General Information of the Protein
Protein ID
PT02366
Protein Name
Serine/threonine-protein kinase ULK1
Secondarily
Protein Name
Autophagy-related protein 1 homolog
Unc-51-like kinase 1
Gene Name
ULK1
Secondarily
Gene Name
KIAA0722
Sequence
MEPGRGGTETVGKFEFSRKDLIGHGAFAVVFKGRHREKHDLEVAVKCINKKNLAKSQTLLGKEIKILKELKHENIVALYDFQEMANSVYLVMEYCNGGDLADYLHAMRTLSEDTIRLFLQQIAGAMRLLHSKGIIHRDLKPQNILLSNPAGRRANPNSIRVKIADFGFARYLQSNMMAATLCGSPMYMAPEVIMSQHYDGKADLWSIGTIVYQCLTGKAPFQASSPQDLRLFYEKNKTLVPTIPRETSAPLRQLLLALLQRNHKDRMDFDEFFHHPFLDASPSVRKSPPVPVPSYPSSGSGSSSSSSSTSHLASPPSLGEMQQLQKTLASPADTAGFLHSSRDSGGSKDSSCDTDDFVMVPAQFPGDLVAEAPSAKPPPDSLMCSGSSLVASAGLESHGRTPSPSPPCSSSPSPSGRAGPFSSSRCGASVPIPVPTQVQNYQRIERNLQSPTQFQTPRSSAIRRSGSTSPLGFARASPSPPAHAEHGGVLARKMSLGGGRPYTPSPQVGTIPERPGWSGTPSPQGAEMRGGRSPRPGSSAPEHSPRTSGLGCRLHSAPNLSDLHVVRPKLPKPPTDPLGAVFSPPQASPPQPSHGLQSCRNLRGSPKLPDFLQRNPLPPILGSPTKAVPSFDFPKTPSSQNLLALLARQGVVMTPPRNRTLPDLSEVGPFHGQPLGPGLRPGEDPKGPFGRSFSTSRLTDLLLKAAFGTQAPDPGSTESLQEKPMEIAPSAGFGGSLHPGARAGGTSSPSPVVFTVGSPPSGSTPPQGPRTRMFSAGPTGSASSSARHLVPGPCSEAPAPELPAPGHGCSFADPITANLEGAVTFEAPDLPEETLMEQEHTEILRGLRFTLLFVQHVLEIAALKGSASEAAGGPEYQLQESVVADQISLLSREWGFAEQLVLYLKVAELLSSGLQSAIDQIRAGKLCLSSTVKQVVRRLNELYKASVVSCQGLSLRLQRFFLDKQRLLDRIHSITAERLIFSHAVQMVQSAALDEMFQHREGCVPRYHKALLLLEGLQHMLSDQADIENVTKCKLCIERRLSALLTGICA
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Organism
Homo sapiens, Human
Protein Classification
Enzyme
>
Kinase
>
Protein Kinase
>
Other protein kinase group
>
Other protein kinase ULK family
Function
Serine/threonine-protein kinase involved in autophagy in response to starvation (PubMed:18936157, PubMed:21460634, PubMed:21795849, PubMed:23524951, PubMed:25040165, PubMed:31123703, PubMed:29487085). Acts upstream of phosphatidylinositol 3-kinase PIK3C3 to regulate the formation of autophagophores, the precursors of autophagosomes (PubMed:18936157, PubMed:21460634, PubMed:21795849, PubMed:25040165). Part of regulatory feedback loops in autophagy: acts both as a downstream effector and negative regulator of mammalian target of rapamycin complex 1 (mTORC1) via interaction with RPTOR (PubMed:21795849). Activated via phosphorylation by AMPK and also acts as a regulator of AMPK by mediating phosphorylation of AMPK subunits PRKAA1, PRKAB2 and PRKAG1, leading to negatively regulate AMPK activity (PubMed:21460634). May phosphorylate ATG13/KIAA0652 and RPTOR; however such data need additional evidences (PubMed:18936157). Plays a role early in neuronal differentiation and is required for granule cell axon formation (PubMed:11146101). May also phosphorylate SESN2 and SQSTM1 to regulate autophagy (PubMed:25040165). Phosphorylates FLCN, promoting autophagy (PubMed:25126726). Phosphorylates AMBRA1 in response to autophagy induction, releasing AMBRA1 from the cytoskeletal docking site to induce autophagosome nucleation (PubMed:20921139). Phosphorylates ATG4B, leading to inhibit autophagy by decreasing both proteolytic activation and delipidation activities of ATG4B (PubMed:28821708).
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Uniprot ID
Primary ID:
O75385

Secondarily ID:
Q9UQ28
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HGNC ID
HGNC:12558
Subcellular Location
Cytoplasm
Cytosol
Preautophagosomal structure
Map of Molecular Bioactivity Related to the Protein
Map of Molecular Bioactivity Related to the Protein

Protein
Cell Line
Compound

Bioactivity Value:

<= 0.1 μM
> 0.1 μM and <= 10 μM
> 10 μM
Imprecise Activity
Table of Molecular Bioactivities Related to the Protein
Cell Line ID: CL000025 , HEK-293T
Compound ID Compound Name Compound Formula
CP0073242
3-amino-N-[3-(naphthalen-1-ylamino)-1H-indazol-5-yl]cyclohexane-1-carboxamide
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C24H25N5O
 1
1
IC50 = 11 nM
   TI
   LI
   LO
   TS
CP0393126
(1R,3R)-3-amino-N-[3-(naphthalen-1-ylamino)-1H-indazol-5-yl]cyclohexane-1-carboxamide
   Show/Hide
C24H25N5O
 1
1
IC50 = 24 nM
   TI
   LI
   LO
   TS
CP0555861
3-amino-N-[3-(quinolin-5-ylamino)-1H-indazol-5-yl]cyclohexane-1-carboxamide
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C23H24N6O
 1
1
IC50 = 40 nM
   TI
   LI
   LO
   TS
CP0180547
(1R,3S)-3-amino-N-[3-(naphthalen-1-ylamino)-1H-indazol-5-yl]cyclohexane-1-carboxamide
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C24H25N5O
 1
1
IC50 = 45 nM
   TI
   LI
   LO
   TS
CP0073246
3-amino-N-[3-(2-methoxyanilino)-1H-indazol-5-yl]cyclohexane-1-carboxamide
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C21H25N5O2
 1
1
IC50 = 110 nM
   TI
   LI
   LO
   TS
CP0393124
methyl 3-[[5-[(3-aminocyclohexanecarbonyl)amino]-1H-indazol-3-yl]amino]benzoate
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C22H25N5O3
 1
1
IC50 = 183 nM
   TI
   LI
   LO
   TS
CP0476222
3-amino-N-[3-(quinolin-4-ylamino)-1H-indazol-5-yl]cyclohexane-1-carboxamide
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C23H24N6O
 1
1
IC50 = 239 nM
   TI
   LI
   LO
   TS
CP0486132
N-[5-[(3-aminocyclohexanecarbonyl)amino]-1H-indazol-3-yl]benzamide
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C21H23N5O2
 1
1
IC50 = 242 nM
   TI
   LI
   LO
   TS
CP0519753
3-amino-N-[3-[3-(trifluoromethyl)anilino]-1H-indazol-5-yl]cyclohexane-1-carboxamide
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C21H22F3N5O
 1
1
IC50 = 288 nM
   TI
   LI
   LO
   TS
CP0073243
N-[3-(naphthalen-1-ylamino)-1H-indazol-5-yl]piperidine-4-carboxamide
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C23H23N5O
 1
1
IC50 = 315 nM
   TI
   LI
   LO
   TS
CP0489042
US10266549, Example 349
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C16H17F3N4O2
 1
1
IC50 = 328 nM
   TI
   LI
   LO
   TS
CP0389618
(1S,3R)-3-amino-N-(3-amino-1H-indazol-5-yl)cyclohexane-1-carboxamide
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C14H19N5O
 1
1
IC50 = 330 nM
   TI
   LI
   LO
   TS
CP0486134
3-amino-N-(3-amino-1H-indazol-5-yl)cyclohexane-1-carboxamide
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C14H19N5O
 1
1
IC50 = 368 nM
   TI
   LI
   LO
   TS
CP0482635
3-amino-N-[3-(4-bromoanilino)-1H-indazol-5-yl]cyclohexane-1-carboxamide
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C20H22BrN5O
 1
1
IC50 = 416 nM
   TI
   LI
   LO
   TS
CP0478300
3-amino-N-[3-[(4-methoxyphenyl)methylamino]-1H-indazol-5-yl]cyclohexane-1-carboxamide
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C22H27N5O2
 1
1
IC50 = 477 nM
   TI
   LI
   LO
   TS
CP0930412
N-(3-amino-1H-indazol-5-yl)piperidine-4-carboxamide
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C13H17N5O
 1
1
IC50 = 560 nM
   TI
   LI
   LO
   TS
CP0495717
N4-cyclopropyl-N2-(5-methoxypyridin-3-yl)-5-(trifluoromethyl) pyrimidine-2,4-diamine
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C14H14F3N5O
 1
1
IC50 = 582 nM
   TI
   LI
   LO
   TS
CP0515043
N2-(1H-benzo[d]imidazol-6-yl)-N4-cyclopropyl-5-(trifluoromethyl)pyrimidine-2,4-diamine
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C15H13F3N6
 1
1
IC50 = 585 nM
   TI
   LI
   LO
   TS
CP0486160
3-amino-N-[3-(quinolin-8-ylamino)-1H-indazol-5-yl]cyclohexane-1-carboxamide
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C23H24N6O
 1
1
IC50 = 589 nM
   TI
   LI
   LO
   TS
CP0393122
N-(3-amino-1H-indazol-5-yl)piperidine-3-carboxamide
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C13H17N5O
 1
1
IC50 = 670 nM
   TI
   LI
   LO
   TS
CP0540134
US10266549, Example 304a
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C14H14F3N5
 1
1
IC50 = 679 nM
   TI
   LI
   LO
   TS
CP0515037
N4-cyclopropyl-N2-(quinolin-6-yl)-5-(trifluoromethyl) pyrimidine-2,4-diamine
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C17H14F3N5
 1
1
IC50 = 739 nM
   TI
   LI
   LO
   TS
CP0331654
2-(5-Bromo-2-(3,4,5-trimethoxyphenylamino)pyrimidin-4-yloxy)-N-methylbenzamide
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C21H21BrN4O5
 1
1
IC50 = 785 nM
   TI
   LI
   LO
   TS
CP0389619
3-amino-N-[3-(2-fluoroanilino)-1H-indazol-5-yl]cyclohexane-1-carboxamide
   Show/Hide
C20H22FN5O
 1
1
IC50 = 840 nM
   TI
   LI
   LO
   TS
CP0960352
N-(3-amino-1H-indazol-5-yl)piperidine-2-carboxamide
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C13H17N5O
 1
1
IC50 = 840 nM
   TI
   LI
   LO
   TS
CP0537630
US10266549, Example 208a
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C15H12F3N5O
 1
1
IC50 = 1021 nM
   TI
   LI
   LO
   TS
CP0555696
N2-(1H-benzo[d][1,2,3]triazol-6-yl)-N4-cyclopropyl-5-(trifluoromethyl)pyrimidine-2,4-diamine
   Show/Hide
C14H12F3N7
 1
1
IC50 = 1168 nM
   TI
   LI
   LO
   TS
CP0535131
N4-cyclopropyl-N2-(4-ethyl-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-7-yl)-5-(trifluoromethyl)pyrimidine-2,4-diamine
   Show/Hide
C17H19F3N6O
 1
1
IC50 = 1215 nM
   TI
   LI
   LO
   TS
CP0558779
N-(4-((4-(cyclopropylamino)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)cyclopropanecarboxamide
   Show/Hide
C18H18F3N5O
 1
1
IC50 = 1327 nM
   TI
   LI
   LO
   TS
CP0560870
6-((4-(cyclopropylamino)-5-(trifluoromethyl)pyrimidin-2-yl)amino)-3,4-dihydronaphthalen-1(2H)-one
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C18H17F3N4O
 1
1
IC50 = 1361 nM
   TI
   LI
   LO
   TS
CP0535130
N4-cyclopropyl-N2-(quinoxalin-6-yl)-5-(trifluoromethyl) pyrimidine-2,4-diamine
   Show/Hide
C16H13F3N6
 1
1
IC50 = 1464 nM
   TI
   LI
   LO
   TS
CP0558848
N4-cyclopropyl-N2-(1H-indazol-5-yl)-5-(trifluoromethyl) pyrimidine-2,4-diamine
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C15H13F3N6
 1
1
IC50 = 1477 nM
   TI
   LI
   LO
   TS
CP0486133
4-amino-N-(3-amino-1H-indazol-5-yl)cyclohexane-1-carboxamide
   Show/Hide
C14H19N5O
 1
1
IC50 = 1490 nM
   TI
   LI
   LO
   TS
CP0576718
N4-cyclopropyl-N2-(3,4-dihydro-2H-benzo[b][1,4]dioxepin-7-yl)-5-(trifluoromethyl)pyrimidine-2,4-diamine
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C17H17F3N4O2
 1
1
IC50 = 1602 nM
   TI
   LI
   LO
   TS
CP0489044
US10266549, Example 221a
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C12H11F3N6
 1
1
IC50 = 1611 nM
   TI
   LI
   LO
   TS
CP0540140
N-(cyclopropanecarbonyl)-N-(4-((4-(cyclopropylamino)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)cyclopropanecarboxamide
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C22H22F3N5O2
 1
1
IC50 = 1713 nM
   TI
   LI
   LO
   TS
CP0446858
N-[3-(naphthalen-1-ylamino)-1H-indazol-5-yl]oxane-4-carboxamide
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C23H22N4O2
 1
1
IC50 = 1830 nM
   TI
   LI
   LO
   TS
CP0515038
US10266549, Example 152a
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C15H13F3N6
 1
1
IC50 = 1926 nM
   TI
   LI
   LO
   TS
CP0561719
3-hydroxy-N-[3-(naphthalen-1-ylamino)-1H-indazol-5-yl]cyclohexane-1-carboxamide
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C24H24N4O2
 1
1
IC50 = 2220 nM
   TI
   LI
   LO
   TS
CP0478301
3-amino-N-(3-anilino-1H-indazol-5-yl)cyclohexane-1-carboxamide
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C20H23N5O
 1
1
IC50 = 2730 nM
   TI
   LI
   LO
   TS
CP0393125
(1S,3R)-3-amino-N-[3-(naphthalen-1-ylamino)-1H-indazol-5-yl]cyclohexane-1-carboxamide
   Show/Hide
C24H25N5O
 1
1
IC50 = 3050 nM
   TI
   LI
   LO
   TS
CP0569808
US10266549, Example 182a
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C13H11F3N6
 1
1
IC50 = 3631 nM
   TI
   LI
   LO
   TS
CP0486162
3-(dimethylamino)-N-[3-(naphthalen-1-ylamino)-1H-indazol-5-yl]cyclohexane-1-carboxamide
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C26H29N5O
 1
1
IC50 = 4230 nM
   TI
   LI
   LO
   TS
CP0515040
US10266549, Example 158a
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C16H15F3N4O2
 1
1
IC50 = 4475 nM
   TI
   LI
   LO
   TS
CP0478303
N-[3-(naphthalen-1-ylamino)-1H-indazol-5-yl]azetidine-3-carboxamide
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C21H19N5O
 1
1
IC50 = 4940 nM
   TI
   LI
   LO
   TS
CP0515041
2-((4-(cyclopropylamino)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenol
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C14H13F3N4O
 1
1
IC50 = 6038 nM
   TI
   LI
   LO
   TS
CP0560871
N4-cyclopropyl-N2-(1H-indol-5-yl)-5-(trifluoromethyl) pyrimidine-2,4-diamine
   Show/Hide
C16H14F3N5
 1
1
IC50 = 9838 nM
   TI
   LI
   LO
   TS
CP0495718
US10266549, Example 161a
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C16H15F3N6
 1
1
IC50 > 10000 nM
   TI
   LI
   LO
   TS
CP0515042
N4-cyclopropyl-N2-(quinolin-3-yl)-5-(trifluoromethyl) pyrimidine-2,4-diamine
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C17H14F3N5
 1
1
IC50 > 10000 nM
   TI
   LI
   LO
   TS
CP0553085
N2-(benzo[d][1,3]dioxol-5-yl)-N4-cyclopropyl-5-(trifluoromethyl)pyrimidine-2,4-diamine
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C15H13F3N4O2
 1
1
IC50 > 10000 nM
   TI
   LI
   LO
   TS
CP0555697
N4-cyclopropyl-N2-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)-5-(trifluoromethyl)pyrimidine-2,4-diamine
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C15H11F5N4O2
 1
1
IC50 > 10000 nM
   TI
   LI
   LO
   TS
CP0569864
US10266549, Example 165b
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C12H9F3N4O2
 1
1
IC50 > 10000 nM
   TI
   LI
   LO
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CP0567008
4-amino-N-(3-amino-1H-indazol-5-yl)cyclohexane-1-carboxamide
   Show/Hide
C14H19N5O
 1
1
IC50 = 13960 nM
   TI
   LI
   LO
   TS
CP0482634
3-amino-N-(3-amino-1H-indazol-5-yl)benzamide
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C14H13N5O
 1
1
IC50 = 18100 nM
   TI
   LI
   LO
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CP0393123
3-amino-N-(1H-indazol-5-yl)cyclohexane-1-carboxamide
   Show/Hide
C14H18N4O
 1
1
IC50 = 22400 nM
   TI
   LI
   LO
   TS
CP0560459
4-amino-N-(3-amino-1H-indazol-5-yl)butanamide
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C11H15N5O
 1
1
IC50 > 33000 nM
   TI
   LI
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Biochemical Assays
Compound ID Compound Name Compound Formula
CP0231485
2-[bis(2-methylpropyl)amino]-1-[4-[2-(2,4-dichlorophenyl)-2-(naphthalen-2-ylmethoxy)ethyl]piperazin-1-yl]ethanone
   Show/Hide
C33H43Cl2N3O2
 1
1 EC50 = 18.94 nM
CP0331654
2-(5-Bromo-2-(3,4,5-trimethoxyphenylamino)pyrimidin-4-yloxy)-N-methylbenzamide
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C21H21BrN4O5
 1
1 IC50 = 108 nM
CP0014270
(2R)-2-[[3,5-bis(trifluoromethyl)phenyl]carbamothioylamino]-N-(2,5-difluorophenyl)-2-phenylacetamide
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C23H15F8N3OS
 1
1 Kd = 719 nM
Clinical Information about the Protein
Target 1 ( Serine/threonine-protein kinase ULK1 (ULK1) )
Target Type Literature-reported Target