PRKAG1

Summary

PRKAG1 (protein kinase AMP-activated non-catalytic subunit gamma 1, HGNC:9385) is a protein-coding gene on chromosome 12q13.12, encoding 5’-AMP-activated protein kinase subunit gamma-1 (P54619). AMP/ATP-binding subunit of AMP-activated protein kinase (AMPK), an energy sensor protein kinase that plays a key role in regulating cellular energy metabolism.

The protein encoded by this gene is a regulatory subunit of the AMP-activated protein kinase (AMPK). AMPK is a heterotrimer consisting of an alpha catalytic subunit, and non-catalytic beta and gamma subunits. AMPK is an important energy-sensing enzyme that monitors cellular energy status. In response to cellular metabolic stresses, AMPK is activated, and thus phosphorylates and inactivates acetyl-CoA carboxylase (ACC) and beta-hydroxy beta-methylglutaryl-CoA reductase (HMGCR), key enzymes involved in regulating de novo biosynthesis of fatty acid and cholesterol. This subunit is one of the gamma regulatory subunits of AMPK. Alternatively spliced transcript variants encoding distinct isoforms have been observed.

Source: NCBI Gene 5571 — RefSeq curated summary.

At a glance

• GWAS associations: 8
• Clinical variants (ClinVar): 4 total
• Druggable target: yes — 24 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_002733

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9385
Approved symbol	PRKAG1
Name	protein kinase AMP-activated non-catalytic subunit gamma 1
Location	12q13.12
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000181929
Ensembl biotype	protein_coding
OMIM	602742
Entrez	5571

Gene structure

Transcript identifiers

Ensembl transcripts: 20 — 14 protein_coding, 5 retained_intron, 1 nonsense_mediated_decay

ENST00000316299, ENST00000546531, ENST00000547082, ENST00000547125, ENST00000547306, ENST00000548065, ENST00000548362, ENST00000548605, ENST00000548857, ENST00000548950, ENST00000549726, ENST00000550125, ENST00000550448, ENST00000551121, ENST00000551696, ENST00000551770, ENST00000552212, ENST00000552463, ENST00000552657, ENST00000552793

RefSeq mRNA: 3 — MANE Select: NM_002733 NM_001206709, NM_001206710, NM_002733

CCDS: CCDS55824, CCDS55825, CCDS8777

Canonical transcript exons

ENST00000548065 — 12 exons

Exon	Start	End
ENSE00002332096	49002274	49003006
ENSE00002353613	49018732	49018776
ENSE00003465969	49003558	49003595
ENSE00003466184	49005743	49005852
ENSE00003495633	49004507	49004633
ENSE00003518369	49003144	49003290
ENSE00003527404	49013062	49013110
ENSE00003580650	49005462	49005543
ENSE00003622193	49005306	49005364
ENSE00003664521	49004964	49005018
ENSE00003678217	49003757	49003922
ENSE00003694715	49005120	49005165

Expression profiles

Bgee: expression breadth ubiquitous, 281 present calls, max score 96.79.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 23.2372 / max 148.5237, expressed in 1813 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
130783	19.7760	1808
130782	2.3875	1263
130784	0.8596	605
130781	0.0928	34
130779	0.0759	25
130780	0.0454	19

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
gastrocnemius	UBERON:0001388	96.79	gold quality
muscle of leg	UBERON:0001383	96.76	gold quality
islet of Langerhans	UBERON:0000006	96.44	gold quality
right adrenal gland cortex	UBERON:0035827	96.22	gold quality
right adrenal gland	UBERON:0001233	96.18	gold quality
heart left ventricle	UBERON:0002084	96.02	gold quality
left adrenal gland	UBERON:0001234	95.87	gold quality
cardiac ventricle	UBERON:0002082	95.83	gold quality
muscle organ	UBERON:0001630	95.77	gold quality
triceps brachii	UBERON:0001509	95.71	gold quality
hindlimb stylopod muscle	UBERON:0004252	95.67	gold quality
left adrenal gland cortex	UBERON:0035825	95.67	gold quality
right atrium auricular region	UBERON:0006631	95.65	gold quality
apex of heart	UBERON:0002098	95.45	gold quality
rectum	UBERON:0001052	95.42	gold quality
heart	UBERON:0000948	95.29	gold quality
cardiac atrium	UBERON:0002081	95.22	gold quality
lower esophagus muscularis layer	UBERON:0035833	95.14	gold quality
lower esophagus	UBERON:0013473	95.13	gold quality
calcaneal tendon	UBERON:0003701	95.12	gold quality
adrenal gland	UBERON:0002369	95.05	gold quality
gluteal muscle	UBERON:0002000	95.04	gold quality
adrenal cortex	UBERON:0001235	94.93	gold quality
skin of leg	UBERON:0001511	94.77	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	94.75	gold quality
right coronary artery	UBERON:0001625	94.61	gold quality
esophagus	UBERON:0001043	94.53	gold quality
body of pancreas	UBERON:0001150	94.52	gold quality
monocyte	CL:0000576	94.51	gold quality
skin of abdomen	UBERON:0001416	94.46	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.66

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

2 targets.

Target	Regulation
FLCN	Activation
FNIP1	Activation

miRNA regulators (miRDB)

36 targeting PRKAG1, 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-MIR-3064-3P	100.00	70.09	1254
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-4525	99.94	64.38	675
HSA-MIR-5010-5P	99.94	64.11	705
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-4530	99.69	66.47	1509
HSA-MIR-6513-3P	99.59	69.77	1102
HSA-MIR-4316	99.37	65.75	1360
HSA-MIR-145-3P	99.33	67.66	764
HSA-MIR-10522-5P	99.26	68.50	2087
HSA-MIR-296-3P	99.21	66.56	474
HSA-MIR-4478	99.07	65.16	2320
HSA-MIR-6749-3P	99.00	65.73	1443
HSA-MIR-1294	98.91	69.26	1030
HSA-MIR-9986	98.91	69.28	1024
HSA-MIR-4691-5P	98.41	66.77	1343
HSA-MIR-6792-3P	98.41	66.86	1359
HSA-MIR-3929	98.32	65.58	1026
HSA-MIR-4443	98.02	66.25	1928
HSA-MIR-6529-5P	97.85	66.47	673
HSA-MIR-4287	97.55	67.24	1247
HSA-MIR-4685-3P	97.55	67.35	1255
HSA-MIR-4286	97.20	64.37	1587

Literature-anchored findings (GeneRIF, showing 22)

• findings show that that a beta1(186-270)gamma1 complex can form in the absence of detectable alpha subunit and that beta1 Thr-263 and Tyr-267 are required for betagamma association but not alphabeta association (PMID:18079111)
• Inhibition of the KCa3.1 channels by AMP-activated protein kinase in human airway epithelial cells. (PMID:19052260)
• AMP-activated protein kinase inhibits alkaline pH- and PKA-induced apical vacuolar H+-ATPase accumulation in epididymal clear cells. (PMID:19211918)
• Results suggest that AMPK association with ULK1 plays an important role in autophagy induction. (PMID:21072212)
• Findings reveal that hypoxia can trigger AMPK activation in the apparent absence of increased [AMP] through ROS-dependent CRAC channel activation, leading to increases in cytosolic calcium that activate the AMPK upstream kinase CaMKKbeta. (PMID:21670147)
• Studies indicate that in most species, AMPK exists as an obligate heterotrimer, containing a catalytic subunit (alpha), and two regulatory subunits (beta and gamma). (PMID:21892142)
• In breast cancer cells SESN2 is associated with AMPK. (PMID:22363791)
• Conclude that cTnI phosphorylation by AMPK may represent a novel mechanism of regulation of cardiac function. (PMID:22456184)
• Data indicate that except AMPK-alpha1, expressions of the other five AMPK subunits -alpha2, -beta1, -beta2, -gamma1 and -gamma2 are significantly higher in ovarian carcinomas. (PMID:22897928)
• Studies suggest insights into the regulation of AMPK, its diverse biological actions, and therapeutic potential in the heart. (PMID:22935535)
• PRKAG1 interacts with DSCAM through its gamma subunit, and netrin-1 activates AMPK phosphorylation in cortical neurons. (PMID:23479427)
• Electrogenic phosphate transport in sodium/phosphate cotransporter NaPi-IIa-expressing Xenopus oocytes is markedly decreased by the coexpression of constitutively active AMPKgammaR70Q, but not of AMPK(alphaK45R). (PMID:24356547)
• Letter: report PRKAG1 frameshift mutations in colorectal cancer. (PMID:25267969)
• Pin1 plays an important role in the pathogenic mechanisms underlying impaired glucose and lipid metabolism, functioning as a negative regulator of AMPK (PMID:26276391)
• A subunit composition of AMPK (alpha2beta2gamma1) is preferred for colorectal cancer cell survival, at least in part, by stabilizing the tumor-specific expression of PGC1B. (PMID:26351140)
• Data suggest different gamma-isoforms in AMPK can have different effects on enzyme activation; here, activation of AMPK by compound 991 is greater if AMPK contains PRKAG2 versus PRKAG1 or PRKAG3. (PMID:28302767)
• AMP-activated protein kinase can be modulated by diverse ligands and by phosphorylation. (PMID:30206123)
• AMPK activity in response to redox changes is not due to direct action on AMPK itself, but is a secondary consequence of redox effects on other processes, such as mitochondrial ATP production. (PMID:30232152)
• DNA-dependent protein kinase regulates lysosomal AMP-dependent protein kinase activation and autophagy. (PMID:31983282)
• AMPK Complex Activation Promotes Sarcolemmal Repair in Dysferlinopathy. (PMID:32087766)
• The importance of the AMPK gamma 1 subunit in metformin suppression of liver glucose production. (PMID:32591547)
• S-nitrosylation of AMPKgamma impairs coronary collateral circulation and disrupts VSMC reprogramming. (PMID:38177907)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	prkag1	ENSDARG00000003818
mus_musculus	Prkag1	ENSMUSG00000067713
rattus_norvegicus	Prkag1	ENSRNOG00000070180
caenorhabditis_elegans		WBGENE00020633
caenorhabditis_elegans		WBGENE00021527

Paralogs (2): PRKAG2 (ENSG00000106617), PRKAG3 (ENSG00000115592)

Protein

Protein identifiers

5’-AMP-activated protein kinase subunit gamma-1 — P54619 (reviewed: P54619)

All UniProt accessions (13): P54619, F8VPF5, F8VQQ1, F8VRY2, F8VSH3, F8VSL2, F8VVA3, F8VYY9, F8VYZ8, F8VZX1, F8W046, H0YHF8, H0YIC9

UniProt curated annotations — full annotation on UniProt →

Function. AMP/ATP-binding subunit of AMP-activated protein kinase (AMPK), an energy sensor protein kinase that plays a key role in regulating cellular energy metabolism. In response to reduction of intracellular ATP levels, AMPK activates energy-producing pathways and inhibits energy-consuming processes: inhibits protein, carbohydrate and lipid biosynthesis, as well as cell growth and proliferation. AMPK acts via direct phosphorylation of metabolic enzymes, and by longer-term effects via phosphorylation of transcription regulators. Also acts as a regulator of cellular polarity by remodeling the actin cytoskeleton; probably by indirectly activating myosin. Gamma non-catalytic subunit mediates binding to AMP, ADP and ATP, leading to activate or inhibit AMPK: AMP-binding results in allosteric activation of alpha catalytic subunit (PRKAA1 or PRKAA2) both by inducing phosphorylation and preventing dephosphorylation of catalytic subunits. ADP also stimulates phosphorylation, without stimulating already phosphorylated catalytic subunit. ATP promotes dephosphorylation of catalytic subunit, rendering the AMPK enzyme inactive.

Subunit / interactions. AMPK is a heterotrimer of an alpha catalytic subunit (PRKAA1 or PRKAA2), a beta (PRKAB1 or PRKAB2) and a gamma non-catalytic subunits (PRKAG1, PRKAG2 or PRKAG3). Interacts with FNIP1 and FNIP2.

Post-translational modifications. Phosphorylated by ULK1 and ULK2; leading to negatively regulate AMPK activity and suggesting the existence of a regulatory feedback loop between ULK1, ULK2 and AMPK. Glycosylated; O-GlcNAcylated by OGT, promoting the AMP-activated protein kinase (AMPK) activity.

Domain organisation. The AMPK pseudosubstrate motif resembles the sequence around sites phosphorylated on target proteins of AMPK, except the presence of a non-phosphorylatable residue in place of Ser. In the absence of AMP this pseudosubstrate sequence may bind to the active site groove on the alpha subunit (PRKAA1 or PRKAA2), preventing phosphorylation by the upstream activating kinase STK11/LKB1. The 4 CBS domains mediate binding to nucleotides. Of the 4 potential nucleotide-binding sites, 3 are occupied, designated as sites 1, 3, and 4 based on the CBS modules that provide the acidic residue for coordination with the 2’- and 3’-hydroxyl groups of the ribose of AMP. Of these, site 4 appears to be a structural site that retains a tightly held AMP molecule (AMP 3). The 2 remaining sites, 1 and 3, can bind either AMP, ADP or ATP. Site 1 (AMP, ADP or ATP 1) is the high-affinity binding site and likely accommodates AMP or ADP. Site 3 (AMP, ADP or ATP 2) is the weakest nucleotide-binding site on the gamma subunit, yet it is exquisitely sensitive to changes in nucleotide levels and this allows AMPK to respond rapidly to changes in cellular energy status. Site 3 is likely to be responsible for protection of a conserved threonine in the activation loop of the alpha catalytic subunit through conformational changes induced by binding of AMP or ADP.

Miscellaneous. May be due to competing acceptor splice site.

Similarity. Belongs to the 5’-AMP-activated protein kinase gamma subunit family.

Isoforms (3)

UniProt ID	Names	Canonical?
P54619-1	1	yes
P54619-2	2
P54619-3	3

RefSeq proteins (3): NP_001193638, NP_001193639, NP_002724* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000644	CBS_dom	Domain
IPR046342	CBS_dom_sf	Homologous_superfamily
IPR050511	AMPK_gamma/SDS23_families	Family

Pfam: PF00571

Enzyme classification (BRENDA):

• EC 2.7.11.31 — [hydroxymethylglutaryl-CoA reductase (NADPH)] kinase (BRENDA: 25 organisms, 266 substrates, 134 inhibitors, 51 Km, 0 kcat entries)

Substrate kinetics (BRENDA)

19 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ATP	0.02–0.4168	15
BIOTIN-GGHMRSAMSGLHLVKRR-NH2	0.0267–0.1214	6
ACETYL-COA CARBOXYLASE	—	4
HMGSAMSGLHLVKRR	0.573–2.316	2
HMHSAMSGLHLVKRR	0.118–0.428	2
HMKSAMSGLHLVKRR	0.111–0.133	2
HMRSAGSGLHLVKRR	0.069–0.07	2
HMRSAMSGLHGVKRR	0.013–0.096	2
HMRSAMSGLHLGKRR	0.038–0.042	2
HMRSAMSGLHLVKRR	0.0498–0.091	2
HMRSAMTGLHGVKRR	0.034–0.065	2
HGRSAMSGLHLVKRR	0.0404	1
HISTONE	0.005	1
HISTONE H1	0.0029	1
HMRSAMSGLHGGKRR	0.049	1

UniProt features (89 total): binding site 35, helix 17, strand 16, domain 4, modified residue 3, mutagenesis site 3, turn 3, splice variant 2, sequence variant 2, chain 1, region of interest 1, short sequence motif 1, compositionally biased region 1

Structure

Experimental structures (PDB)

23 structures.

PDB	Method	Resolution (Å)
2UV4	X-RAY DIFFRACTION	1.33
2UV5	X-RAY DIFFRACTION	1.69
2UV6	X-RAY DIFFRACTION	2
2UV7	X-RAY DIFFRACTION	2
8BIK	X-RAY DIFFRACTION	2.5
5ISO	X-RAY DIFFRACTION	2.63
6C9H	X-RAY DIFFRACTION	2.65
6C9G	X-RAY DIFFRACTION	2.7
6B1U	X-RAY DIFFRACTION	2.77
6C9F	X-RAY DIFFRACTION	2.92
7MYJ	X-RAY DIFFRACTION	2.95
4ZHX	X-RAY DIFFRACTION	2.99
5EZV	X-RAY DIFFRACTION	2.99
4CFE	X-RAY DIFFRACTION	3.02
6C9J	X-RAY DIFFRACTION	3.05
7JHG	ELECTRON MICROSCOPY	3.47
6B2E	X-RAY DIFFRACTION	3.8
7JHH	ELECTRON MICROSCOPY	3.92
4CFF	X-RAY DIFFRACTION	3.92
7M74	ELECTRON MICROSCOPY	3.93
4RER	X-RAY DIFFRACTION	4.05
4REW	X-RAY DIFFRACTION	4.58
7JIJ	X-RAY DIFFRACTION	5.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P54619-F1	86.57	0.70

Antibody-complex structures (SAbDab): 3 — 7JHG, 7JHH, 7M74

Functional residue map

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

Ligand- & substrate-binding residues (35): 70; 70; 85–90; 85–90; 85–90; 130; 130; 130; 151–152; 151–152; 151–152; 151 …

Post-translational modifications (3): 261, 263, 270

Mutagenesis-validated functional residues (3):

Position	Phenotype
90	reduced amp-activation of phosphorylation of prkaa1 or prkaa2. reduced adp activation of phosphorylation of prkaa1 or pr
245	reduced amp-activation of phosphorylation of prkaa1 or prkaa2. reduced adp activation of phosphorylation of prkaa1 or pr
317	reduced amp-activation of phosphorylation of prkaa1 or prkaa2. does not affect adp activation of phosphorylation of prka

Function

Pathways and Gene Ontology

Reactome pathways

27 pathways

ID	Pathway
R-HSA-1445148	Translocation of SLC2A4 (GLUT4) to the plasma membrane
R-HSA-1632852	Macroautophagy
R-HSA-2151209	Activation of PPARGC1A (PGC-1alpha) by phosphorylation
R-HSA-380972	Energy dependent regulation of mTOR by LKB1-AMPK
R-HSA-5628897	TP53 Regulates Metabolic Genes
R-HSA-6804756	Regulation of TP53 Activity through Phosphorylation
R-HSA-9613354	Lipophagy
R-HSA-9619483	Activation of AMPK downstream of NMDARs
R-HSA-9931269	AMPK-induced ERAD and lysosome mediated degradation of PD-L1(CD274)
R-HSA-112314	Neurotransmitter receptors and postsynaptic signal transmission
R-HSA-112315	Transmission across Chemical Synapses
R-HSA-112316	Neuronal System
R-HSA-1592230	Mitochondrial biogenesis
R-HSA-162582	Signal Transduction
R-HSA-165159	MTOR signalling
R-HSA-1852241	Organelle biogenesis and maintenance
R-HSA-199991	Membrane Trafficking
R-HSA-212436	Generic Transcription Pathway
R-HSA-3700989	Transcriptional Regulation by TP53
R-HSA-438064	Post NMDA receptor activation events
R-HSA-442755	Activation of NMDA receptors and postsynaptic events
R-HSA-5633007	Regulation of TP53 Activity
R-HSA-5653656	Vesicle-mediated transport
R-HSA-73857	RNA Polymerase II Transcription
R-HSA-74160	Gene expression (Transcription)
R-HSA-9612973	Autophagy
R-HSA-9663891	Selective autophagy

MSigDB gene sets: 417 (showing top): MORF_MTA1, GOBP_NUCLEOSIDE_DIPHOSPHATE_METABOLIC_PROCESS, HNF3ALPHA_Q6, KEGG_ADIPOCYTOKINE_SIGNALING_PATHWAY, PAX4_01, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, SP3_Q3, BHATI_G2M_ARREST_BY_2METHOXYESTRADIOL_DN, GAUSSMANN_MLL_AF4_FUSION_TARGETS_C_UP, GOBP_CARBOHYDRATE_DERIVATIVE_CATABOLIC_PROCESS, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, MORF_HDAC2, FOXO4_01, GOBP_MALE_GAMETE_GENERATION, REACTOME_MEMBRANE_TRAFFICKING

GO Biological Process (13): regulation of glycolytic process (GO:0006110), protein phosphorylation (GO:0006468), fatty acid biosynthetic process (GO:0006633), signal transduction (GO:0007165), spermatogenesis (GO:0007283), cellular response to nutrient levels (GO:0031669), cellular response to glucose starvation (GO:0042149), regulation of carbon utilization (GO:0043609), positive regulation of gluconeogenesis (GO:0045722), import into nucleus (GO:0051170), regulation of cell cycle (GO:0051726), lipid metabolic process (GO:0006629), fatty acid metabolic process (GO:0006631)

GO Molecular Function (11): AMP-activated protein kinase activity (GO:0004679), cAMP-dependent protein kinase activity (GO:0004691), ATP binding (GO:0005524), cAMP-dependent protein kinase regulator activity (GO:0008603), AMP binding (GO:0016208), protein kinase regulator activity (GO:0019887), protein kinase binding (GO:0019901), ADP binding (GO:0043531), protein-containing complex binding (GO:0044877), nucleotide binding (GO:0000166), protein binding (GO:0005515)

GO Cellular Component (7): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), membrane (GO:0016020), nucleotide-activated protein kinase complex (GO:0031588), protein-containing complex (GO:0032991)

Reactome top-level categories

Rollup of top-17 pathways:

Category	Pathways
Membrane Trafficking	1
Autophagy	1
Mitochondrial biogenesis	1
MTOR signalling	1
Transcriptional Regulation by TP53	1
Regulation of TP53 Activity	1
Selective autophagy	1
Post NMDA receptor activation events	1
Regulation of PD-L1(CD274) Post-translational modification	1
Transmission across Chemical Synapses	1
Neuronal System	1
Organelle biogenesis and maintenance	1
Signal Transduction	1
Vesicle-mediated transport	1
RNA Polymerase II Transcription	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
adenyl ribonucleotide binding	3
regulation of cellular process	2
cellular response to stimulus	2
anion binding	2
binding	2
glycolytic process	1
regulation of purine nucleotide catabolic process	1
regulation of generation of precursor metabolites and energy	1
regulation of carbohydrate catabolic process	1
regulation of ATP metabolic process	1
phosphorylation	1
protein modification process	1
fatty acid metabolic process	1
lipid biosynthetic process	1
monocarboxylic acid biosynthetic process	1
cell communication	1
cellular process	1
signaling	1
developmental process involved in reproduction	1
male gamete generation	1
response to nutrient levels	1
cellular response to starvation	1
carbon utilization	1
regulation of response to nutrient levels	1
gluconeogenesis	1
regulation of gluconeogenesis	1
positive regulation of biosynthetic process	1
positive regulation of glucose metabolic process	1
nucleocytoplasmic transport	1
intercellular transport	1
cell cycle	1
primary metabolic process	1
lipid metabolic process	1
monocarboxylic acid metabolic process	1
protein serine/threonine kinase activity	1
AMP binding	1
cyclic nucleotide-dependent protein kinase activity	1
cAMP binding	1
purine ribonucleoside triphosphate binding	1

Protein interactions and networks

STRING

3008 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PRKAG1	PRKAB1	Q9Y478	998
PRKAG1	PRKAB2	O43741	996
PRKAG1	PRKAA1	Q13131	970
PRKAG1	PRKAA2	P54646	928
PRKAG1	H7C2H4	H7C2H4	815
PRKAG1	P0DN79	P0DN79	809
PRKAG1	FNIP1	Q8TF40	772
PRKAG1	FLCN	Q8NFG4	745
PRKAG1	FNIP2	Q9P278	656
PRKAG1	MTOR	P42345	645
PRKAG1	PRKAG3	Q9UGI9	582
PRKAG1	CAMKK2	Q96RR4	568
PRKAG1	STK11	Q15831	564
PRKAG1	TUFM	P49411	536
PRKAG1	GEMIN6	Q8WXD5	526

IntAct

236 interactions, top by confidence:

A	B	Type	Score
PRKAA1	PRKAB2	psi-mi:“MI:0914”(association)	0.950
PRKAB2	PRKAG1	psi-mi:“MI:0915”(physical association)	0.940
PRKAG1	PRKAA1	psi-mi:“MI:0915”(physical association)	0.940
PRKAG1	PRKAB2	psi-mi:“MI:0915”(physical association)	0.940
PRKAA1	PRKAG1	psi-mi:“MI:0915”(physical association)	0.940
PRKAA1	PRKAG1	psi-mi:“MI:0914”(association)	0.940
PRKAG1	PRKAA1	psi-mi:“MI:0914”(association)	0.940
PRKAG1	PRKAB2	psi-mi:“MI:0914”(association)	0.940
PRKAB2	PRKAG1	psi-mi:“MI:0914”(association)	0.940
PRKAG1	PRKAA2	psi-mi:“MI:0915”(physical association)	0.930
PRKAA2	PRKAG1	psi-mi:“MI:0915”(physical association)	0.930

BioGRID (267): PRKAG1 (Affinity Capture-Western), ACACA (Biochemical Activity), PRKAG1 (Two-hybrid), PRKAB1 (Two-hybrid), SNF1 (Two-hybrid), SIP1 (Two-hybrid), SIP2 (Two-hybrid), PRKAG1 (Reconstituted Complex), PRKAG1 (Reconstituted Complex), PRKAB1 (Reconstituted Complex), PRKAA1 (Reconstituted Complex), PRKAG1 (Reconstituted Complex), PRKAG1 (Affinity Capture-Western), PRKAB1 (Affinity Capture-Western), PRKAA1 (Affinity Capture-Western)

ESM2 similar proteins: A2RHP2, A5ISD9, A6QGF5, A6U173, A7N6S2, A7X1N2, A8Z3T5, B9DPG7, B9EBD5, E0SCY1, G2JZ44, O25337, O31698, O34921, O34994, O54950, P05033, P0A9H3, P0A9H4, P14175, P17328, P37599, P39066, P44717, P46920, P54619, P58108, P63843, P63844, P63845, P80385, Q032T5, Q09138, Q10343, Q2FHI3, Q2FZ27, Q2YXL3, Q49VI3, Q49X40, Q5HGH7

Diamond homologs: O54950, P12904, P54619, P58108, P80385, Q09138, Q10343, Q2LL38, Q54H97, Q5R4S0, Q8BGM7, Q8T277, Q91WG5, Q944A6, Q9MYP4, Q9P869, Q9UGI9, Q9UGJ0, Q58799, B1L5U5, O34682, O34921, O58045, O67820, P0C0H6, P0C0H7, P0DB88, P0DB89, P21879, P39066, P42851, P50100, P56088, P65168, P65169, P68839, P74081, P99106, P9WKI6, P9WKI7

SIGNOR signaling

8 interactions.

A	Effect	B	Mechanism
PRKAG1	“form complex”	AMPK	binding
PRKAG1	up-regulates	PRKAA2	binding
acadesine	up-regulates	PRKAG1	“chemical activation”
ADP	up-regulates	PRKAG1	“chemical activation”
ATP	down-regulates	PRKAG1	“chemical inhibition”
PRKDC	“up-regulates activity”	PRKAG1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 97 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
Energy dependent regulation of mTOR by LKB1-AMPK	6	34.2×	2e-06
Activation of AMPK downstream of NMDARs	6	33.1×	2e-06
MTOR signalling	6	23.1×	2e-05
Post NMDA receptor activation events	6	17.7×	6e-05
AMPK-induced ERAD and lysosome mediated degradation of PD-L1(CD274)	6	16.8×	7e-05
Activation of NMDA receptors and postsynaptic events	6	16.0×	8e-05
Macroautophagy	9	15.1×	2e-06
Autophagy	7	15.1×	2e-05

GO biological processes:

GO term	Partners	Fold	FDR
cellular response to nutrient levels	7	39.0×	3e-07
fatty acid biosynthetic process	5	20.9×	1e-03
positive regulation of autophagy	5	12.4×	9e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

1723 predictions. Top by Δscore:

Variant	Effect	Δscore
12:49003143:C:G	donor_loss	1.0000
12:49003143:CCT:C	donor_gain	1.0000
12:49003151:T:TA	donor_gain	1.0000
12:49003286:AGATT:A	acceptor_gain	1.0000
12:49003287:GATT:G	acceptor_gain	1.0000
12:49003288:ATT:A	acceptor_gain	1.0000
12:49003289:TT:T	acceptor_gain	1.0000
12:49003290:TC:T	acceptor_loss	1.0000
12:49003291:C:CA	acceptor_loss	1.0000
12:49003291:C:CC	acceptor_gain	1.0000
12:49003556:A:AC	donor_gain	1.0000
12:49003557:C:CC	donor_gain	1.0000
12:49003755:AC:A	donor_gain	1.0000
12:49003756:CC:C	donor_gain	1.0000
12:49003756:CCCTT:C	donor_gain	1.0000
12:49003918:GTGAT:G	acceptor_gain	1.0000
12:49003919:TGAT:T	acceptor_gain	1.0000
12:49003920:GAT:G	acceptor_gain	1.0000
12:49003920:GATC:G	acceptor_loss	1.0000
12:49003921:ATCT:A	acceptor_loss	1.0000
12:49003922:TCTGA:T	acceptor_loss	1.0000
12:49003923:C:CC	acceptor_gain	1.0000
12:49003923:CTGA:C	acceptor_loss	1.0000
12:49004505:A:AC	donor_gain	1.0000
12:49004506:C:CC	donor_gain	1.0000
12:49004506:CAA:C	donor_gain	1.0000
12:49004506:CAAA:C	donor_gain	1.0000
12:49004630:CAAG:C	acceptor_gain	1.0000
12:49005014:CACCT:C	acceptor_gain	1.0000
12:49005015:ACCT:A	acceptor_gain	1.0000

AlphaMissense

2154 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:49002948:G:A	S316F	1.000
12:49002963:C:T	G311E	1.000
12:49002964:C:G	G311R	1.000
12:49002964:C:T	G311R	1.000
12:49002996:A:G	L300P	1.000
12:49002999:C:G	R299P	1.000
12:49003003:G:C	H298D	1.000
12:49003195:G:C	C279W	1.000
12:49003197:A:G	C279R	1.000
12:49003286:A:G	L249P	1.000
12:49003565:T:A	D245V	1.000
12:49003565:T:C	D245G	1.000
12:49003567:A:C	F244L	1.000
12:49003567:A:T	F244L	1.000
12:49003569:A:G	F244L	1.000
12:49003570:C:A	K243N	1.000
12:49003570:C:G	K243N	1.000
12:49003774:G:C	P229R	1.000
12:49003774:G:T	P229Q	1.000
12:49003777:A:G	L228P	1.000
12:49003777:A:T	L228Q	1.000
12:49003780:G:T	A227D	1.000
12:49003864:C:T	G199D	1.000
12:49004519:G:C	F175L	1.000
12:49004519:G:T	F175L	1.000
12:49004521:A:G	F175L	1.000
12:49004526:A:G	L173P	1.000
12:49004532:C:G	R171P	1.000
12:49004534:C:A	K170N	1.000
12:49004534:C:G	K170N	1.000

dbSNP variants (sampled 300 via entrez): RS1000756521 (12:49016862 T>C), RS1000763192 (12:49006375 TA>T,TAA), RS1000817314 (12:49011959 A>G), RS1000848174 (12:49020022 T>A), RS1000908630 (12:49019620 T>C,G), RS1001088830 (12:49004158 G>A), RS1001245621 (12:49017881 C>T), RS1001317273 (12:49013804 G>A), RS1001376331 (12:49018797 C>G), RS1001435505 (12:49004548 T>C), RS1001964710 (12:49020080 A>C,T), RS1001982003 (12:49005691 G>A,C), RS1002031876 (12:49019140 G>A,C), RS1002251467 (12:49018930 A>G), RS1002495560 (12:49006349 G>A,C)

Disease associations

OMIM: gene MIM:602742 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST006021_11	Systolic blood pressure	4.000000e-10
GCST006022_9	Pulse pressure	3.000000e-08
GCST006611_106	HDL cholesterol	3.000000e-11
GCST007267_310	Systolic blood pressure	3.000000e-12
GCST008103_109	Bipolar disorder	4.000000e-06
GCST008129_63	Body mass index	4.000000e-12
GCST010988_491	Adult body size	9.000000e-09
GCST90002404_133	Red cell distribution width	5.000000e-09

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0006335	systolic blood pressure
EFO:0005763	pulse pressure measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004340	body mass index
EFO:0009188	Red cell distribution width

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (6): CHEMBL2096907 (PROTEIN COMPLEX GROUP), CHEMBL2111345 (PROTEIN COMPLEX), CHEMBL2393 (SINGLE PROTEIN), CHEMBL3038453 (PROTEIN COMPLEX), CHEMBL3038455 (PROTEIN COMPLEX), CHEMBL3038456 (PROTEIN COMPLEX)

Molecules with ChEMBL bioactivity

24 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 275,638 (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
CHEMBL752	ADENOSINE PHOSPHATE	4	165,316
CHEMBL2325741	CAPIVASERTIB	4	2,157
CHEMBL535	SUNITINIB	4	79,020
CHEMBL608533	MIDOSTAURIN	4	7,259
CHEMBL2105728	CRENOLANIB	3	2,167
CHEMBL3426621	RIPASUDIL	3	870
CHEMBL522892	DOVITINIB	3	4,944
CHEMBL603469	LESTAURTINIB	3
CHEMBL473659	GINSENOSIDE RD	3	1,735
CHEMBL3544911	PREXASERTIB	2	699
CHEMBL1230165	SILMITASERTIB	2	593
CHEMBL1236682	REFAMETINIB	2	3,223
CHEMBL402548	DANUSERTIB	2	1,928
CHEMBL482968	ENMD-2076	2	1,656
CHEMBL495727	AT-9283	2	1,376
CHEMBL575448	BMS-754807	2	406
CHEMBL3115681	NARAZACICLIB	2	287
CHEMBL3128043	PF-03758309	1	233
CHEMBL4169078	SRA-737	1	529
CHEMBL2041933	AZD-7762	1	1,240
CHEMBL3544932	TAK-901	1
CHEMBL3545085	XL-228	1
CHEMBL4289017	PF-03814735	1
CHEMBL482967	CYC-116	1

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — AMPK subfamily

Binding affinities (BindingDB)

318 measured of 322 human assays (322 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
4-[4-[2-[[(3R,3aR,6R,6aR)-3-hydroxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-6-yl]oxy]-6-chloro-1H-imidazo[4,5-b]pyridin-5-yl]phenyl]-N-[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]benzamide	EC50	0.05 nM	US-11407768: AMPK activators
4-[4-[2-[[(3R,3aR,6R,6aR)-3-hydroxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-6-yl]oxy]-6-chloro-1H-imidazo[4,5-b]pyridin-5-yl]phenyl]-N-[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]benzenesulfonamide	EC50	0.09 nM	US-11407768: AMPK activators
(2R,3R,4R,5S)-6-[[4-[4-[2-[[(3R,3aR,6R,6aR)-3-hydroxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-6-yl]oxy]-6-chloro-1H-imidazo[4,5-b]pyridin-5-yl]phenyl]phenyl]methylamino]hexane-1,2,3,4,5-pentol	EC50	0.1 nM	US-11407768: AMPK activators
(3R,3aR,6R,6aR)-6-[[6-chloro-5-[4-[2-hydroxy-4-[[2-(2-hydroxyethoxy)ethylamino]methyl]phenyl]phenyl]-1H-benzimidazol-2-yl]oxy]-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-3-ol	EC50	0.15 nM	US-11407768: AMPK activators
2-[[4-[4-[2-[[(3R,3aR,6R,6aR)-3-hydroxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-6-yl]oxy]-6-chloro-1H-imidazo[4,5-b]pyridin-5-yl]phenyl]phenyl]methylamino]-2-(hydroxymethyl)propane-1,3-diol	EC50	0.23 nM	US-11407768: AMPK activators
4-[4-[2-[[(3R,3aR,6R,6aR)-3-hydroxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-6-yl]oxy]-6-chloro-1H-benzimidazol-5-yl]phenyl]-3-hydroxy-N-[2-(2-hydroxyethoxy)ethyl]benzamide	EC50	0.37 nM	US-11407768: AMPK activators
5-[2-[[4-[4-[2-[[(3R,3aR,6R,6aR)-3-hydroxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-6-yl]oxy]-6-chloro-1H-imidazo[4,5-b]pyridin-5-yl]phenyl]benzoyl]amino]ethylamino]naphthalene-1-sulfonic acid	EC50	0.4 nM	US-11407768: AMPK activators
6-chloro-5-[4-[1-(hydroxymethyl)cyclopropyl]phenyl]-1H-indole-3-carboxylic acid	EC50	0.5 nM	US-9394285: Indole and indazole compounds that activate AMPK
3-[[4-[4-[2-[[(3R,3aR,6R,6aR)-3-hydroxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-6-yl]oxy]-6-chloro-1H-imidazo[4,5-b]pyridin-5-yl]phenyl]benzoyl]amino]propylphosphonic acid	EC50	0.5 nM	US-11407768: AMPK activators
2-[[4-[4-[2-[[(3R,3aR,6R,6aR)-3-hydroxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-6-yl]oxy]-6-chloro-1H-benzimidazol-5-yl]phenyl]benzoyl]amino]ethyl-trimethylazanium	EC50	0.56 nM	US-11407768: AMPK activators
(3R,3aR,6R,6aR)-6-[[5-[4-[4-[[4,4-bis(hydroxymethyl)piperidin-1-yl]methyl]phenyl]phenyl]-6-chloro-1H-imidazo[4,5-b]pyridin-2-yl]oxy]-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-3-ol	EC50	0.57 nM	US-11407768: AMPK activators
3-[[4-[4-[2-[[(3R,3aR,6R,6aR)-3-hydroxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-6-yl]oxy]-6-chloro-1H-imidazo[4,5-b]pyridin-5-yl]phenyl]benzoyl]amino]propane-1-sulfonic acid	EC50	0.62 nM	US-11407768: AMPK activators
3-[[4-[4-[2-[[(3R,3aR,6R,6aR)-3-hydroxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-6-yl]oxy]-6-chloro-1H-imidazo[4,5-b]pyridin-5-yl]phenyl]phenyl]methylamino]-2-hydroxypropanoic acid	EC50	0.63 nM	US-11407768: AMPK activators
4-[4-[2-[[(3R,3aR,6R,6aR)-3-hydroxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-6-yl]oxy]-6-chloro-1H-benzimidazol-5-yl]phenyl]-N-[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]benzenesulfonamide	EC50	0.63 nM	US-11407768: AMPK activators
4-[4-[2-[[(3R,3aR,6R,6aR)-3-hydroxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-6-yl]oxy]-6-chloro-1H-benzimidazol-5-yl]phenyl]-N-[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]benzamide	EC50	0.65 nM	US-11407768: AMPK activators
(3R,3aR,6R,6aR)-6-[[6-chloro-5-[4-[4-[[4-(2-hydroxyethyl)piperazin-1-yl]methyl]phenyl]phenyl]-1H-imidazo[4,5-b]pyridin-2-yl]oxy]-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-3-ol	EC50	0.72 nM	US-11407768: AMPK activators
US11407768, Compound 32	EC50	0.76 nM	US-11407768: AMPK activators
(2R,3R,4R,5S)-6-[[4-[4-[2-[[(3R,3aR,6R,6aR)-3-hydroxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-6-yl]oxy]-6-chloro-1H-benzimidazol-5-yl]phenyl]phenyl]methylamino]hexane-1,2,3,4,5-pentol	EC50	0.77 nM	US-11407768: AMPK activators
(3R,3aR,6R,6aR)-6-[[5-[4-[4-[[3,3-bis(hydroxymethyl)azetidin-1-yl]methyl]phenyl]phenyl]-6-chloro-1H-benzimidazol-2-yl]oxy]-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-3-ol	EC50	0.8 nM	US-11407768: AMPK activators
(3R,3aR,6R,6aR)-6-[[5-[4-[4-[[3,3-bis(hydroxymethyl)azetidin-1-yl]methyl]phenyl]phenyl]-6-chloro-1H-imidazo[4,5-b]pyridin-2-yl]oxy]-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-3-ol	EC50	0.81 nM	US-11407768: AMPK activators
2-[[4-[4-[2-[[(3R,3aR,6R,6aR)-3-hydroxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-6-yl]oxy]-6-chloro-1H-benzimidazol-5-yl]phenyl]phenyl]methylamino]-2-(hydroxymethyl)propane-1,3-diol	EC50	0.84 nM	US-11407768: AMPK activators
4-[4-[2-[[(3R,3aR,6R,6aR)-3-hydroxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-6-yl]oxy]-6-chloro-1H-benzimidazol-5-yl]phenyl]-N-[2-(2-hydroxyethoxy)ethyl]benzamide	EC50	0.85 nM	US-11407768: AMPK activators
(3R,3aR,6R,6aR)-6-[[5-[4-[4-[[4,4-bis(hydroxymethyl)piperidin-1-yl]methyl]phenyl]phenyl]-6-chloro-1H-benzimidazol-2-yl]oxy]-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-3-ol	EC50	0.85 nM	US-11407768: AMPK activators
2-[[4-[4-[2-[[(3R,3aR,6R,6aR)-3-hydroxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-6-yl]oxy]-6-chloro-1H-imidazo[4,5-b]pyridin-5-yl]phenyl]benzoyl]amino]ethanesulfonic acid	EC50	0.86 nM	US-11407768: AMPK activators
(3R,3aR,6R,6aR)-6-[[6-chloro-5-[4-[4-[(4-methylpiperazin-1-yl)methyl]phenyl]phenyl]-1H-benzimidazol-2-yl]oxy]-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-3-ol	EC50	0.89 nM	US-11407768: AMPK activators
(3R,3aR,6R,6aR)-6-[[6-chloro-5-[4-[4-[[4-(2-hydroxyethyl)piperazin-1-yl]methyl]phenyl]phenyl]-1H-benzimidazol-2-yl]oxy]-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-3-ol	EC50	0.93 nM	US-11407768: AMPK activators
(3R,3aR,6R,6aR)-6-[[6-chloro-5-[4-[4-[[2-(2-hydroxyethoxy)ethylamino]methyl]phenyl]phenyl]-1H-benzimidazol-2-yl]oxy]-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-3-ol	EC50	0.93 nM	US-11407768: AMPK activators
(3R,3aR,6R,6aR)-6-[[5-[4-[4-[[3-(aminomethyl)azetidin-1-yl]methyl]phenyl]phenyl]-6-chloro-1H-benzimidazol-2-yl]oxy]-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-3-ol	EC50	0.93 nM	US-11407768: AMPK activators
4-[4-[2-[[(3R,3aR,6R,6aR)-3-hydroxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-6-yl]oxy]-6-chloro-1H-benzimidazol-5-yl]phenyl]-N-[3-(4-aza-1-azoniabicyclo[2.2.2]octan-1-yl)propyl]benzamide	EC50	0.96 nM	US-11407768: AMPK activators
2-[4-[4-[2-[[(3R,3aR,6R,6aR)-3-hydroxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-6-yl]oxy]-6-chloro-1H-imidazo[4,5-b]pyridin-5-yl]phenyl]phenyl]-1H-1,2,4-triazol-5-one	EC50	1 nM	US-9290517: Azabenzimidazole hexahydrofuro[3,2-b]furan derivatives
(3R,3aR,6R,6aR)-6-[[6-chloro-5-[4-(4-morpholin-2-ylphenyl)phenyl]-1H-imidazo[4,5-b]pyridin-2-yl]oxy]-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-3-ol	EC50	1 nM	US-9290517: Azabenzimidazole hexahydrofuro[3,2-b]furan derivatives
2-[4-[4-[2-[[(3R,3aR,6R,6aR)-3-hydroxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-6-yl]oxy]-6-chloro-1H-imidazo[4,5-b]pyridin-5-yl]phenyl]phenyl]-1H-pyrazol-5-one	EC50	1 nM	US-9290517: Azabenzimidazole hexahydrofuro[3,2-b]furan derivatives
(3R)-1-[[4-[4-[2-[[(3R,3aR,6R,6aR)-3-hydroxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-6-yl]oxy]-6-chloro-1H-benzimidazol-5-yl]phenyl]phenyl]methyl]pyrrolidin-3-ol	EC50	1.04 nM	US-11407768: AMPK activators
2-[[4-[4-[2-[[(3R,3aR,6R,6aR)-3-hydroxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-6-yl]oxy]-6-chloro-1H-benzimidazol-5-yl]phenyl]phenyl]methylamino]propane-1,3-diol	EC50	1.08 nM	US-11407768: AMPK activators
(3R,3aR,6R,6aR)-6-[[6-chloro-5-[4-[4-[[3-(hydroxymethyl)azetidin-1-yl]methyl]phenyl]phenyl]-1H-benzimidazol-2-yl]oxy]-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-3-ol	EC50	1.09 nM	US-11407768: AMPK activators
4-[4-[2-[[(3R,3aR,6R,6aR)-3-hydroxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-6-yl]oxy]-6-chloro-1H-benzimidazol-5-yl]phenyl]-N-[2-(2-hydroxyethoxy)ethyl]-N-methylbenzamide	EC50	1.16 nM	US-11407768: AMPK activators
3-[[4-[4-[2-[[(3R,3aR,6R,6aR)-3-hydroxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-6-yl]oxy]-6-chloro-1H-imidazo[4,5-b]pyridin-5-yl]phenyl]benzoyl]amino]-2-(4-chlorophenyl)propane-1-sulfonic acid	EC50	1.22 nM	US-11407768: AMPK activators
(3R,3aR,6R,6aR)-6-[[6-chloro-5-[4-[4-[[2-(2-hydroxyethoxy)ethyl-methylamino]methyl]phenyl]phenyl]-1H-benzimidazol-2-yl]oxy]-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-3-ol	EC50	1.3 nM	US-11407768: AMPK activators
(2R,3R,4R,5S)-6-[1-[4-[4-[2-[[(3R,3aR,6R,6aR)-3-hydroxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-6-yl]oxy]-6-chloro-1H-imidazo[4,5-b]pyridin-5-yl]phenyl]phenyl]ethylamino]hexane-1,2,3,4,5-pentol	EC50	1.33 nM	US-11407768: AMPK activators
(3R,4S)-1-[[4-[4-[2-[[(3R,3aR,6R,6aR)-3-hydroxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-6-yl]oxy]-6-chloro-1H-benzimidazol-5-yl]phenyl]phenyl]methyl]pyrrolidine-3,4-diol	EC50	1.36 nM	US-11407768: AMPK activators
4-[4-[2-[[(3R,3aR,6R,6aR)-3-hydroxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-6-yl]oxy]-6-chloro-1H-benzimidazol-5-yl]phenyl]-N-[2-(2-hydroxyethoxy)ethyl]-N-methylbenzenesulfonamide	EC50	1.38 nM	US-11407768: AMPK activators
[4-[4-[2-[[(3R,3aR,6R,6aR)-3-hydroxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-6-yl]oxy]-6-chloro-1H-imidazo[4,5-b]pyridin-5-yl]phenyl]phenyl]phosphonic acid	EC50	1.4 nM	US-11407768: AMPK activators
(3S,4S)-1-[[4-[4-[2-[[(3R,3aR,6R,6aR)-3-hydroxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-6-yl]oxy]-6-chloro-1H-benzimidazol-5-yl]phenyl]phenyl]methyl]pyrrolidine-3,4-diol	EC50	1.4 nM	US-11407768: AMPK activators
(3R,3aR,6R,6aR)-6-[[6-chloro-5-[4-[4-[[3-(2-hydroxyethoxymethyl)azetidin-1-yl]methyl]phenyl]phenyl]-1H-benzimidazol-2-yl]oxy]-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-3-ol	EC50	1.46 nM	US-11407768: AMPK activators
4-[4-[2-[[(3R,3aR,6R,6aR)-3-hydroxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-6-yl]oxy]-6-chloro-1H-benzimidazol-5-yl]phenyl]-N-[2-(2-hydroxyethoxy)ethyl]benzenesulfonamide	EC50	1.51 nM	US-11407768: AMPK activators
2-[[4-[4-[2-[[(3R,3aR,6R,6aR)-3-hydroxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-6-yl]oxy]-6-chloro-1H-imidazo[4,5-b]pyridin-5-yl]phenyl]benzoyl]-(2-amino-2-oxoethyl)amino]ethanesulfonic acid	EC50	1.61 nM	US-11407768: AMPK activators
6-chloro-5-(4-phenylphenyl)-1H-indole-3-carboxylic acid	EC50	1.7 nM	US-9394285: Indole and indazole compounds that activate AMPK
US11407768, Compound 49	EC50	1.76 nM	US-11407768: AMPK activators
2-[[4-[4-[2-[[(3R,3aR,6R,6aR)-3-hydroxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-6-yl]oxy]-6-chloro-1H-imidazo[4,5-b]pyridin-5-yl]phenyl]benzoyl]-methylamino]ethanesulfonic acid	EC50	1.78 nM	US-11407768: AMPK activators
6-chloro-5-[4-(2-hydroxyphenyl)phenyl]-2,3,3a,4,5,6,7,7a-octahydro-1H-indazole-3-carboxylic acid	EC50	1.8 nM	US-9394285: Indole and indazole compounds that activate AMPK

ChEMBL bioactivities

705 potent at pChembl≥5 of 763 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.30	EC50	0.05	nM	CHEMBL6048763
10.05	EC50	0.09	nM	CHEMBL5810593
10.00	EC50	0.1	nM	CHEMBL5836835
9.82	EC50	0.15	nM	CHEMBL5892252
9.64	EC50	0.23	nM	CHEMBL5771550
9.43	EC50	0.37	nM	CHEMBL5796255
9.40	EC50	0.4	nM	CHEMBL6009640
9.34	EC50	0.46	nM	CHEMBL5783632
9.30	EC50	0.5	nM	CHEMBL3986249
9.30	EC50	0.5	nM	CHEMBL5891901
9.26	EC50	0.55	nM	CHEMBL6032116
9.25	EC50	0.56	nM	CHEMBL5775914
9.24	EC50	0.57	nM	CHEMBL5784714
9.22	EC50	0.6	nM	CHEMBL3393129
9.21	EC50	0.62	nM	CHEMBL5772530
9.20	EC50	0.63	nM	CHEMBL5894957
9.20	EC50	0.63	nM	CHEMBL5813619
9.19	EC50	0.65	nM	CHEMBL5881047
9.14	EC50	0.72	nM	CHEMBL5919560
9.12	EC50	0.76	nM	CHEMBL5825201
9.11	EC50	0.77	nM	CHEMBL5919095
9.10	EC50	0.8	nM	CHEMBL5919881
9.09	EC50	0.81	nM	CHEMBL5760186
9.08	EC50	0.84	nM	CHEMBL5992695
9.07	EC50	0.86	nM	CHEMBL5805427
9.07	EC50	0.85	nM	CHEMBL5967863
9.07	EC50	0.85	nM	CHEMBL5795930
9.05	EC50	0.89	nM	CHEMBL5770913
9.03	EC50	0.93	nM	CHEMBL5761917
9.03	EC50	0.93	nM	CHEMBL5930657
9.03	EC50	0.93	nM	CHEMBL5768406
9.02	EC50	0.96	nM	CHEMBL5983345
9.01	EC50	0.97	nM	CHEMBL5991168
9.00	EC50	1	nM	CHEMBL3393128
9.00	EC50	1	nM	CHEMBL3959081
9.00	EC50	1	nM	CHEMBL4108031
9.00	EC50	1	nM	CHEMBL4111083
9.00	EC50	1	nM	CHEMBL4110796
9.00	EC50	1	nM	CHEMBL4167177
9.00	EC50	1	nM	CHEMBL5179319
9.00	EC50	1	nM	CHEMBL5181529
9.00	EC50	1	nM	CHEMBL5183763
9.00	IC50	1	nM	CHEMBL5183579
9.00	IC50	1	nM	PF-03758309
8.98	EC50	1.04	nM	CHEMBL5754808
8.97	EC50	1.08	nM	CHEMBL5897987
8.96	EC50	1.1	nM	CHEMBL3393130
8.96	EC50	1.1	nM	CHEMBL5806531
8.96	EC50	1.09	nM	CHEMBL6058212
8.94	EC50	1.16	nM	CHEMBL5908554

PubChem BioAssay actives

374 with measured affinity, of 2325 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
[3-[[6-chloro-5-(1-methylindol-5-yl)-1H-benzimidazol-2-yl]oxy]phenyl]phosphonic acid	1189222: Activation of human AMPK alpha1beta1gamma1	ec50	0.0006	uM
5-[[6-chloro-5-[4-(2-hydroxyphenyl)phenyl]-1H-benzimidazol-2-yl]oxy]-2-methylbenzoic acid	1189222: Activation of human AMPK alpha1beta1gamma1	ec50	0.0010	uM
N-[(1S)-2-(dimethylamino)-1-phenylethyl]-6,6-dimethyl-3-[(2-methylthieno[3,2-d]pyrimidin-4-yl)amino]-1,4-dihydropyrrolo[3,4-d]pyrazole-5-carboxamide	2167998: Inhibition of human AMPK alpha1/beta1/gamma1 in presence of ATP	ic50	0.0010	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	1799383: in vitro Kinase Assay from Article 10.1021/cb9002865: “In vivo structure-activity relationship study of dorsomorphin analogues identifies selective VEGF and BMP inhibitors.”	ic50	0.0010	uM
N-[1-[(4-cyanophenyl)methyl]piperidin-4-yl]-5-[4-[(4-fluorophenyl)methyl]piperazine-1-carbonyl]pyridine-2-carboxamide	1855898: Activation of AMPK in human HepG2 cells assessed as increase in ACC phosphorylation at Ser79 incubated for 1 hr	ec50	0.0010	uM
5-[[6-chloro-5-(4-pyrrolidin-1-ylphenyl)-1H-imidazo[4,5-b]pyridin-2-yl]oxy]-2-methylbenzoic acid	1320682: Activation of full length human recombinant AMPK alpha1/beta1/gamma1 expressed in baculovirus infected sf21 cells using 5’-FAM-SAMS peptide substrate after 45 mins by fluorescence assay	ec50	0.0010	uM
N-[1-[(4-cyanophenyl)methyl]piperidin-4-yl]-5-[4-[fluoro-(4-fluorophenyl)methyl]piperidine-1-carbonyl]pyridine-2-carboxamide	1855899: Activation of AMPK in human HepG2 cells assessed as reduction in mitochondrial ATP production incubated for 1 hr	ic50	0.0010	uM
N-[1-[(4-cyanophenyl)methyl]piperidin-4-yl]-5-[4-[(4-fluorophenyl)methyl]-3,3-dimethylpiperazine-1-carbonyl]pyridine-2-carboxamide	1855898: Activation of AMPK in human HepG2 cells assessed as increase in ACC phosphorylation at Ser79 incubated for 1 hr	ec50	0.0010	uM
N-[1-[(4-cyanophenyl)methyl]piperidin-4-yl]-5-[4-[(4-methoxyphenyl)methyl]piperidine-1-carbonyl]pyridine-2-carboxamide	1855898: Activation of AMPK in human HepG2 cells assessed as increase in ACC phosphorylation at Ser79 incubated for 1 hr	ec50	0.0010	uM
(3R,3aR,6R,6aR)-6-[[6-chloro-5-(4-phenylphenyl)-1H-imidazo[4,5-b]pyridin-2-yl]oxy]-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-3-ol	1552802: Activation of recombinant human AMPK expressed in Sf9 cells using SAMS peptide as substrate preincubated for 30 mins followed by substrate addition and measured after 60 mins by fluorescence based assay	ec50	0.0010	uM
[2-[6-chloro-5-(4-pyrrolidin-1-ylphenyl)-1H-benzimidazol-2-yl]-5-methoxyphenyl]phosphonic acid	1189222: Activation of human AMPK alpha1beta1gamma1	ec50	0.0011	uM
[5-[[6-chloro-5-(4-morpholin-4-ylphenyl)-1H-benzimidazol-2-yl]oxy]-2-methylphenyl]phosphonic acid	1320681: Activation of full length human recombinant AMPK alpha1/beta1/gamma1 expressed in baculovirus infected sf21 cells using SAMS peptide substrate after 30 mins in presence of [33P]ATP by TopCount analysis	ec50	0.0012	uM
6-chloro-5-[4-(2-hydroxyphenyl)phenyl]-1H-indole-3-carboxylic acid	1315824: Activation of recombinant human AMPK alpha1/beta1/gamma1 using Cy5-labelled SAMS as substrate assessed as protection from Thr172 residue dephosphorylation preincubated for 15 mins followed by incubation with PP2a for 60 mins measured 60 mins post okadaic acid/Cy5-labelled SAMS and ATP addition by TR-FRET assay	ec50	0.0013	uM
6-chloro-5-[4-(1-hydroxycyclobutyl)phenyl]-1H-indole-3-carboxylic acid	1398174: Activation of full-length recombinant N-terminal His-tagged human AMPKalpha1beta1gamma1 expressed in Escherichia coli BL21 cells using Cy-5 SAMS peptide as substrate preincubated for 60 mins followed by substrate addition and measured after 60 mins in presence of PP2a by TR-FRET assay	ec50	0.0019	uM
2-[4-[2-[[(3R,3aR,6R,6aR)-3-hydroxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-6-yl]oxy]-6-chloro-1H-benzimidazol-5-yl]phenyl]benzene-1,3-diol	1320700: Activation of human recombinant AMPK alpha2/beta2/gamma1 expressed in African green monkey COS7 cells assessed as increase in biotinylated AAC (1 to 120 residues) peptide phosphorylation at Ser-79 residue measured after 60 mins by Alphascreen assay	ec50	0.0020	uM
5-[[6-chloro-5-(1-methylindol-5-yl)-1H-benzimidazol-2-yl]oxy]-2-methylbenzoic acid	1471575: Agonist activity at human recombinant phosphorylated AMPK complex 7 alpha2/beta1/gamma1 expressed in baculovirus infected Sf21 cells assessed as phosphorylation of 5-FAM-labeled SAMS substrate preincubated for 30 mins in presence of AMPK activator followed by substrate addition measured after 60 mins	ec50	0.0020	uM
N-[1-[(4-cyanophenyl)methyl]piperidin-4-yl]-5-[4-fluoro-4-(4-fluorobenzoyl)piperidine-1-carbonyl]pyridine-2-carboxamide	1855898: Activation of AMPK in human HepG2 cells assessed as increase in ACC phosphorylation at Ser79 incubated for 1 hr	ec50	0.0020	uM
N-[1-[(4-cyanophenyl)methyl]piperidin-4-yl]-5-[4-(4-fluorobenzoyl)piperidine-1-carbonyl]pyridine-2-carboxamide	1855898: Activation of AMPK in human HepG2 cells assessed as increase in ACC phosphorylation at Ser79 incubated for 1 hr	ec50	0.0020	uM
N-[1-[(4-cyanophenyl)methyl]piperidin-4-yl]-6-[4-(4-methoxybenzoyl)piperidine-1-carbonyl]pyridine-3-carboxamide	1855899: Activation of AMPK in human HepG2 cells assessed as reduction in mitochondrial ATP production incubated for 1 hr	ic50	0.0028	uM
N-[4-[4-[2-[[(3R,3aR,6R,6aR)-3-hydroxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-6-yl]oxy]-6-chloro-1H-imidazo[4,5-b]pyridin-5-yl]phenyl]-3-fluorophenyl]methanesulfonamide	1320693: Activation of full length human recombinant N-terminal GST-tagged AMPK alpha1/beta1/gamma1 expressed in baculovirus infected High Five cells using NH2-HMRSAMSGLHLVKRR CONH2 substrate after 60 mins by ADP-Glo kinase assay	ec50	0.0030	uM
5-[4-(4-cyanophenoxy)piperidine-1-carbonyl]-N-[1-[(4-cyanophenyl)methyl]piperidin-4-yl]pyridine-2-carboxamide	1855898: Activation of AMPK in human HepG2 cells assessed as increase in ACC phosphorylation at Ser79 incubated for 1 hr	ec50	0.0030	uM
(2R,3S,5R)-5-[[6-chloro-5-[4-(2-hydroxypropan-2-yl)phenyl]-1H-benzimidazol-2-yl]oxy]-2-(hydroxymethyl)oxan-3-ol	1320682: Activation of full length human recombinant AMPK alpha1/beta1/gamma1 expressed in baculovirus infected sf21 cells using 5’-FAM-SAMS peptide substrate after 45 mins by fluorescence assay	ec50	0.0040	uM
4-[[5-(1-cyclopropylindol-5-yl)-4,6-difluoro-1H-benzimidazol-2-yl]oxy]cyclohexane-1-carboxylic acid	1189222: Activation of human AMPK alpha1beta1gamma1	ec50	0.0040	uM
N-[1-[(4-cyanophenyl)methyl]piperidin-4-yl]-5-[4-(2,4-difluorophenoxy)piperidine-1-carbonyl]pyridine-2-carboxamide	1855898: Activation of AMPK in human HepG2 cells assessed as increase in ACC phosphorylation at Ser79 incubated for 1 hr	ec50	0.0040	uM
N-[4-[[(2-hydroxy-1H-indol-3-yl)-phenylmethylidene]amino]phenyl]-N-methyl-2-(4-methylpiperazin-1-yl)acetamide	1474638: Inhibition of AMPK (unknown origin) using SAMS peptide as substrate measured after 30 mins in presence of [gamma32P]ATP by liquid scintillation counting method	ki	0.0042	uM
[4-[5-[1-[(6-methoxy-3-pyridinyl)methyl]piperidin-4-yl]-1,3,4-oxadiazol-2-yl]phenyl]-[4-[[4-(trifluoromethyl)phenyl]methyl]piperazin-1-yl]methanone;bis(4-methylbenzenesulfonic acid)	1666796: Activation of AMPK in human MDA-MB-435 cells measured after 2 hrs by anti-phospho-Acetyl-CoA Carboxylase (Ser79) antibody-based ELISA	ec50	0.0045	uM
N-[(1R,2S)-2-aminocyclohexyl]-4-[6-(1-methylpyrazol-4-yl)pyrazolo[1,5-a]pyrimidin-3-yl]thiophene-2-carboxamide	1637052: Inhibition of full-length recombinant human GST and His-tagged AMPK alpha1/beta1/gamma1 expressed in baculovirus expression system by LanthaScreen assay	ic50	0.0046	uM
4-[(4-methoxyphenyl)methyl]-N-[4-[4-[[4-(trifluoromethyl)phenyl]methyl]piperazine-1-carbonyl]phenyl]piperazine-1-carboxamide	1666796: Activation of AMPK in human MDA-MB-435 cells measured after 2 hrs by anti-phospho-Acetyl-CoA Carboxylase (Ser79) antibody-based ELISA	ec50	0.0047	uM
2-hydroxy-3-[N-[4-[methyl-[2-(4-methylpiperazin-1-yl)acetyl]amino]phenyl]-C-phenylcarbonimidoyl]-1H-indole-5-carboxylic acid	1474638: Inhibition of AMPK (unknown origin) using SAMS peptide as substrate measured after 30 mins in presence of [gamma32P]ATP by liquid scintillation counting method	ki	0.0049	uM
5-[4-(4-cyanobenzoyl)piperidine-1-carbonyl]-N-[1-[(4-cyanophenyl)methyl]piperidin-4-yl]pyridine-2-carboxamide	1855898: Activation of AMPK in human HepG2 cells assessed as increase in ACC phosphorylation at Ser79 incubated for 1 hr	ec50	0.0050	uM
4-[4-[2-[[(3R,3aR,6R,6aR)-3-hydroxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-6-yl]oxy]-6-chloro-1H-imidazo[4,5-b]pyridin-5-yl]phenyl]-3-fluorobenzonitrile	1320688: Activation of full length human recombinant AMPK alpha2/beta1/gamma1 expressed in baculovirus infected sf21 cells using 5’-FAM-SAMS peptide substrate after 45 mins by fluorescence assay	ec50	0.0050	uM
4,6-difluoro-5-[4-[(2S)-oxan-2-yl]phenyl]-1H-indole-3-carboxylic acid	1398173: Activation of full-length recombinant N-terminal His-tagged human AMPKalpha2beta1gamma1 expressed in Escherichia coli BL21 cells using Cy-5 SAMS peptide as substrate preincubated for 60 mins followed by substrate addition and measured after 60 mins in presence of PP2a by TR-FRET assay	ec50	0.0060	uM
N-[1-[(4-cyanophenyl)methyl]piperidin-4-yl]-5-[4-[2-(4-fluorophenyl)propan-2-yl]piperazine-1-carbonyl]pyridine-2-carboxamide	1855898: Activation of AMPK in human HepG2 cells assessed as increase in ACC phosphorylation at Ser79 incubated for 1 hr	ec50	0.0060	uM
bis(N-cyclohexylcyclohexanamine);[5-(5-oxo-2H-1,2-oxazol-3-yl)furan-2-yl]phosphonic acid	580978: Activation of human AMPK after 15 mins	ec50	0.0063	uM
5-[[5-chloro-6-(2-phenylethynyl)-1H-benzimidazol-2-yl]oxy]-2-methylbenzoic acid	1471575: Agonist activity at human recombinant phosphorylated AMPK complex 7 alpha2/beta1/gamma1 expressed in baculovirus infected Sf21 cells assessed as phosphorylation of 5-FAM-labeled SAMS substrate preincubated for 30 mins in presence of AMPK activator followed by substrate addition measured after 60 mins	ec50	0.0070	uM
6-chloro-5-[6-(dimethylamino)-2-methoxy-3-pyridinyl]-1H-indole-3-carboxylic acid	1398174: Activation of full-length recombinant N-terminal His-tagged human AMPKalpha1beta1gamma1 expressed in Escherichia coli BL21 cells using Cy-5 SAMS peptide as substrate preincubated for 60 mins followed by substrate addition and measured after 60 mins in presence of PP2a by TR-FRET assay	ec50	0.0070	uM
4-[[4-(trifluoromethyl)phenyl]methyl]-N-[4-[4-[[4-(trifluoromethyl)phenyl]methyl]piperazine-1-carbonyl]phenyl]piperazine-1-carboxamide	1666796: Activation of AMPK in human MDA-MB-435 cells measured after 2 hrs by anti-phospho-Acetyl-CoA Carboxylase (Ser79) antibody-based ELISA	ec50	0.0079	uM
5-[[6-chloro-5-(4-phenylphenyl)-1H-benzimidazol-2-yl]oxy]-2-methylbenzoic acid	1471575: Agonist activity at human recombinant phosphorylated AMPK complex 7 alpha2/beta1/gamma1 expressed in baculovirus infected Sf21 cells assessed as phosphorylation of 5-FAM-labeled SAMS substrate preincubated for 30 mins in presence of AMPK activator followed by substrate addition measured after 60 mins	ec50	0.0080	uM
N-[1-[(4-cyanophenyl)methyl]piperidin-4-yl]-5-[4-(2,4-difluorobenzoyl)piperidine-1-carbonyl]pyridine-2-carboxamide	1855899: Activation of AMPK in human HepG2 cells assessed as reduction in mitochondrial ATP production incubated for 1 hr	ic50	0.0080	uM
6-chloro-5-[4-(1-hydroxycyclobutyl)phenyl]-1H-indazole-3-carboxylic acid	1320672: Activation of full length human phosphorylated His-tagged AMPK alpha1/beta1/gamma1 expressed in Escherichia coli BL21-CodonPlus (DE3)-RIPL using SAMS peptide substrate preincubated for 15 mins followed by PP2A addition for 90 mins followed by substrate addition measured after 60 mins in presence of [33P]ATP by scintillation counting method	ec50	0.0083	uM
6-[4-(4-methoxybenzoyl)piperidine-1-carbonyl]-N-[1-[[4-(trifluoromethoxy)phenyl]methyl]piperidin-4-yl]pyridine-3-carboxamide	1855898: Activation of AMPK in human HepG2 cells assessed as increase in ACC phosphorylation at Ser79 incubated for 1 hr	ec50	0.0090	uM
6-[4-(4-pyrrolidin-1-ylbenzoyl)piperidine-1-carbonyl]-N-[1-[[4-(trifluoromethoxy)phenyl]methyl]piperidin-4-yl]pyridine-3-carboxamide	1855898: Activation of AMPK in human HepG2 cells assessed as increase in ACC phosphorylation at Ser79 incubated for 1 hr	ec50	0.0090	uM
methyl 2-hydroxy-3-[N-[4-[methyl-[2-(4-methylpiperazin-1-yl)acetyl]amino]phenyl]-C-phenylcarbonimidoyl]-1H-indole-5-carboxylate	1474638: Inhibition of AMPK (unknown origin) using SAMS peptide as substrate measured after 30 mins in presence of [gamma32P]ATP by liquid scintillation counting method	ki	0.0092	uM
4-[6-[4-(2-piperidin-1-ylethoxy)phenyl]pyrazolo[1,5-a]pyrimidin-3-yl]-N-(2,2,2-trifluoroethyl)thiophene-2-carboxamide	1637052: Inhibition of full-length recombinant human GST and His-tagged AMPK alpha1/beta1/gamma1 expressed in baculovirus expression system by LanthaScreen assay	ic50	0.0100	uM
1-[(4-methoxyphenyl)methyl]-N-[4-[4-[[4-(trifluoromethyl)phenyl]methyl]piperazine-1-carbonyl]phenyl]piperidine-4-carboxamide;dihydrochloride	1666796: Activation of AMPK in human MDA-MB-435 cells measured after 2 hrs by anti-phospho-Acetyl-CoA Carboxylase (Ser79) antibody-based ELISA	ec50	0.0110	uM
N-[1-[(4-cyanophenyl)methyl]piperidin-4-yl]-5-[4-(4-methoxyphenoxy)piperidine-1-carbonyl]pyridine-2-carboxamide	1855898: Activation of AMPK in human HepG2 cells assessed as increase in ACC phosphorylation at Ser79 incubated for 1 hr	ec50	0.0110	uM
5-[[6-chloro-5-[4-(1H-pyrazol-5-yl)phenyl]-1H-benzimidazol-2-yl]oxy]-2-methylbenzoic acid	1471575: Agonist activity at human recombinant phosphorylated AMPK complex 7 alpha2/beta1/gamma1 expressed in baculovirus infected Sf21 cells assessed as phosphorylation of 5-FAM-labeled SAMS substrate preincubated for 30 mins in presence of AMPK activator followed by substrate addition measured after 60 mins	ec50	0.0110	uM
1-[(6-methoxy-3-pyridinyl)methyl]-N-[4-[4-[[4-(trifluoromethyl)phenyl]methyl]piperazine-1-carbonyl]phenyl]piperidine-4-carboxamide	1666796: Activation of AMPK in human MDA-MB-435 cells measured after 2 hrs by anti-phospho-Acetyl-CoA Carboxylase (Ser79) antibody-based ELISA	ec50	0.0120	uM
N-[1-[(4-fluorophenyl)methyl]piperidin-4-yl]-6-[4-(4-pyrrolidin-1-ylbenzoyl)piperidine-1-carbonyl]pyridine-3-carboxamide	1855898: Activation of AMPK in human HepG2 cells assessed as increase in ACC phosphorylation at Ser79 incubated for 1 hr	ec50	0.0120	uM
3-(2,2-difluoro-10,12-dimethyl-1-aza-3-azonia-2-boranuidatricyclo[7.3.0.03,7]dodeca-3,5,7,9,11-pentaen-4-yl)-N-[2-[2-[2-[2-[[(2S,3R,4R,6R)-3-methoxy-2-methyl-16-oxo-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-4-yl]amino]ethoxy]ethoxy]ethoxy]ethyl]propanamide	1526218: Binding affinity to recombinant human full-length GST N-Terminal tagged-AMPK alpha1/N-Terminal GST tagged-AMPK beta1/N-Terminal his-tagged AMPK gamma1 expressed in baculovirus expression system incubated for 1 hr by TR-FRET assay	kd	0.0130	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol F	increases expression, affects cotreatment, decreases expression	2
bisphenol A	decreases expression	2
Arsenic	affects methylation, affects cotreatment, increases abundance, increases expression	2
Doxorubicin	affects expression, decreases expression	2
aristolochic acid I	decreases expression	1
moringin	affects cotreatment, increases expression	1
TAK-243	increases sumoylation	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases expression, increases abundance	1
decabromobiphenyl ether	decreases expression	1
beta-lapachone	increases expression	1
arsenite	affects binding, increases reaction	1
sodium arsenite	affects cotreatment, increases abundance, increases expression	1
tetrabromobisphenol A	decreases expression	1
methacrylaldehyde	increases abundance, affects cotreatment, increases expression	1
cordycepin	affects binding	1
di-n-butylphosphoric acid	affects expression	1
azoxystrobin	decreases expression	1
CGP 52608	affects binding, increases reaction	1
K 7174	increases expression	1
fenpyroximate	decreases expression	1
4-chloro-N-((4-(1,1-dimethylethyl)phenyl)methyl)-3-ethyl-1-methyl-1H-pyrazole-5-carboxamide	decreases expression	1
ICG 001	decreases expression	1
bisphenol B	increases expression	1
pyrachlostrobin	decreases expression	1
picoxystrobin	decreases expression	1
bisphenol AF	increases expression	1
Decitabine	increases expression	1
Acrolein	affects cotreatment, increases expression, increases abundance	1

ChEMBL screening assays

482 unique, capped per target: 481 binding, 1 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1053698	Binding	Induction of AMPK phosphorylation in human HepG2 cells by Western blot analysis in presence of 33 mM glucose	Palbinone and triterpenes from Moutan Cortex (Paeonia suffruticosa, Paeoniaceae) stimulate glucose uptake and glycogen synthesis via activation of AMPK in insulin-resistant human HepG2 Cells. — Bioorg Med Chem Lett
CHEMBL4649950	Functional	AMP-dependent Kinase enzyme assay. An in vitro enzyme assay that detects ADP turnover that is directly proportional to AMPK activity. This uses naive AMPK that is activated during the assay with MK-8722	University of Dundee, Small-Polar-MMV Screening Library

Cellosaurus cell lines

12 cell lines: 11 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D1Q4	Abcam K-562 PRKAG1 KO	Cancer cell line	Female
CVCL_D2LQ	Abcam Raji PRKAG1 KO	Cancer cell line	Male
CVCL_D7YF	Ubigene A-549 PRKAG1 KO	Cancer cell line	Male
CVCL_D8TV	Ubigene HCT 116 PRKAG1 KO	Cancer cell line	Male
CVCL_D9PI	Ubigene HEK293 PRKAG1 KO	Transformed cell line	Female
CVCL_E0LT	Ubigene HeLa PRKAG1 KO	Cancer cell line	Female
CVCL_E1L6	HyCyte Hep-G2 KO-hPRKAG1	Cancer cell line	Male
CVCL_TG74	HAP1 PRKAG1 (-) 1	Cancer cell line	Male
CVCL_TG75	HAP1 PRKAG1 (-) 2	Cancer cell line	Male
CVCL_TG76	HAP1 PRKAG1 (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

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