ULK1

Summary

ULK1 (unc-51 like autophagy activating kinase 1, HGNC:12558) is a protein-coding gene on chromosome 12q24.33, encoding Serine/threonine-protein kinase ULK1 (O75385). Serine/threonine-protein kinase involved in autophagy in response to starvation.

Enables identical protein binding activity; protein serine/threonine kinase activity; and small GTPase binding activity. Involved in several processes, including autophagosome assembly; protein phosphorylation; and regulation of autophagy. Located in bounding membrane of organelle; cytosol; and phagophore assembly site membrane. Part of Atg1/ULK1 kinase complex. Is active in cytoplasm.

Source: NCBI Gene 8408 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 240 total
• Druggable target: yes — 24 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_003565

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12558
Approved symbol	ULK1
Name	unc-51 like autophagy activating kinase 1
Location	12q24.33
Locus type	gene with protein product
Status	Approved
Aliases	ATG1, ATG1A
Ensembl gene	ENSG00000177169
Ensembl biotype	protein_coding
OMIM	603168
Entrez	8408

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 6 retained_intron, 4 protein_coding

ENST00000321867, ENST00000537421, ENST00000540568, ENST00000540647, ENST00000541761, ENST00000542313, ENST00000544718, ENST00000881565, ENST00000939866, ENST00000939867

RefSeq mRNA: 1 — MANE Select: NM_003565 NM_003565

CCDS: CCDS9274

Canonical transcript exons

ENST00000321867 — 28 exons

Exon	Start	End
ENSE00001223524	131916398	131916591
ENSE00001223530	131915891	131916159
ENSE00001223543	131915083	131915231
ENSE00001223551	131914352	131914477
ENSE00001223559	131913747	131913836
ENSE00001223564	131913198	131913258
ENSE00001223571	131911942	131912089
ENSE00001223580	131910712	131910800
ENSE00001223587	131910254	131910304
ENSE00001223596	131909919	131910001
ENSE00001223646	131906892	131906924
ENSE00001223654	131895783	131895824
ENSE00001223668	131895601	131895693
ENSE00001315458	131921306	131923150
ENSE00001325150	131894622	131895112
ENSE00003469346	131921100	131921235
ENSE00003472428	131915335	131915421
ENSE00003716261	131908644	131908817
ENSE00003717541	131908898	131908971
ENSE00003720024	131909775	131909833
ENSE00003724310	131919212	131919384
ENSE00003724540	131919979	131920136
ENSE00003724553	131918497	131918681
ENSE00003729815	131909136	131909237
ENSE00003732346	131907495	131907531
ENSE00003735032	131916953	131917062
ENSE00003742584	131917411	131917554
ENSE00003746254	131919472	131919590

Expression profiles

Bgee: expression breadth ubiquitous, 234 present calls, max score 96.07.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 30.8057 / max 1442.8566, expressed in 1807 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
128766	20.9464	1800
128767	6.9052	1582
128768	1.3480	648
128765	1.3374	773
206961	0.2687	130

Top tissues by expression

274 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
body of pancreas	UBERON:0001150	96.07	gold quality
left ovary	UBERON:0002119	95.53	gold quality
right hemisphere of cerebellum	UBERON:0014890	95.45	gold quality
gastrocnemius	UBERON:0001388	95.37	gold quality
skin of leg	UBERON:0001511	95.19	gold quality
adenohypophysis	UBERON:0002196	95.05	gold quality
mucosa of stomach	UBERON:0001199	94.95	gold quality
right ovary	UBERON:0002118	94.83	gold quality
cerebellar hemisphere	UBERON:0002245	94.70	gold quality
middle frontal gyrus	UBERON:0002702	94.65	gold quality
cerebellar cortex	UBERON:0002129	94.63	gold quality
pituitary gland	UBERON:0000007	94.61	gold quality
nucleus accumbens	UBERON:0001882	94.52	gold quality
apex of heart	UBERON:0002098	94.42	gold quality
skin of abdomen	UBERON:0001416	94.20	gold quality
endocervix	UBERON:0000458	93.81	gold quality
ectocervix	UBERON:0012249	93.66	gold quality
muscle of leg	UBERON:0001383	93.64	gold quality
hindlimb stylopod muscle	UBERON:0004252	93.51	gold quality
cerebellum	UBERON:0002037	93.47	gold quality
right adrenal gland cortex	UBERON:0035827	93.47	gold quality
lower esophagus muscularis layer	UBERON:0035833	93.45	gold quality
lower esophagus	UBERON:0013473	93.44	gold quality
lower esophagus mucosa	UBERON:0035834	93.44	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	93.28	gold quality
body of uterus	UBERON:0009853	93.24	gold quality
right adrenal gland	UBERON:0001233	93.07	gold quality
right uterine tube	UBERON:0001302	93.04	gold quality
muscle layer of sigmoid colon	UBERON:0035805	92.95	gold quality
body of stomach	UBERON:0001161	92.86	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.25

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
ATG13	Unknown

Upstream regulators (CollecTRI, top): E2F1, SMCR8, SSRP1

miRNA regulators (miRDB)

132 targeting ULK1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-4650-5P	99.98	64.69	999
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-4778-3P	99.93	70.40	1818
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-1297	99.91	73.41	3162

Literature-anchored findings (GeneRIF, showing 40)

• Starvation-induced autophagy, which requires mAtg9, may rely on an alteration of the steady-state trafficking of mAtg9, in a Atg1-dependent manner. (PMID:16940348)
• ULK1 knockdown inhibited rapamycin-induced autophagy consistent with a role downstream of mTOR (PMID:17595159)
• The functions of ULK1 and ULK2 are controlled by autophosphorylation and conformational changes involving exposure of the C-terminal domain and interaction with the putative human homologue of Atg13. (PMID:18936157)
• mTORC1 suppresses autophagy through direct regulation of the approximately 3-MDa ULK1-Atg13-FIP200 complex. (PMID:19211835)
• The ULK-Atg13-FIP200 complexes are direct targets of mTOR and important regulators of autophagy in response to mTOR signaling. (PMID:19225151)
• ATG13 and ULK1 are phosphorylated by the mTOR pathway in a nutrient starvation-regulated manner, indicating that the ULK1.ATG13.FIP200 complex acts as a node for integrating incoming autophagy signals into autophagosome biogenesis. (PMID:19258318)
• The identification of the novel protein, Atg101, and the validation of Atg13 and Atg101 as ULK1-interacting proteins, suggests an Atg1 complex is involved in the induction of macroautophagy in mammalian cells. (PMID:19287211)
• Studies elucidated the inhibitory mechanism in which mTORC1 phosphorylates the autophagy regulatory complex containing unc-51-like kinase 1 (ULK1), the mammalian Atg13 protein, and focal adhesion kinase interacting protein of 200 kD (FIP200). (PMID:19690328)
• Results suggest that AMPK association with ULK1 plays an important role in autophagy induction. (PMID:21072212)
• findings uncover a conserved mechanism coupling nutrient status with autophagy and cell survival; loss of AMPK or ULK1 result in defective mitophagy;phosphorylation of ULK1 by AMPK required for mitochondrial homeostasis and cell survival during starvation (PMID:21205641)
• Data show that under nutrient sufficiency, high mTOR activity prevents Ulk1 activation by phosphorylating Ulk1 Ser 757 and disrupting the interaction between Ulk1 and AMPK. (PMID:21258367)
• ULK1 contributes to mTORC1 inhibition through hindrance of substrate docking to Raptor. (PMID:21460630)
• Phosphorylation of AMPK by Ulk1 represents a negative feedback circuit. (PMID:21460634)
• In response to DNA damage, ULK1 and ULK2 are upregulated by p53. The upregulation of ULK1 (ULK2)/ATG13 complex by p53 is necessary for the sustained autophagy activity induced by DNA damage. (PMID:21475306)
• ULK1 represents a novel and clinically useful biomarker for esophageal squamous cell carcinoma (ESCC) patients and plays an important role during the progression of ESCC. (PMID:21518141)
• study found frequency of the T-allele of tSNP rs12303764 in ULK1 was significantly higher in Crohn’s disease versus contrtols (PMID:21560199)
• ULK1 negatively regulates the kinase activity of mTORC1 and cell proliferation in a manner independent of Atg5 and TSC2 (PMID:21795849)
• our results suggest that ULK1 may act as a major node for regulation by multiple kinases including AMPK and Akt that play both stimulatory and inhibitory roles in regulating autophagy. (PMID:21819378)
• glycogen synthase kinase-3 (GSK3), when deinhibited by default in cells deprived of growth factors, activates acetyltransferase TIP60 through phosphorylating TIP60-Ser86, which acetylates and stimulates the protein kinase ULK1, which is required for autophagy (PMID:22539723)
• Decreased expression of ULK1 is associated with breast cancer progression, together with closely related to decreased autophagic capacity. (PMID:22585231)
• The ULK1 and Atg9 are found on Rab11- and transferrin (Tfn) receptor (TfnR)-positive recycling endosomes. (PMID:22613832)
• Binding of the Atg1/ULK1 kinase to the ubiquitin-like protein Atg8 regulates autophagy (PMID:22885598)
• amino acid starvation regulates autophagy in part through an increase in cellular Ca(2+) that activates a CaMKK-beta-AMPK pathway and inhibits mTORC1, which results in ULK1 stimulation (PMID:23027865)
• Data show that the autophagy-initiating kinase ULK1 (UNC51-like kinase 1) is a direct transcriptional target of ATF4 (activating transcription factor 4), which drives the expression of ULK1 mRNA and protein in severe hypoxia and ER stress. (PMID:23078367)
• ULK1-dependent autophagy degrades BNIP3 via MTORC1 and AMPK (PMID:23291726)
• proposed that mTOR, besides its negative regulation of ULK1 through its direct phosphorylation, may also indirectly inhibit ULK1 stability and activity by modifying AMBRA1 and impairing its E3-ligase-related functions (PMID:23524951)
• Findings show that Ypt1/Rab1 infindings show that Ypt1/Rab1 interacts with Atg1/Ulk1 in yeast and mammalian cells. (PMID:23716696)
• ULK1 is a hypoxia regulated gene and is associated with hypoxia tolerance and a worse clinical outcome. (PMID:23849170)
• In order for cells to control cellular homoeostasis during growth, there is close signalling interplay between mTORC1 and two other protein kinases, AMPK and ULK1 (PMID:23863160)
• ULK1 complex forms puncta associated with the ER and sporadically with mitochondria (PMID:24013547)
• ULK1 regulates melanin levels in MNT-1 cells independently of mTORC1. (PMID:24066173)
• After activation and trafficking, STING is phosphorylated by UNC-51-like kinase (ULK1). This occurs following ULK1 dissociation from its repressor AMPK and was found to be triggered by cGAS-generated cyclic dinucleotides. (PMID:24119841)
• Single nucleotide polymorphism in ATG1 gene is associated with Hodgkin disease therapy induced second malignancy. (PMID:24306881)
• FUNDC1 regulates ULK1 recruitment to damaged mitochondria, where FUNDC1 phosphorylation by ULK1 is crucial for mitophagy. (PMID:24671035)
• silencing of EEF2K promotes autophagic survival via activation of the AMPK-ULK1 pathway in colon cancer cells (PMID:24955726)
• The FLCN-GABARAP association is modulated by the presence of either folliculin-interacting protein (FNIP)-1 or FNIP2 and further regulated by ULK1. (PMID:25126726)
• Data show that under basal and stressed conditions, AMPK and ULK1 are differentially required for Atg2A S761 phosphorylation. (PMID:25266655)
• Reactive oxygen species inhibited autophagy by downregulating the p70S6K/p53/ULK1 axis in selenite-treated NB4 cells. (PMID:25429619)
• The results show that nitric oxide stabilizes SIRT1 by regulating 26S proteasome functionality through ULK1 and O-linked-GlcNAc transferase, but not autophagy, in endothelial cells. (PMID:25541949)
• Physical exercise increased phosphorylation at Ser(555); phosphorylation at Ser(757) was not affected by exercise. (PMID:25678702)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	ulk1b	ENSDARG00000074481
mus_musculus	Ulk1	ENSMUSG00000029512
rattus_norvegicus	Ulk1	ENSRNOG00000037505
drosophila_melanogaster	Atg1	FBGN0260945
caenorhabditis_elegans		WBGENE00006786

Paralogs (2): ULK2 (ENSG00000083290), ULK3 (ENSG00000140474)

Protein

Protein identifiers

Serine/threonine-protein kinase ULK1 — O75385 (reviewed: O75385)

Alternative names: Autophagy-related protein 1 homolog, Unc-51-like kinase 1

All UniProt accessions (1): O75385

UniProt curated annotations — full annotation on UniProt →

Function. Serine/threonine-protein kinase involved in autophagy in response to starvation. Acts upstream of phosphatidylinositol 3-kinase PIK3C3 to regulate the formation of autophagophores, the precursors of autophagosomes. 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. 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. May phosphorylate ATG13/KIAA0652 and RPTOR; however such data need additional evidences. Plays a role early in neuronal differentiation and is required for granule cell axon formation. Also phosphorylates SESN2 and SQSTM1 to regulate autophagy. Phosphorylates FLCN, promoting autophagy. Phosphorylates AMBRA1 in response to autophagy induction, releasing AMBRA1 from the cytoskeletal docking site to induce autophagosome nucleation. Phosphorylates ATG4B, leading to inhibit autophagy by decreasing both proteolytic activation and delipidation activities of ATG4B.

Subunit / interactions. Interacts with GABARAP and GABARAPL2. Interacts (via C-terminus) with ATG13. Part of a complex consisting of ATG13, ATG101, ULK1 and RB1CC1. Associates with the mammalian target of rapamycin complex 1 (mTORC1) through an interaction with RPTOR; the association depends on nutrient conditions and is reduced during starvation. Interacts with FEZ1; SCOC interferes with FEZ1-binding. Interacts with TBC1D14. Interacts (phosphorylated form) with TRIM5. When phosphorylated at Ser-317, interacts with MEFV and BECN1 simultaneously. Interacts with TRIM21 and IRF3, in the presence of TRIM21. Interacts with SESN2. Interacts with SQSTM1. Interacts with C9orf72. Interacts with WDR45. Interacts with ATG13; this interaction is increased in the absence of TMEM39A. Interacts with WIPI2. Interacts with ATP2A2. Interacts with AMBRA1. Interacts with IRGM; promoting the coassembly of ULK1 and BECN1. Interacts with FBXO16.

Subcellular location. Cytoplasm. Cytosol. Preautophagosomal structure.

Tissue specificity. Ubiquitously expressed. Detected in the following adult tissues: skeletal muscle, heart, pancreas, brain, placenta, liver, kidney, and lung.

Post-translational modifications. Autophosphorylated. Phosphorylated under nutrient-rich conditions; dephosphorylated during starvation or following treatment with rapamycin. Under nutrient sufficiency, phosphorylated by MTOR/mTOR, disrupting the interaction with AMPK and preventing activation of ULK1. In response to nutrient limitation, phosphorylated and activated by AMPK, leading to activate autophagy. Ubiquitinated via ‘Lys-63’-linkage by a complex composed of AMBRA1 and TRAF6 following autophagy induction, promoting ULK1 stability and kinase activity. Deubiquitinated by USP20; leading to ULK1 stability and autophagy initiation. Ubiquitinated by the SCF-FBXO16 E3 ubiquitin ligase, leading to proteasomal degradation. Acetylated by KAT5/TIP60 under autophagy induction, promoting protein kinase activity.

Activity regulation. Acetylation by KAT5/TIP60 stimulates the protein kinase activity. The protein kinase activity is activated by unanchored ‘Lys-63’-linked polyubiquitin chains: unanchored ‘Lys-63’-linked polyubiquitin chains are catalyzed by TRIM32 in an AMBRA1-dependent manner.

Similarity. Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. APG1/unc-51/ULK1 subfamily.

RefSeq proteins (1): NP_003556* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000719	Prot_kinase_dom	Domain
IPR008271	Ser/Thr_kinase_AS	Active_site
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR016237	Ser/Thr_kin_STPK_Ulk-1/2	Family
IPR017441	Protein_kinase_ATP_BS	Binding_site
IPR022708	Atg1-like_tMIT	Domain
IPR045269	Atg1-like	Family
IPR048941	ATG1-like_MIT2	Domain

Pfam: PF00069, PF12063, PF21127

Enzyme classification (BRENDA):

• EC 2.7.11.1 — non-specific serine/threonine protein kinase (BRENDA: 71 organisms, 682 substrates, 228 inhibitors, 23 Km, 6 kcat entries)

Substrate kinetics (BRENDA)

8 substrates with measured Km, best-characterized 8. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ATP	0.0007–0.64	11
KKRAARATSNVFA	0.013–0.045	3
PAH1 PHOSPHATIDATE PHOSPHATASE	0.0002	2
RRRLSSLRA	0.0036–0.0037	2
GTP	0.46	1
KKRAARASSNVFA	0.02	1
LYS-LYS-PHE-ASN-ARG-THR-LEU-SER-VAL-ALA	0.0093	1
MYELIN BASIC PROTEIN	0.145	1

Catalyzed reactions (Rhea), 2 shown:

• L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H(+) (RHEA:17989)
• L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H(+) (RHEA:46608)

UniProt features (65 total): modified residue 18, helix 13, strand 9, sequence variant 8, region of interest 5, compositionally biased region 4, binding site 2, turn 2, chain 1, domain 1, active site 1, mutagenesis site 1

Structure

Experimental structures (PDB)

18 structures.

PDB	Method	Resolution (Å)
6HYO	X-RAY DIFFRACTION	1.07
4WNO	X-RAY DIFFRACTION	1.56
6MNH	X-RAY DIFFRACTION	1.73
5CI7	X-RAY DIFFRACTION	1.74
6QAS	X-RAY DIFFRACTION	1.75
8P5I	X-RAY DIFFRACTION	1.83
8P5L	X-RAY DIFFRACTION	1.84
4WNP	X-RAY DIFFRACTION	1.88
8P5H	X-RAY DIFFRACTION	1.94
8P5G	X-RAY DIFFRACTION	2.02
9F32	X-RAY DIFFRACTION	2.1
8P5J	X-RAY DIFFRACTION	2.16
8P5K	X-RAY DIFFRACTION	2.21
8SV9	X-RAY DIFFRACTION	2.3
8SOI	ELECTRON MICROSCOPY	4.2
8SRM	ELECTRON MICROSCOPY	4.46
8SQZ	ELECTRON MICROSCOPY	5.85
9C82	ELECTRON MICROSCOPY	6.84

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O75385-F1	60.99	0.30

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1): 138 (proton acceptor)

Ligand- & substrate-binding residues (2): 22–30; 46

Post-translational modifications (18): 162, 317, 403, 450, 456, 467, 469, 477, 479, 522, 556, 575, 607, 636, 638, 639, 758, 775

Mutagenesis-validated functional residues (1):

Position	Phenotype
46	abolished serine/threonine-protein kinase activity.

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-1632852	Macroautophagy
R-HSA-5357905	Regulation of TNFR1 signaling
R-HSA-8854214	TBC/RABGAPs
R-HSA-8876198	RAB GEFs exchange GTP for GDP on RABs
R-HSA-8934903	Receptor Mediated Mitophagy

MSigDB gene sets: 346 (showing top): GOBP_NEGATIVE_REGULATION_OF_PROTEIN_CONTAINING_COMPLEX_ASSEMBLY, AP1_01, GOBP_REGULATION_OF_AUTOPHAGY, GOBP_NEGATIVE_REGULATION_OF_CELL_DEVELOPMENT, GOBP_REGULATION_OF_COLLATERAL_SPROUTING, MODULE_169, GOBP_NEURON_PROJECTION_EXTENSION, GOBP_VACUOLE_ORGANIZATION, GOBP_RESPONSE_TO_PEPTIDE, GOBP_LIPOPROTEIN_METABOLIC_PROCESS, GOCC_VACUOLAR_MEMBRANE, GOBP_REGULATION_OF_DEVELOPMENTAL_GROWTH, PEREZ_TP63_TARGETS, ENK_UV_RESPONSE_KERATINOCYTE_UP, GOBP_POSITIVE_REGULATION_OF_VACUOLE_ORGANIZATION

GO Biological Process (28): autophagosome assembly (GO:0000045), mitophagy (GO:0000423), protein phosphorylation (GO:0006468), autophagy (GO:0006914), signal transduction (GO:0007165), intracellular protein localization (GO:0008104), negative regulation of cell population proliferation (GO:0008285), regulation of autophagy (GO:0010506), positive regulation of autophagy (GO:0010508), regulation of tumor necrosis factor-mediated signaling pathway (GO:0010803), macroautophagy (GO:0016236), regulation of macroautophagy (GO:0016241), peptidyl-serine phosphorylation (GO:0018105), neuron projection regeneration (GO:0031102), neuron projection development (GO:0031175), negative regulation of protein-containing complex assembly (GO:0031333), cellular response to nutrient levels (GO:0031669), cellular response to stress (GO:0033554), piecemeal microautophagy of the nucleus (GO:0034727), response to starvation (GO:0042594), protein autophosphorylation (GO:0046777), negative regulation of collateral sprouting (GO:0048671), axon extension (GO:0048675), reticulophagy (GO:0061709), positive regulation of autophagosome assembly (GO:2000786), ubiquitin-dependent protein catabolic process (GO:0006511), axonogenesis (GO:0007409), protein-containing complex assembly (GO:0065003)

GO Molecular Function (12): protein serine/threonine kinase activity (GO:0004674), ATP binding (GO:0005524), small GTPase binding (GO:0031267), identical protein binding (GO:0042802), protein-containing complex binding (GO:0044877), GTPase binding (GO:0051020), protein serine kinase activity (GO:0106310), nucleotide binding (GO:0000166), protein kinase activity (GO:0004672), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (12): phagophore assembly site (GO:0000407), autophagosome membrane (GO:0000421), cytoplasm (GO:0005737), mitochondrial outer membrane (GO:0005741), autophagosome (GO:0005776), endoplasmic reticulum membrane (GO:0005789), cytosol (GO:0005829), axon (GO:0030424), phagophore assembly site membrane (GO:0034045), recycling endosome (GO:0055037), omegasome membrane (GO:1903349), Atg1/ULK1 kinase complex (GO:1990316)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Rab regulation of trafficking	2
Autophagy	1
TNF signaling	1
Mitophagy	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular response to stimulus	3
autophagy	3
cytoplasm	3
cellular anatomical structure	3
macroautophagy	2
regulation of autophagy	2
response to nutrient levels	2
response to stress	2
protein kinase activity	2
binding	2
Atg12 activating enzyme activity	1
protein-phosphatidylethanolamide deconjugating activity	1
Atg12 conjugating enzyme activity	1
Atg12 ligase activity	1
organelle assembly	1
Atg1/ULK1 kinase complex assembly	1
autophagosome organization	1
autophagy of mitochondrion	1
phosphorylation	1
protein modification process	1
catabolic process	1
transmembrane transport	1
process utilizing autophagic mechanism	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
macromolecule localization	1
cell population proliferation	1
regulation of cell population proliferation	1
negative regulation of cellular process	1
regulation of catabolic process	1
positive regulation of catabolic process	1
regulation of cytokine-mediated signaling pathway	1
tumor necrosis factor-mediated signaling pathway	1
autophagosome assembly	1
protein phosphorylation	1
peptidyl-serine modification	1
regeneration	1
neuron projection development	1

Protein interactions and networks

STRING

2512 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ULK1	RB1CC1	Q8TDY2	999
ULK1	ATG13	O75143	999
ULK1	ATG101	Q9BSB4	998
ULK1	BECN1	Q14457	995
ULK1	GABARAPL2	P60520	982
ULK1	ATG5	Q9H1Y0	975
ULK1	MTOR	P42345	972
ULK1	ATG12	O94817	969
ULK1	ATG3	Q9NT62	964
ULK1	ULK2	Q8IYT8	964
ULK1	PIK3C3	Q8NEB9	963
ULK1	GABARAP	O95166	958
ULK1	ATG7	O95352	955
ULK1	F5GZY7	F5GZY7	944
ULK1	MAP1LC3B	Q9GZQ8	914

IntAct

141 interactions, top by confidence:

A	B	Type	Score
ATG101	ATG13	psi-mi:“MI:0914”(association)	0.950
ATG13	ULK1	psi-mi:“MI:0914”(association)	0.940
ULK1	ATG13	psi-mi:“MI:0914”(association)	0.940
ULK1	ATG13	psi-mi:“MI:0915”(physical association)	0.940
ATG13	ULK1	psi-mi:“MI:2364”(proximity)	0.940
ULK1	RB1CC1	psi-mi:“MI:0915”(physical association)	0.910
RB1CC1	ATG13	psi-mi:“MI:0914”(association)	0.820
MAP1LC3C	ATG13	psi-mi:“MI:0914”(association)	0.750
MAP1LC3B	ATG13	psi-mi:“MI:0914”(association)	0.730
MAP1LC3C	ULK1	psi-mi:“MI:0407”(direct interaction)	0.730
ULK1	MAP1LC3C	psi-mi:“MI:0915”(physical association)	0.730
	ULK1	psi-mi:“MI:0915”(physical association)	0.700
ULK1		psi-mi:“MI:0915”(physical association)	0.700

BioGRID (615): ULK1 (Affinity Capture-Western), ULK1 (Affinity Capture-Western), ULK1 (Two-hybrid), DAPK3 (Affinity Capture-Western), RAB1A (Affinity Capture-Western), MUL1 (Affinity Capture-Western), ULK1 (Affinity Capture-Western), ULK1 (Reconstituted Complex), ULK1 (Affinity Capture-Western), ULK1 (Biochemical Activity), SQSTM1 (Biochemical Activity), SQSTM1 (Affinity Capture-Western), ULK1 (Affinity Capture-Western), ULK1 (Affinity Capture-Western), ULK1 (Reconstituted Complex)

ESM2 similar proteins: A0JPN4, A2A288, A2ARK0, A6ND36, A6QQJ8, A7E316, E9Q0S6, E9Q2Z1, O15037, O54714, O54967, O70260, O70405, O75385, O94983, P42335, P48778, Q07912, Q0P4K8, Q17R13, Q1LVK9, Q32PJ7, Q4V8I3, Q5D1E7, Q5D1E8, Q5DTV4, Q5HYM0, Q5JV73, Q5SWY7, Q5SXM2, Q5U2X5, Q5XIS1, Q68CZ2, Q6A037, Q6IRU7, Q6P1H6, Q6S5L8, Q7TP65, Q7TSG2, Q80U38

Diamond homologs: A1CHL6, A1CX69, A2QIL5, A6RYB8, A6ZU07, A7F0W2, A7KAL2, A7TIZ4, A8WYE4, B2DD29, D3ZHP7, D3ZML2, F4I1N8, F4IRW0, F4JBP3, I1RNG8, J4W0G2, O08678, O08679, O42844, O70405, O75385, O94547, P0CP70, P0CP71, P25323, P27448, P32562, P53104, P87248, P92937, Q03141, Q05512, Q0CLX3, Q0JI49, Q0UY20, Q10LQ2, Q19469, Q1DN93, Q23023

SIGNOR signaling

71 interactions.

A	Effect	B	Mechanism
ULK1	up-regulates	AMBRA1	phosphorylation
PRKAA2	up-regulates	ULK1	phosphorylation
MTOR	“down-regulates activity”	ULK1	phosphorylation
PRKAA1	“up-regulates activity”	ULK1	phosphorylation
PRKAB1	up-regulates	ULK1	phosphorylation
ULK1	“down-regulates activity”	PRKAA1	phosphorylation
ULK1	down-regulates	PRKAA2	phosphorylation
ULK1	down-regulates	PRKAG3	phosphorylation
ULK1	up-regulates	ATG13	phosphorylation
ULK1	up-regulates	RB1CC1	phosphorylation
ULK1	“form complex”	ULK1/Atg13/Fip200	binding
AMPK	up-regulates	ULK1	phosphorylation
mTORC1	down-regulates	ULK1	phosphorylation
ULK1	down-regulates	AMPK	phosphorylation
SMCR8	“down-regulates activity”	ULK1	binding
SMCR8	“down-regulates quantity”	ULK1	“transcriptional regulation”
RAB1A	“up-regulates activity”	ULK1	relocalization

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 73 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	5	63.4×	6e-07
Macroautophagy	18	39.2×	4e-22
Autophagy	14	39.2×	6e-17
Energy dependent regulation of mTOR by LKB1-AMPK	5	37.1×	7e-06
Selective autophagy	7	36.8×	7e-08
MTOR signalling	6	30.1×	2e-06
TP53 Regulates Metabolic Genes	12	29.4×	7e-13
Translocation of SLC2A4 (GLUT4) to the plasma membrane	7	20.4×	2e-06

GO biological processes:

GO term	Partners	Fold	FDR
mitophagy	12	58.7×	6e-16
autophagosome assembly	13	44.9×	6e-16
cellular response to nutrient levels	5	36.0×	2e-05
autophagosome maturation	6	32.4×	4e-06
cellular response to glucose starvation	6	31.1×	4e-06
macroautophagy	8	29.6×	5e-08
positive regulation of autophagy	8	25.6×	1e-07
negative regulation of TORC1 signaling	5	24.9×	1e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

240 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	177
Likely benign	12
Benign	9

Top pathogenic / likely-pathogenic (0)

SpliceAI

4859 predictions. Top by Δscore:

Variant	Effect	Δscore
12:131895109:CGAGG:C	donor_loss	1.0000
12:131895110:GAGG:G	donor_loss	1.0000
12:131895112:GGTG:G	donor_loss	1.0000
12:131895113:GTG:G	donor_loss	1.0000
12:131895114:T:G	donor_loss	1.0000
12:131895599:A:AG	acceptor_gain	1.0000
12:131895600:G:GA	acceptor_gain	1.0000
12:131895690:GAAG:G	donor_gain	1.0000
12:131895691:AAG:A	donor_gain	1.0000
12:131895691:AAGG:A	donor_loss	1.0000
12:131895692:AG:A	donor_gain	1.0000
12:131895692:AGGTG:A	donor_loss	1.0000
12:131895693:GG:G	donor_gain	1.0000
12:131895694:G:C	donor_loss	1.0000
12:131895694:G:GG	donor_gain	1.0000
12:131895775:T:A	acceptor_gain	1.0000
12:131895777:TCCTA:T	acceptor_loss	1.0000
12:131895778:CCTAG:C	acceptor_loss	1.0000
12:131895779:CTAGG:C	acceptor_loss	1.0000
12:131895780:TAGG:T	acceptor_loss	1.0000
12:131895781:A:AG	acceptor_gain	1.0000
12:131895781:AG:A	acceptor_gain	1.0000
12:131895782:G:GG	acceptor_gain	1.0000
12:131895782:GG:G	acceptor_gain	1.0000
12:131895782:GGA:G	acceptor_gain	1.0000
12:131895782:GGAA:G	acceptor_gain	1.0000
12:131895821:CCAGG:C	donor_loss	1.0000
12:131895822:CAGGT:C	donor_loss	1.0000
12:131895823:AGGT:A	donor_loss	1.0000
12:131895824:GGTAA:G	donor_loss	1.0000

AlphaMissense

6797 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:131895041:T:C	F14L	1.000
12:131895043:C:A	F14L	1.000
12:131895043:C:G	F14L	1.000
12:131895068:G:C	G23R	1.000
12:131895069:G:A	G23D	1.000
12:131895074:G:A	G25S	1.000
12:131895074:G:C	G25R	1.000
12:131895074:G:T	G25C	1.000
12:131895075:G:A	G25D	1.000
12:131895075:G:T	G25V	1.000
12:131895080:T:A	F27I	1.000
12:131895080:T:C	F27L	1.000
12:131895080:T:G	F27V	1.000
12:131895081:T:C	F27S	1.000
12:131895081:T:G	F27C	1.000
12:131895082:C:A	F27L	1.000
12:131895082:C:G	F27L	1.000
12:131895083:G:C	A28P	1.000
12:131895084:C:A	A28E	1.000
12:131895090:T:A	V30D	1.000
12:131895092:T:C	F31L	1.000
12:131895093:T:C	F31S	1.000
12:131895094:C:A	F31L	1.000
12:131895094:C:G	F31L	1.000
12:131895098:G:C	G33R	1.000
12:131895099:G:A	G33D	1.000
12:131895617:T:A	V43D	1.000
12:131895620:C:A	A44D	1.000
12:131895623:T:A	V45D	1.000
12:131895625:A:C	K46Q	1.000

dbSNP variants (sampled 300 via entrez): RS1000184016 (12:131900677 C>G), RS1000200073 (12:131896000 C>G,T), RS1000292485 (12:131918381 G>A,C), RS1000378314 (12:131921879 C>A,T), RS1000530253 (12:131917732 A>G), RS1000550594 (12:131915733 C>A), RS1000573644 (12:131913966 C>A,T), RS1000694272 (12:131905984 C>T), RS1000838924 (12:131909763 C>G,T), RS1000898244 (12:131910961 C>T), RS1000947318 (12:131904766 G>A), RS1000964459 (12:131917817 A>G), RS1000978264 (12:131904939 G>A), RS1001201687 (12:131919664 G>A,C), RS1001207675 (12:131909614 T>C)

Disease associations

OMIM: gene MIM:603168 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST002927_1	Mercury levels	5.000000e-06
GCST005951_3	Body mass index	6.000000e-09

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6006 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

24 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 160,994 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1287853	FEDRATINIB	4	3,554
CHEMBL1789941	RUXOLITINIB	4	11,547
CHEMBL2028663	DABRAFENIB	4	12,430
CHEMBL2105759	BARICITINIB	4	6,741
CHEMBL288441	BOSUTINIB	4	12,255
CHEMBL502835	NINTEDANIB	4	8,545
CHEMBL535	SUNITINIB	4	79,020
CHEMBL601719	CRIZOTINIB	4	14,403
CHEMBL2105728	CRENOLANIB	3	2,167
CHEMBL522892	DOVITINIB	3	4,944
CHEMBL603469	LESTAURTINIB	3
CHEMBL1230165	SILMITASERTIB	2	593
CHEMBL1721885	SU-014813	2	363
CHEMBL475251	R-406	2	762
CHEMBL564829	MILCICLIB	2	821
CHEMBL6068018	INLEXISERTIB	2	13
CHEMBL1230607	PHA-793887	1	299
CHEMBL1908397	KW-2449	1	622
CHEMBL2041933	AZD-7762	1	1,240
CHEMBL2140408	AMG-900	1	675
CHEMBL296468	BMS-387032	1
CHEMBL4289017	PF-03814735	1
CHEMBL494089	GSK-690693	1
CHEMBL574738	AST-487	1

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — Unc-51-like kinase (ULK) family

Most potent curated ligand interactions (3 total), top 3:

Ligand	Action	Affinity	Parameter
SBP-7455	Inhibition	7.89	pIC50
inlexisertib	Inhibition	7.6	pIC50
SBI-0206965	Inhibition	6.89	pIC50

Binding affinities (BindingDB)

124 measured of 517 human assays (769 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
4-(1-aminoethyl)-N-(2-thiophen-3-yl-1H-pyrrolo[2,3-b]pyridin-4-yl)cyclohexane-1-carboxamide	IC50	5 nM	US-12473284: Small molecule inhibitors of ULK1
US12473284, Compound MSK-A185	IC50	12.1 nM	US-12473284: Small molecule inhibitors of ULK1
US12473284, Compound MSK-A184-1	IC50	15.5 nM	US-12473284: Small molecule inhibitors of ULK1
US12473284, Compound MSK-A195	IC50	15.6 nM	US-12473284: Small molecule inhibitors of ULK1
4-(1-aminoethyl)-N-(2-phenyl-1H-pyrrolo[2,3-b]pyridin-4-yl)cyclohexane-1-carboxamide	IC50	18 nM	US-12473284: Small molecule inhibitors of ULK1
US12473284, Compound MSK-A189	IC50	18.3 nM	US-12473284: Small molecule inhibitors of ULK1
US12473284, Compound MSK-A184	IC50	18.9 nM	US-12473284: Small molecule inhibitors of ULK1
US12473284, Compound MSK-A188	IC50	19.4 nM	US-12473284: Small molecule inhibitors of ULK1
US12473284, Compound MSK-A192	IC50	20.2 nM	US-12473284: Small molecule inhibitors of ULK1
US12473284, Compound MSK-A191	IC50	20.6 nM	US-12473284: Small molecule inhibitors of ULK1
US12473284, Compound MSK-A196	IC50	20.8 nM	US-12473284: Small molecule inhibitors of ULK1
US12473284, Compound MSK-A182	IC50	22.9 nM	US-12473284: Small molecule inhibitors of ULK1
US12473284, Compound MSK-A176-2	IC50	23.6 nM	US-12473284: Small molecule inhibitors of ULK1
US12473284, Compound MSK-A190	IC50	23.8 nM	US-12473284: Small molecule inhibitors of ULK1
US12473284, Compound MSK-A197	IC50	25.7 nM	US-12473284: Small molecule inhibitors of ULK1
US12473284, Compound MSK-A193	IC50	26.3 nM	US-12473284: Small molecule inhibitors of ULK1
US12473284, Compound MSK-A194	IC50	29.2 nM	US-12473284: Small molecule inhibitors of ULK1
US12473284, Compound MSK-A186	IC50	29.8 nM	US-12473284: Small molecule inhibitors of ULK1
5-(2-((7-chloro-1,2,3,4- tetrahydroisoquinolin-6-yl)amino)- 5-(trifluoromethyl)pyrimidin-4-yl)- N,N-dimethylthiophene-3- carboxamide	IC50	30 nM	US-20250144094: THIOPHENE ULK1/2 INHIBITORS AND THEIR USE THEREOF
7-chloro-N-(4-(4-(4,5- dihydrooxazol-2-yl)thiophen-2-yl)- 5-(trifluoromethyl)pyrimidin-2-yl)- 1,2,3,4-tetrahydroisoquinolin-6- amine	IC50	30 nM	US-20250144094: THIOPHENE ULK1/2 INHIBITORS AND THEIR USE THEREOF
5-(2-((7-chloro-2-(1- methylazetidin-3-yl)-1,2,3,4- tetrahydroisoquinolin-6-yl)amino)- 5-(trifluoromethyl)pyrimidin-4- yl)thiophene-3-carboxamide	IC50	30 nM	US-20250144094: THIOPHENE ULK1/2 INHIBITORS AND THEIR USE THEREOF
N-(4-(4-aminothiophen-2-yl)-5- (trifluoromethyl)pyrimidin-2-yl)-7- chloro-1,2,3,4- tetrahydroisoquinolin-6-amine	IC50	30 nM	US-20250144094: THIOPHENE ULK1/2 INHIBITORS AND THEIR USE THEREOF
7-Chloro-N-(4-(4-(oxazol-2- yl)thiophen-2-yl)-5- (trifluoromethyl)pyrimidin-2-yl)- 1,2,3,4-tetrahydroisoquinolin-6- amine	IC50	30 nM	US-20250144094: THIOPHENE ULK1/2 INHIBITORS AND THEIR USE THEREOF
5-(2-((6-Ethyl-2-methylisoindolin- 5-yl)amino)-5- (trifluoromethyl)pyrimidin-4- yl)thiophene-3-carboxamide	IC50	30 nM	US-20250144094: THIOPHENE ULK1/2 INHIBITORS AND THEIR USE THEREOF
2-(2-((7-Chloro-1,2,3,4- tetrahydroisoquinolin-6-yl)amino)- 5-(trifluoromethyl)pyrimidin-4- yl)thieno[2,3-d]pyridazin-4(5H)- one	IC50	30 nM	US-20250144094: THIOPHENE ULK1/2 INHIBITORS AND THEIR USE THEREOF
5-(2-((7-Chloro-1,2,3,4- tetrahydroisoquinolin-6-yl)amino)- 5-(trifluoromethyl)pyrimidin-4- yl)thiophene-3-carbonitrile	IC50	30 nM	US-20250144094: THIOPHENE ULK1/2 INHIBITORS AND THEIR USE THEREOF
(5-(2-((7-Chloro-1,2,3,4- tetrahydroisoquinolin-6-yl)amino)- 5-(trifluoromethyl)pyrimidin-4- yl)thiophen-3- yl)dimethylphosphine oxide	IC50	30 nM	US-20250144094: THIOPHENE ULK1/2 INHIBITORS AND THEIR USE THEREOF
2-(2-((7-chloro-1,2,3,4- tetrahydroisoquinolin-6-yl)amino)- 5-(trifluoromethyl)pyrimidin-4-yl)- 5-(2-methoxyethyl)-5,6,7,8- tetrahydro-4H-thieno[3,2-c]azepin- 4-one	IC50	30 nM	US-20250144094: THIOPHENE ULK1/2 INHIBITORS AND THEIR USE THEREOF
7-chloro-N-(4-(4-(methylsulfonyl)- 5-(morpholinomethyl)thiophen-2- yl)-5-(trifluoromethyl)pyrimidin-2- yl)-1,2,3,4-tetrahydroisoquinolin-6- amine	IC50	30 nM	US-20250144094: THIOPHENE ULK1/2 INHIBITORS AND THEIR USE THEREOF
7-chloro-2-methyl-N-(4-(4- (methylsulfonyl)-5- (morpholinomethyl)thiophen-2-yl)- 5-(trifluoromethyl)pyrimidin-2-yl)- 1,2,3,4-tetrahydroisoquinolin-6- amine	IC50	30 nM	US-20250144094: THIOPHENE ULK1/2 INHIBITORS AND THEIR USE THEREOF
7-[2-[[7-chloro-2-(2,2,2-trifluoroacetyl)-3,4-dihydro-1H-isoquinolin-6-yl]amino]-5-(trifluoromethyl)pyrimidin-4-yl]-3,4-dihydro-2H-thieno[3,2-f][1,4]oxazepin-5-one	IC50	30 nM	US-20250144094: THIOPHENE ULK1/2 INHIBITORS AND THEIR USE THEREOF
6-ethyl-2-methyl-N-(4-(4- (methylsulfonyl)thiophen-2-yl)-5- (trifluoromethyl)pyrimidin-2- yl)isoindolin-5-amine	IC50	30 nM	US-20250144094: THIOPHENE ULK1/2 INHIBITORS AND THEIR USE THEREOF
7-chloro-N-(5-cyclopropyl-4-(4- (methylsulfonyl)thiophen-2- yl)pyrimidin-2-yl)-1,2,3,4- tetrahydroisoquinolin-6-amine	IC50	30 nM	US-20250144094: THIOPHENE ULK1/2 INHIBITORS AND THEIR USE THEREOF
7-chloro-N-(4-(5-(methoxymethyl)- 4-(methylsulfonyl)thiophen-2-yl)- 5-(trifluoromethyl)pyrimidin-2-yl)- 1,2,3,4-tetrahydroisoquinolin-6- amine	IC50	30 nM	US-20250144094: THIOPHENE ULK1/2 INHIBITORS AND THEIR USE THEREOF
7-chloro-2-cyclopropyl-N-[4-(4- methylsulfonyl-2-thienyl)-5- (trifluoromethyl)pyrimidin-2-yl]- 3,4-dihydro-1H-isoquinolin-6- amine	IC50	30 nM	US-20250144094: THIOPHENE ULK1/2 INHIBITORS AND THEIR USE THEREOF
6-chloro-2-cyclopropyl-N-[4-(4- methylsulfonyl-2-thienyl)-5- (trifluoromethyl)pyrimidin-2- yl]isoindolin-5-amine	IC50	30 nM	US-20250144094: THIOPHENE ULK1/2 INHIBITORS AND THEIR USE THEREOF
2-cyclopropyl-6-fluoro-N-[4-(4- methylsulfonyl-2-thienyl)-5- (trifluoromethyl)pyrimidin-2- yl]isoindolin-5-amine	IC50	30 nM	US-20250144094: THIOPHENE ULK1/2 INHIBITORS AND THEIR USE THEREOF
2-cyclopropyl-7-fluoro-N-[4-(4- methylsulfonyl-2-thienyl)-5- (trifluoromethyl)pyrimidin-2-yl]- 3,4-dihydro-1H-isoquinolin-6- amine	IC50	30 nM	US-20250144094: THIOPHENE ULK1/2 INHIBITORS AND THEIR USE THEREOF
N-[3-methyl-1-(1-methylazetidin-3- yl)pyrazol-4-yl]-4-(4- methylsulfonyl-2-thienyl)-5- (trifluoromethyl)pyrimidin-2-amine	IC50	30 nM	US-20250144094: THIOPHENE ULK1/2 INHIBITORS AND THEIR USE THEREOF
N-(1-(azetidin-3-yl)-3-methyl-1H- pyrazol-4-yl)-4-(4- (methylsulfonyl)thiophen-2-yl)-5- (trifluoromethyl)pyrimidin-2-amine	IC50	30 nM	US-20250144094: THIOPHENE ULK1/2 INHIBITORS AND THEIR USE THEREOF
7-(2-((7-chloro-2-cyclopropyl- 1,2,3,4-tetrahydroisoquinolin-6- yl)amino)-5- (trifluoromethyl)pyrimidin-4-yl)- 3,4-dihydrothieno[2,3- f][1,4]thiazepin-5(2H)-one 1,1- dioxide	IC50	30 nM	US-20250144094: THIOPHENE ULK1/2 INHIBITORS AND THEIR USE THEREOF
US12473284, Compound MSK-A184-2	IC50	38.9 nM	US-12473284: Small molecule inhibitors of ULK1
US12473284, Compound MSK-A200	IC50	39.2 nM	US-12473284: Small molecule inhibitors of ULK1
US12473284, Compound MSK-A187	IC50	40.5 nM	US-12473284: Small molecule inhibitors of ULK1
US12473284, Compound MSK-A191-1	IC50	40.8 nM	US-12473284: Small molecule inhibitors of ULK1
US12473284, Compound MSK-A198	IC50	43.3 nM	US-12473284: Small molecule inhibitors of ULK1
US12473284, Compound MSK-A178	IC50	47 nM	US-12473284: Small molecule inhibitors of ULK1
US12473284, Compound MSK-A177	IC50	54 nM	US-12473284: Small molecule inhibitors of ULK1
US12473284, Compound MSK-A176-1	IC50	56.2 nM	US-12473284: Small molecule inhibitors of ULK1
US12473284, Compound MSK-A191-2	IC50	59.1 nM	US-12473284: Small molecule inhibitors of ULK1

ChEMBL bioactivities

395 potent at pChembl≥5 of 400 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.08	Kd	0.83	nM	TAE-684
8.82	Kd	1.5	nM	CHEMBL5570377
8.80	IC50	1.6	nM	CHEMBL5280560
8.80	IC50	1.6	nM	CHEMBL5568152
8.80	IC50	1.585	nM	CHEMBL5571775
8.80	IC50	1.585	nM	CHEMBL5570377
8.70	IC50	1.995	nM	CHEMBL5571896
8.70	IC50	1.995	nM	CHEMBL5564752
8.70	IC50	1.995	nM	CHEMBL5569162
8.70	IC50	1.995	nM	CHEMBL5570377
8.60	IC50	2.512	nM	CHEMBL5564752
8.54	IC50	2.9	nM	CHEMBL3605057
8.54	IC50	2.9	nM	CHEMBL4516990
8.54	IC50	2.9	nM	CHEMBL5266681
8.52	IC50	3	nM	CHEMBL4796600
8.50	IC50	3.162	nM	CHEMBL5569162
8.50	IC50	3.162	nM	CHEMBL5572614
8.50	IC50	3.162	nM	CHEMBL5563000
8.40	IC50	3.981	nM	CHEMBL5571896
8.40	IC50	3.981	nM	CHEMBL5590601
8.30	IC50	5	nM	CHEMBL4746440
8.30	IC50	5	nM	CHEMBL4741912
8.30	IC50	5.012	nM	CHEMBL5563000
8.30	IC50	5.012	nM	CHEMBL5591655
8.30	IC50	5.012	nM	CHEMBL5591974
8.30	IC50	5.012	nM	CHEMBL5573979
8.30	IC50	5.012	nM	CHEMBL5571775
8.30	EC50	5.012	nM	CHEMBL5570377
8.28	IC50	5.3	nM	CHEMBL3605055
8.22	IC50	6	nM	CHEMBL4782961
8.22	IC50	6	nM	INLEXISERTIB
8.15	IC50	7	nM	CHEMBL4758769
8.10	IC50	8	nM	CHEMBL3605055
8.10	IC50	7.943	nM	CHEMBL5569586
8.10	IC50	7.943	nM	CHEMBL5573979
8.10	IC50	7.943	nM	CHEMBL5574119
8.10	IC50	7.943	nM	CHEMBL5572614
8.08	IC50	8.3	nM	CHEMBL5269042
8.08	IC50	8.3	nM	CHEMBL4744680
8.05	IC50	8.95	nM	STAUROSPORINE
8.05	IC50	9	nM	CHEMBL4435393
8.04	IC50	9.2	nM	STAUROSPORINE
8.00	IC50	10	nM	CHEMBL4744680
8.00	IC50	10	nM	CHEMBL5579740
8.00	IC50	10	nM	CHEMBL5564752
8.00	IC50	10	nM	CHEMBL5570377
8.00	Kd	9.9	nM	STAUROSPORINE
7.99	IC50	10.3	nM	STAUROSPORINE
7.96	IC50	11	nM	CHEMBL4167070
7.90	IC50	12.59	nM	CHEMBL5590601

PubChem BioAssay actives

276 with measured affinity, of 1060 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
5-chloro-2-N-[2-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl]-4-N-(2-propan-2-ylsulfonylphenyl)pyrimidine-2,4-diamine	624916: Binding constant for ULK1 kinase domain	kd	0.0008	uM
4-[2-(1,2,3,6-tetrahydropyridin-5-yl)-1H-pyrrolo[2,3-b]pyridin-5-yl]-N-(2,2,2-trifluoroethyl)thiophene-2-carboxamide	2101095: Binding affinity to 6His/GFP-tagged ULK1 kinase domain (1 to 283 residues) (unknown origin) expressed in Escherichia coli BL21 DE3 cells assessed as dissociation constant incubated for 5 mins by MST analysis	kd	0.0015	uM
4-[2-(3,6-dihydro-2H-pyran-4-yl)-1H-pyrrolo[2,3-b]pyridin-5-yl]-N-(2,2,2-trifluoroethyl)thiophene-2-carboxamide	2101090: Binding affinity to GST tagged ULK1 kinase domain (1 to 283 residues) (unknown origin) expressed in Escherichia coli BL21 DE3 cells incubated for 1 hr by fluorescence based lanthascreen assay	ic50	0.0016	uM
4-[5-[4-(2-piperidin-1-ylethoxy)phenyl]-1,2-dihydropyrazolo[1,5-a]pyrimidin-2-yl]-N-[(2S)-1,1,1-trifluoro-3-methylbutan-2-yl]thiophene-2-carboxamide	1946672: Inhibition of ULK1 (unknown origin)	ic50	0.0016	uM
4-[6-[4-(2-piperidin-1-ylethoxy)phenyl]pyrazolo[1,5-a]pyrimidin-3-yl]-N-[(2S)-1,1,1-trifluoro-3-methylbutan-2-yl]thiophene-2-carboxamide	2074633: Inhibition of ULK1 (unknown origin)	ic50	0.0016	uM
4-[2-(1-methyl-3,6-dihydro-2H-pyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-5-yl]-N-(2,2,2-trifluoroethyl)thiophene-2-carboxamide	2101091: Inhibition of ULK1 kinase domain (1 to 283 residues) (unknown origin) expressed in Escherichia coli BL21 DE3 cells preincubated for 20 mins in presence of ATP followed by 33P-ATP addition and measured after 2 hrs by radiometric hotspot kinase assay	ic50	0.0020	uM
5-[2-(4-fluorophenyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]-N-(2,2,2-trifluoroethyl)furan-2-carboxamide	2101091: Inhibition of ULK1 kinase domain (1 to 283 residues) (unknown origin) expressed in Escherichia coli BL21 DE3 cells preincubated for 20 mins in presence of ATP followed by 33P-ATP addition and measured after 2 hrs by radiometric hotspot kinase assay	ic50	0.0020	uM
4-[2-(1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-5-yl]-N-(2,2,2-trifluoroethyl)thiophene-2-carboxamide	2101091: Inhibition of ULK1 kinase domain (1 to 283 residues) (unknown origin) expressed in Escherichia coli BL21 DE3 cells preincubated for 20 mins in presence of ATP followed by 33P-ATP addition and measured after 2 hrs by radiometric hotspot kinase assay	ic50	0.0020	uM
N-[3-[[5-cyclopropyl-2-[3-(morpholin-4-ylmethyl)anilino]pyrimidin-4-yl]amino]propyl]cyclopropanecarboxamide	1946672: Inhibition of ULK1 (unknown origin)	ic50	0.0029	uM
N-[3-[[5-cyclopropyl-2-[3-(morpholin-4-ylmethyl)anilino]pyrimidin-4-yl]amino]propyl]cyclobutanecarboxamide	1494457: Inhibition of GST-tagged ULK1 (unknown origin)	ic50	0.0029	uM
N-[3-[[5-cyclopropyl-2-[(2-methyl-3,4-dihydro-1H-isoquinolin-6-yl)amino]pyrimidin-4-yl]amino]propyl]cyclobutanecarboxamide	1512691: Inhibition of wild type GST-tagged ULK1 (unknown origin) after 5 mins in presence of gamma-[32]P-ATP by immunoblot analysis	ic50	0.0029	uM
6-[[4-(cyclopropylamino)-5-(trifluoromethyl)pyrimidin-2-yl]amino]-3,4-dihydro-2H-naphthalen-1-one	1682982: Inhibition of recombinant human ULK1 (1-649) expressed in Sf9 cells using myelin basic protein as substrate by ADP-glo assay	ic50	0.0030	uM
4-[2-[4-(2-morpholin-4-ylethoxy)phenyl]-1H-pyrrolo[2,3-b]pyridin-5-yl]-N-(2,2,2-trifluoroethyl)thiophene-2-carboxamide	2101091: Inhibition of ULK1 kinase domain (1 to 283 residues) (unknown origin) expressed in Escherichia coli BL21 DE3 cells preincubated for 20 mins in presence of ATP followed by 33P-ATP addition and measured after 2 hrs by radiometric hotspot kinase assay	ic50	0.0032	uM
4-[2-(2,5-dihydro-1H-pyrrol-3-yl)-1H-pyrrolo[2,3-b]pyridin-5-yl]-N-(2,2,2-trifluoroethyl)thiophene-2-carboxamide	2101091: Inhibition of ULK1 kinase domain (1 to 283 residues) (unknown origin) expressed in Escherichia coli BL21 DE3 cells preincubated for 20 mins in presence of ATP followed by 33P-ATP addition and measured after 2 hrs by radiometric hotspot kinase assay	ic50	0.0032	uM
4-[2-[4-(2-piperazin-1-ylethoxy)phenyl]-1H-pyrrolo[2,3-b]pyridin-5-yl]-N-(2,2,2-trifluoroethyl)thiophene-2-carboxamide	2101091: Inhibition of ULK1 kinase domain (1 to 283 residues) (unknown origin) expressed in Escherichia coli BL21 DE3 cells preincubated for 20 mins in presence of ATP followed by 33P-ATP addition and measured after 2 hrs by radiometric hotspot kinase assay	ic50	0.0040	uM
4-N-cyclopropyl-2-N-quinolin-6-yl-5-(trifluoromethyl)pyrimidine-2,4-diamine	1682982: Inhibition of recombinant human ULK1 (1-649) expressed in Sf9 cells using myelin basic protein as substrate by ADP-glo assay	ic50	0.0050	uM
2-N-(3H-benzimidazol-5-yl)-4-N-cyclopropyl-5-(trifluoromethyl)pyrimidine-2,4-diamine	1682982: Inhibition of recombinant human ULK1 (1-649) expressed in Sf9 cells using myelin basic protein as substrate by ADP-glo assay	ic50	0.0050	uM
4-(2-phenyl-1H-pyrrolo[2,3-b]pyridin-5-yl)-N-(2,2,2-trifluoroethyl)thiophene-2-carboxamide	2101091: Inhibition of ULK1 kinase domain (1 to 283 residues) (unknown origin) expressed in Escherichia coli BL21 DE3 cells preincubated for 20 mins in presence of ATP followed by 33P-ATP addition and measured after 2 hrs by radiometric hotspot kinase assay	ic50	0.0050	uM
4-[2-[4-[2-(4-methylpiperazin-1-yl)ethoxy]phenyl]-1H-pyrrolo[2,3-b]pyridin-5-yl]-N-(2,2,2-trifluoroethyl)thiophene-2-carboxamide	2101091: Inhibition of ULK1 kinase domain (1 to 283 residues) (unknown origin) expressed in Escherichia coli BL21 DE3 cells preincubated for 20 mins in presence of ATP followed by 33P-ATP addition and measured after 2 hrs by radiometric hotspot kinase assay	ic50	0.0050	uM
4-[2-(4-methoxyphenyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]-N-(2,2,2-trifluoroethyl)thiophene-2-carboxamide	2101091: Inhibition of ULK1 kinase domain (1 to 283 residues) (unknown origin) expressed in Escherichia coli BL21 DE3 cells preincubated for 20 mins in presence of ATP followed by 33P-ATP addition and measured after 2 hrs by radiometric hotspot kinase assay	ic50	0.0050	uM
2-N-(3H-benzimidazol-5-yl)-4-N-(5-cyclobutyl-1H-pyrazol-3-yl)quinazoline-2,4-diamine	1241330: Inhibition of SUMO-tagged ULK1 (unknown origin) kinase domain expressed in KRX cells using [32P]-gamma-ATP and myelin basic protein substrate incubated for 7 mins	ic50	0.0053	uM
2-N-(2H-benzotriazol-5-yl)-4-N-cyclopropyl-5-(trifluoromethyl)pyrimidine-2,4-diamine	1682982: Inhibition of recombinant human ULK1 (1-649) expressed in Sf9 cells using myelin basic protein as substrate by ADP-glo assay	ic50	0.0060	uM
4-N-cyclopropyl-2-N-(3,4-dihydro-2H-1,5-benzodioxepin-7-yl)-5-(trifluoromethyl)pyrimidine-2,4-diamine	1682982: Inhibition of recombinant human ULK1 (1-649) expressed in Sf9 cells using myelin basic protein as substrate by ADP-glo assay	ic50	0.0070	uM
4-[2-(4-fluorophenyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]-N-(2,2,2-trifluoroethyl)thiophene-2-carboxamide	2101090: Binding affinity to GST tagged ULK1 kinase domain (1 to 283 residues) (unknown origin) expressed in Escherichia coli BL21 DE3 cells incubated for 1 hr by fluorescence based lanthascreen assay	ic50	0.0079	uM
6-[2-(4-fluorophenyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]-N-(2,2,2-trifluoroethyl)pyridine-2-carboxamide	2101091: Inhibition of ULK1 kinase domain (1 to 283 residues) (unknown origin) expressed in Escherichia coli BL21 DE3 cells preincubated for 20 mins in presence of ATP followed by 33P-ATP addition and measured after 2 hrs by radiometric hotspot kinase assay	ic50	0.0079	uM
N-[(1S)-1-cyclopropyl-2,2,2-trifluoroethyl]-4-[6-(4-fluorophenyl)pyrazolo[1,5-a]pyrimidin-3-yl]thiophene-2-carboxamide	2074072: Inhibition of human ULK1 by discoverX kinome scan assay	ic50	0.0083	uM
N-[(1S)-1-cyclopropyl-2,2,2-trifluoroethyl]-4-[5-(4-fluorophenyl)-1,2-dihydropyrazolo[1,5-a]pyrimidin-2-yl]thiophene-2-carboxamide	1946672: Inhibition of ULK1 (unknown origin)	ic50	0.0083	uM
(2S,3R,4R,6R)-3-methoxy-2-methyl-4-(methylamino)-29-oxa-1,7,17-triazaoctacyclo[12.12.2.12,6.07,28.08,13.015,19.020,27.021,26]nonacosa-8,10,12,14,19,21,23,25,27-nonaen-16-one	1531922: Inhibition of human ULK1 using MBP as substrate by [gamma-33P]-ATP assay	ic50	0.0089	uM
1-[4-[(1R)-1-[2-[[6-[1-(cyclopropylmethyl)pyrazol-4-yl]-1H-benzimidazol-2-yl]amino]-4-pyridinyl]ethyl]piperazin-1-yl]-3,3,3-trifluoropropan-1-one	1582170: Inhibition of wild-type human partial length ULK1 (M1 to T309 residues) expressed in mammalian expression system by Kinomescan method	ic50	0.0090	uM
5-[2-(4-fluorophenyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]-N-(2,2,2-trifluoroethyl)-1,3-thiazole-2-carboxamide	2101090: Binding affinity to GST tagged ULK1 kinase domain (1 to 283 residues) (unknown origin) expressed in Escherichia coli BL21 DE3 cells incubated for 1 hr by fluorescence based lanthascreen assay	ic50	0.0100	uM
3-amino-N-[3-(naphthalen-1-ylamino)-1H-indazol-5-yl]cyclohexane-1-carboxamide	1504920: Inhibition of ATG13 binding to full-length ULK1 (unknown origin) expressed in HEK293T cells preincubated for 15 mins followed by human C-terminal FLAG-tagged ATG13 addition measured after 30 mins by Alphascreen assay	ic50	0.0110	uM
4-N-cyclopropyl-2-N-quinoxalin-6-yl-5-(trifluoromethyl)pyrimidine-2,4-diamine	1682982: Inhibition of recombinant human ULK1 (1-649) expressed in Sf9 cells using myelin basic protein as substrate by ADP-glo assay	ic50	0.0130	uM
N-[4-[[4-(cyclopropylamino)-5-(trifluoromethyl)pyrimidin-2-yl]amino]phenyl]cyclopropanecarboxamide	1682982: Inhibition of recombinant human ULK1 (1-649) expressed in Sf9 cells using myelin basic protein as substrate by ADP-glo assay	ic50	0.0130	uM
4-N-cyclopropyl-2-N-(3,4-dimethoxyphenyl)-5-(trifluoromethyl)pyrimidine-2,4-diamine	1682982: Inhibition of recombinant human ULK1 (1-649) expressed in Sf9 cells using myelin basic protein as substrate by ADP-glo assay	ic50	0.0130	uM
(3Z)-3-[(3,5-dichloro-4-hydroxyphenyl)methylidene]-5-(furan-2-carbonyl)-1H-indol-2-one	2074072: Inhibition of human ULK1 by discoverX kinome scan assay	ic50	0.0130	uM
methyl 4,6-di(propan-2-yloxy)-1H-indole-2-carboxylate	2074633: Inhibition of ULK1 (unknown origin)	ic50	0.0136	uM
6-[[5-fluoro-2-(3,4,5-trimethoxyanilino)pyrimidin-4-yl]amino]-2,2-dimethyl-4H-pyrido[3,2-b][1,4]oxazin-3-one	624916: Binding constant for ULK1 kinase domain	kd	0.0140	uM
4-N-cyclopropyl-2-N-(5-methoxy-3-pyridinyl)-5-(trifluoromethyl)pyrimidine-2,4-diamine	1682982: Inhibition of recombinant human ULK1 (1-649) expressed in Sf9 cells using myelin basic protein as substrate by ADP-glo assay	ic50	0.0140	uM
4-N-cyclopropyl-2-N-(1H-indazol-5-yl)-5-(trifluoromethyl)pyrimidine-2,4-diamine	1682982: Inhibition of recombinant human ULK1 (1-649) expressed in Sf9 cells using myelin basic protein as substrate by ADP-glo assay	ic50	0.0140	uM
4-N-cyclopropyl-2-N-(2,3-dihydro-1,4-benzodioxin-6-yl)-5-(trifluoromethyl)pyrimidine-2,4-diamine	1682982: Inhibition of recombinant human ULK1 (1-649) expressed in Sf9 cells using myelin basic protein as substrate by ADP-glo assay	ic50	0.0140	uM
4-[2-(2-fluorophenyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]-N-(2,2,2-trifluoroethyl)thiophene-2-carboxamide	2101091: Inhibition of ULK1 kinase domain (1 to 283 residues) (unknown origin) expressed in Escherichia coli BL21 DE3 cells preincubated for 20 mins in presence of ATP followed by 33P-ATP addition and measured after 2 hrs by radiometric hotspot kinase assay	ic50	0.0158	uM
3-[2-(4-fluorophenyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]-N-(2,2,2-trifluoroethyl)benzamide	2101091: Inhibition of ULK1 kinase domain (1 to 283 residues) (unknown origin) expressed in Escherichia coli BL21 DE3 cells preincubated for 20 mins in presence of ATP followed by 33P-ATP addition and measured after 2 hrs by radiometric hotspot kinase assay	ic50	0.0158	uM
4-[2-(3-fluorophenyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]-N-(2,2,2-trifluoroethyl)thiophene-2-carboxamide	2101091: Inhibition of ULK1 kinase domain (1 to 283 residues) (unknown origin) expressed in Escherichia coli BL21 DE3 cells preincubated for 20 mins in presence of ATP followed by 33P-ATP addition and measured after 2 hrs by radiometric hotspot kinase assay	ic50	0.0158	uM
4-[2-(4-fluorophenyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]-N-[(2S)-1-hydroxybutan-2-yl]thiophene-2-carboxamide	2101091: Inhibition of ULK1 kinase domain (1 to 283 residues) (unknown origin) expressed in Escherichia coli BL21 DE3 cells preincubated for 20 mins in presence of ATP followed by 33P-ATP addition and measured after 2 hrs by radiometric hotspot kinase assay	ic50	0.0158	uM
4-N-cyclopropyl-2-N-quinolin-3-yl-5-(trifluoromethyl)pyrimidine-2,4-diamine	1682982: Inhibition of recombinant human ULK1 (1-649) expressed in Sf9 cells using myelin basic protein as substrate by ADP-glo assay	ic50	0.0160	uM
4-N-cyclobutyl-2-N-(1H-pyrrolo[2,3-b]pyridin-5-yl)-5-(trifluoromethyl)pyrimidine-2,4-diamine	1682982: Inhibition of recombinant human ULK1 (1-649) expressed in Sf9 cells using myelin basic protein as substrate by ADP-glo assay	ic50	0.0170	uM
2-[bis(2-methylpropyl)amino]-1-[4-[2-(2,4-dichlorophenyl)-2-(naphthalen-2-ylmethoxy)ethyl]piperazin-1-yl]ethanone	1494459: Activation of recombinant human N-terminal GST-tagged ULK1 (1 to 649 residues) expressed in baculovirus infected Sf9 cells using MBP as substrate after 60 mins by ADP-Glo assay	ec50	0.0189	uM
2-N-(1,3-benzoxazol-6-yl)-4-N-cyclopropyl-5-(trifluoromethyl)pyrimidine-2,4-diamine	1682982: Inhibition of recombinant human ULK1 (1-649) expressed in Sf9 cells using myelin basic protein as substrate by ADP-glo assay	ic50	0.0190	uM
2-N-(4-aminophenyl)-4-N-cyclopropyl-5-(trifluoromethyl)pyrimidine-2,4-diamine	1682982: Inhibition of recombinant human ULK1 (1-649) expressed in Sf9 cells using myelin basic protein as substrate by ADP-glo assay	ic50	0.0200	uM
2-N-(1,3-benzodioxol-5-yl)-4-N-cyclopropyl-5-(trifluoromethyl)pyrimidine-2,4-diamine	1682982: Inhibition of recombinant human ULK1 (1-649) expressed in Sf9 cells using myelin basic protein as substrate by ADP-glo assay	ic50	0.0210	uM

CTD chemical–gene interactions

93 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases reaction, increases phosphorylation, affects reaction, decreases expression, increases expression	5
dorsomorphin	decreases expression, decreases reaction, increases phosphorylation, increases expression	5
3-methyladenine	decreases reaction, increases expression, affects cotreatment, decreases phosphorylation, decreases expression (+1 more)	4
Acetylcysteine	affects cotreatment, increases expression, decreases reaction, increases phosphorylation, decreases expression (+1 more)	3
Sirolimus	increases expression, increases reaction	3
tetrandrine	decreases expression, increases phosphorylation	2
arsenite	affects binding, decreases reaction, increases expression	2
tris(1,3-dichloro-2-propyl)phosphate	decreases reaction, increases phosphorylation, increases expression	2
Acetaminophen	decreases expression, increases expression	2
Benzo(a)pyrene	affects methylation	2
Ozone	affects expression, increases abundance, increases expression	2
Rotenone	decreases reaction, increases phosphorylation, increases expression	2
Tretinoin	decreases reaction, increases expression	2
Valproic Acid	increases methylation, affects expression	2
aristolochic acid I	increases expression	1
GSK-J4	increases expression	1
FR900359	affects phosphorylation	1
moringin	affects cotreatment, decreases expression	1
metarrestin	increases reaction, affects binding, decreases reaction	1
triphenyl phosphate	affects expression	1
1,12-benzoperylene	affects cotreatment, increases expression	1
4-biphenylamine	affects expression, affects reaction	1
bisphenol A	decreases methylation, affects cotreatment	1
emulphogene BC 720	increases expression	1
2,5,2’,5’-tetrachlorobiphenyl	increases expression, increases reaction	1
Nonidet P-40	decreases expression	1
acadesine	increases phosphorylation, increases reaction	1
cypermethrin	increases expression	1
fisetin	decreases expression, decreases reaction	1
cobaltous chloride	increases expression	1

ChEMBL screening assays

318 unique, capped per target: 318 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1021462	Binding	Inhibition of ULK1 assessed as enzyme activity relative to control	Examining the chirality, conformation and selective kinase inhibition of 3-((3R,4R)-4-methyl-3-(methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)piperidin-1-yl)-3-oxopropanenitrile (CP-690,550). — J Med Chem

Cellosaurus cell lines

11 cell lines: 9 cancer cell line, 1 transformed cell line, 1 spontaneously immortalized cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B9TY	Abcam A-549 ULK1 KO	Cancer cell line	Male
CVCL_C2VS	HeLa S3 penta KO-ULK1/ULK2 DKO	Cancer cell line	Female
CVCL_C2VT	HeLa S3 penta KO-TBK1/ULK1/ULK2 TKO	Cancer cell line	Female
CVCL_C9DW	HeLa S3 penta KO-ULK1/ULK2 DKO-AZI2/TBKBP1 DKO	Cancer cell line	Female
CVCL_D8D8	Ubigene A-549 ULK1 KO	Cancer cell line	Male
CVCL_D8XY	Ubigene HCT 116 ULK1 KO	Cancer cell line	Male
CVCL_D9VF	Ubigene HEK293 ULK1 KO	Transformed cell line	Female
CVCL_E0SJ	Ubigene HeLa ULK1 KO	Cancer cell line	Female
CVCL_E1DY	Ubigene U2OS ULK1 KO	Cancer cell line	Female
CVCL_F1YP	ARPE-19 ULK1 KO	Spontaneously immortalized cell line	Male

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.