), O70405 (Mm)
BRENDA 2.7.11.1
ChEMBL Target CHEMBL6006 (Hs)
Ensembl Gene ENSG00000177169 (Hs), ENSMUSG00000029512 (Mm), ENSRNOG00000037505 (Rn)
Entrez Gene 8408 (Hs), 22241 (Mm), 360827 (Rn)
Human Protein Atlas ENSG00000177169 (Hs)
KEGG Enzyme 2.7.11.1
KEGG Gene hsa:8408 (Hs), mmu:22241 (Mm), rno:360827 (Rn)
OMIM 603168 (Hs)
Pharos O75385 (Hs)
RefSeq Nucleotide NM_003565 (Hs), NM_009469 (Mm), NM_001108341 (Rn)
RefSeq Protein NP_003556 (Hs), NP_033495 (Mm), NP_001101811 (Rn)
UniProtKB O75385 (Hs), O70405 (Mm)
Wikipedia ULK1 (Hs)
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
SBP-7455 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.9 pIC50 6
⤷ pIC50 7.9 (IC50 1.3x10-8 M) [6]
Description: Inhibition determined in a NanoBRET assay.
inlexisertib Small molecule or natural product Hs Inhibition 7.0 – 7.6 pIC50 4
⤷ pIC50 7.0 – 7.6 (IC50 1x10-7 – 2.5x10-8 M) [4]
SBI-0206965 Small molecule or natural product Ligand has a PDB structure Hs Inhibition 6.9 pIC50 3
⤷ pIC50 6.9 (IC50 1.3x10-7 M) [3]
compound R-16 [PMID: 21967808] Small molecule or natural product Click here for species-specific activity table Hs Inhibition - - 5
⤷ [5]
Description: Measured as % inhibition using 1μM compound.
Inhibitor Comments
ULK1 activity is inhibited by 99% in the presence of 1μM compound R-16 [PMID 21967808] [5].
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: 2,7
Key to terms and symbols Click column headers to sort
Target used in screen: ULK1
Ligand Sp. Type Action Value Parameter
NVP-TAE684 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 9.1 pKd
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 8.0 pKd
tamatinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 7.8 pKd
sunitinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 7.6 pKd
KW-2449 Small molecule or natural product Hs Inhibitor Inhibition 7.3 pKd
dovitinib Small molecule or natural product Hs Inhibitor Inhibition 7.3 pKd
SU-14813 Small molecule or natural product Hs Inhibitor Inhibition 7.1 pKd
fedratinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 6.6 pKd
ruxolitinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 6.5 pKd
crizotinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 6.0 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
Key to terms and symbols Click column headers to sort
Target used in screen: nd/ULK1
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 3.3
Cdk1/2 inhibitor III Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 5.0
SU11274 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 5.2
SU6656 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.1
JAK3 inhibitor VI Small molecule or natural product Hs Inhibitor Inhibition 11.5
JAK inhibitor I Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 12.8
SU11652 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 13.6
sunitinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 16.3
dovitinib Small molecule or natural product Hs Inhibitor Inhibition 20.4
PKR inhibitor Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 21.0
Displaying the top 10 most potent ligands  View all ligands in screen »
Immuno Process Associations
Immuno Process:  Antigen presentation

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. Egan DF, Chun MG, Vamos M, Zou H, Rong J, Miller CJ, Lou HJ, Raveendra-Panickar D, Yang CC, Sheffler DJ et al.. (2015) Small Molecule Inhibition of the Autophagy Kinase ULK1 and Identification of ULK1 Substrates. Mol Cell, 59 (2): 285-97. [PMID:26118643]

4. Flynn DL, Ahn YM, Calswell T, Vogeti L. (2022) Phenylaminopyrimidine amide autophagy inhibitors and methods of use thereof. Patent number: US11530206B2. Assignee: Deciphera Pharmaceuticals LLC. Priority date: 08/05/2020. Publication date: 20/12/2022.

5. Milkiewicz KL, Aimone LD, Albom MS, Angeles TS, Chang H, Grobelny JV, Husten J, Losardo C, Miknyoczki S, Murthy S et al.. (2011) Improvement in oral bioavailability of 2,4-diaminopyrimidine c-Met inhibitors by incorporation of a 3-amidobenzazepin-2-one group. Bioorg Med Chem, 19 (21): 6274-84. [PMID:21967808]

6. Ren H, Bakas NA, Vamos M, Chaikuad A, Limpert AS, Wimer CD, Brun SN, Lambert LJ, Tautz L, Celeridad M et al.. (2020) Design, Synthesis, and Characterization of an Orally Active Dual-Specific ULK1/2 Autophagy Inhibitor that Synergizes with the PARP Inhibitor Olaparib for the Treatment of Triple-Negative Breast Cancer. J Med Chem, 63 (23): 14609-14625. [PMID:33200929]

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

Unc-51-like kinase (ULK) family: unc-51 like autophagy activating kinase 1. Last modified on 05/03/2024. Accessed on 19/04/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetomalariapharmacology.org/GRAC/ObjectDisplayForward?objectId=2271.