PRKAB1

Summary

PRKAB1 (protein kinase AMP-activated non-catalytic subunit beta 1, HGNC:9378) is a protein-coding gene on chromosome 12q24.23, encoding 5’-AMP-activated protein kinase subunit beta-1 (Q9Y478). Non-catalytic 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 may be a positive regulator of AMPK activity. The myristoylation and phosphorylation of this subunit have been shown to affect the enzyme activity and cellular localization of AMPK. This subunit may also serve as an adaptor molecule mediating the association of the AMPK complex.

Source: NCBI Gene 5564 — RefSeq curated summary.

At a glance

• GWAS associations: 9
• Clinical variants (ClinVar): 34 total
• Druggable target: yes — 5 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_006253

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9378
Approved symbol	PRKAB1
Name	protein kinase AMP-activated non-catalytic subunit beta 1
Location	12q24.23
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000111725
Ensembl biotype	protein_coding
OMIM	602740
Entrez	5564

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 5 protein_coding, 3 retained_intron, 1 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000229328, ENST00000537057, ENST00000537400, ENST00000538271, ENST00000540121, ENST00000541640, ENST00000542698, ENST00000545223, ENST00000545870, ENST00000630317

RefSeq mRNA: 1 — MANE Select: NM_006253 NM_006253

CCDS: CCDS9191

Canonical transcript exons

ENST00000229328 — 7 exons

Exon	Start	End
ENSE00001132347	119668133	119668403
ENSE00002249689	119680248	119681619
ENSE00003492665	119676537	119676670
ENSE00003519467	119674340	119674454
ENSE00003530717	119673964	119674057
ENSE00003604293	119679933	119680001
ENSE00003667286	119672301	119672464

Expression profiles

Bgee: expression breadth ubiquitous, 254 present calls, max score 96.04.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 27.5969 / max 433.3324, expressed in 1812 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
128303	22.6578	1807
128304	2.4617	1152
128302	1.8787	1089
128305	0.5987	275

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
metanephros cortex	UBERON:0010533	96.04	gold quality
rectum	UBERON:0001052	95.44	gold quality
mucosa of transverse colon	UBERON:0004991	95.32	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	94.49	gold quality
transverse colon	UBERON:0001157	94.37	gold quality
adult mammalian kidney	UBERON:0000082	94.35	gold quality
body of stomach	UBERON:0001161	94.28	gold quality
lower esophagus mucosa	UBERON:0035834	93.85	gold quality
small intestine Peyer’s patch	UBERON:0003454	93.13	gold quality
stomach	UBERON:0000945	93.06	gold quality
kidney	UBERON:0002113	92.44	gold quality
spleen	UBERON:0002106	92.28	gold quality
renal medulla	UBERON:0000362	92.22	gold quality
small intestine	UBERON:0002108	92.15	gold quality
upper lobe of left lung	UBERON:0008952	91.91	gold quality
body of pancreas	UBERON:0001150	91.84	gold quality
adult organism	UBERON:0007023	91.70	gold quality
intestine	UBERON:0000160	91.16	gold quality
colon	UBERON:0001155	91.12	gold quality
esophagus mucosa	UBERON:0002469	91.04	gold quality
right lung	UBERON:0002167	91.02	gold quality
cortex of kidney	UBERON:0001225	90.98	gold quality
large intestine	UBERON:0000059	90.94	gold quality
upper lobe of lung	UBERON:0008948	90.91	gold quality
esophagus	UBERON:0001043	90.62	gold quality
right adrenal gland cortex	UBERON:0035827	90.61	gold quality
minor salivary gland	UBERON:0001830	90.54	gold quality
colonic epithelium	UBERON:0000397	90.50	gold quality
left adrenal gland	UBERON:0001234	90.45	gold quality
nephron tubule	UBERON:0001231	90.42	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	16.21
E-MTAB-6678	no	3.49

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

2 targets.

Target	Regulation
FLCN	Activation
FNIP1	Activation

Upstream regulators (CollecTRI, top): TP53

miRNA regulators (miRDB)

62 targeting PRKAB1, 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-574-5P	100.00	66.01	989
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-3912-5P	99.95	66.11	925
HSA-MIR-9718	99.94	68.91	918
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-4671-3P	99.88	72.46	1045
HSA-MIR-137-3P	99.87	74.74	2401
HSA-MIR-8067	99.86	69.59	2260
HSA-MIR-6842-5P	99.80	67.54	1587
HSA-MIR-7110-5P	99.80	67.84	1712
HSA-MIR-2052	99.79	69.37	2031
HSA-MIR-4645-3P	99.76	69.33	993
HSA-MIR-4719	99.73	72.10	3329
HSA-MIR-1179	99.71	68.70	1040
HSA-MIR-1208	99.70	68.28	1533
HSA-MIR-5093	99.67	69.26	2291
HSA-MIR-561-3P	99.64	70.90	3647
HSA-MIR-875-3P	99.63	69.47	2548
HSA-MIR-4663	99.62	65.33	957
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-6752-5P	99.59	67.32	1243
HSA-MIR-12122	99.56	69.33	1672
HSA-MIR-1252-3P	99.55	67.71	2862
HSA-MIR-510-3P	99.54	70.06	2965
HSA-MIR-3120-3P	99.54	70.28	2669
HSA-MIR-4761-5P	99.51	66.69	804

Literature-anchored findings (GeneRIF, showing 40)

• AMP-activated protein kinase has a role in gene expression in single islet beta-cells [review] (PMID:15289653)
• Dipyridamole, an adenosine transporter inhibitor, and 5’-amino-5’-deoxyadenosine, an adenosine kinase inhibitor, blocked the effect of AICAR on the down-regulation of the insulin receptor protein, mRNA, and promoter activity. (PMID:15694368)
• Reduced activation of AMPK by globular adiponectin in obese and obese type 2 diabetic subjects is not caused by reduced adiponectin receptor expression. (PMID:15769985)
• it is likely that the AMPK-GDE association is a novel mechanism regulating AMPK activity and the resultant fatty acid oxidation and glucose uptake (PMID:15886229)
• These results suggested that the combination of 5-FU and genistein exert a novel chemotherapeutic effect in colon cancers, and AMPK may be a regulatory molecule of COX-2 expression, further implying its involvement in cytotoxicity caused by genistein. (PMID:15896711)
• These are the first data to show an effect of AMPK on cell movement, and suggest a fundamental role for energy deficiency in regulating cellular behaviour. (PMID:16405649)
• These results show that AICAR and insulin/IGF-1 regulate VEGF expression through different mechanisms. (PMID:16516166)
• In conclusion, during prolonged submaximal exercise at 60% VO2peak, higher fat oxidation in women cannot be explained by higher AMPK signalling. (PMID:16600998)
• AMPK phosphorylated TRIP6 in vitro at the N-terminus and the transcriptional co-activator properties of TRIP6 were enhanced by AMPK action. (PMID:16624523)
• AMPK activation and a reduced phosphorylation of 4E-BP1 may contribute to the inhibition of muscle protein synthesis during resistance exercise. (PMID:16873412)
• Endothelial cells possess two pathways to activate AMPK, one Ca2+/CaMKKbeta dependent and one AMP/LKB1 dependent. (PMID:16880506)
• AMPK has a role in regulating growth of cultured human keratinocytes (PMID:16949049)
• modulation of AMPK activity did not affect PI3K/AKT signalling, an advantage for the potential use of AMPK as a target for cancer therapy in LKB1 wild-type tumours (PMID:16953221)
• analysis of a new model for AMPK heterotrimer structure where through its C terminus the beta-subunit binds to the alpha-subunit that, in turn, binds to the gamma-subunit (PMID:17012231)
• Results suggest that FLCN, mutated in Birt-Hogg-Dube syndrome, and its interacting partner FNIP1 may be involved in energy and/or nutrient sensing through the AMPK and mTOR signaling pathways. (PMID:17028174)
• These findings suggest that the activation of JAK2, but not STAT3, may play a critical role in leptin-induced AMPK activation in Huh7 cells. (PMID:17054914)
• AMPK mediates IL-2 production by regulating NF-AT and AP-1activation during T cell stimulation. (PMID:17097050)
• phosphatidylinositol 3-kinase/Akt signaling and induces apoptosis is inhibited by energy depletion via AMP-activated protein kinase-dependent phosphorylation of IRS-1 at Ser-794 (PMID:17459875)
• 5-Aminoimidazole-4-carboxamide riboside sensitizes TRAIL- and TNF{alpha}-induced cytotoxicity in colon cancer cells through AMP-activated protein kinase signaling (PMID:17513605)
• These results suggest that activation of AMPK inhibits multiple myeloma (MM) cell growth despite stimulation with IL-6, IGF-1, or HS-5 stromal cell conditioned medium and represents a potential new target in the therapy of MM. (PMID:17669398)
• regulation of FOXO3 by AMPK may play a crucial role in fine tuning gene expression programs that control energy balance and stress resistance in cells throughout life (PMID:17711846)
• Grb2 functions as a factor which mediates phosphorylation of AMPK at Thr172. (PMID:17849173)
• AMPK activated by fluid shear stress is a novel regulator of FoxO1a phosphorylation and protein levels. (PMID:18006475)
• metformin-mediated AMPK activation leads to inhibition of mTOR and a reduction in translation initiation (PMID:18006825)
• 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 SIRT1 in telomerase-immortalized human cells and hematopoietic stem cells obtained from SIRT1-deficient mice enhanced cell growth under normal and nutrient limiting conditions. (PMID:18184747)
• AMP-activated protein kinase (AMPK) regulates GLUT4 transcription through the histone deacetylase (HDAC)5 transcriptional repressor. (PMID:18184930)
• the activities of AMP-activated protein kinase, protein kinase B, and mammalian target of rapamycin by limiting energy availability with 2-deoxyglucose (PMID:18247380)
• AMPK inhibits TGFbeta-induced transcription downstream of Smad3 COOH-terminal phosphorylation and nuclear translocation (PMID:18250161)
• AMPK activity is a key determinant of HIF-1 functions in response to reactive oxygen species and may be involffed in HIF-1 regulatory mechanisms. (PMID:18258605)
• AMPK regulates the proteasomal activity under conditions of energy demand. (PMID:18328803)
• modulating basal AMPK and CAMKKB activity in the hypothalamus is essential for maintaining tight regulation of pathways contributing to food intake (PMID:18436530)
• UVB irradfiation regulates COX2 mRNA stability through AMPK and HuR in human keratinocytes. (PMID:18449856)
• Results report that oxygen deprivation can activate the autophagic pathway in human cancer cell lines via AMPK activity, independent of HIF-1, BNIP3, and BNIP3L. (PMID:18551130)
• Data suggest that increased expression of malonyl CoA decarboxylase, and the decreased expression of acetyl CoA carboxylase and 5’-AMP activated protein kinase are important regulators of the maturation of fatty acid oxidation in the newborn human heart. (PMID:18614968)
• Akt and AMPK have roles in the pathway of hydrogen peroxide-activated endothelial nitric-oxide synthase phosphorylation and function (PMID:18617528)
• The proliferation potential of senescent human diploid fibroblasts can be modulated through the regulation of the AMPK signaling pathway. (PMID:18729810)
• AMPK controls the molecular mechanism underlying the differential biological functions of JNK, providing a novel explanation for the antiapoptotic role of LKB1. (PMID:19037093)
• Regulation of erythrocyte survival by AMPK is reported. (PMID:19050047)
• These findings raise the possibility that glucose-induced changes in AMPK are linked to alterations in SIRT1 abundance and activity and possibly cellular redox state. (PMID:19071085)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	prkab1a	ENSDARG00000044183
danio_rerio	prkab1b	ENSDARG00000046143
mus_musculus	Prkab1	ENSMUSG00000029513
rattus_norvegicus	Prkab1	ENSRNOG00000001142
drosophila_melanogaster	alc	FBGN0260972
caenorhabditis_elegans		WBGENE00007222
caenorhabditis_elegans		WBGENE00010115
caenorhabditis_elegans		WBGENE00012928

Paralogs (1): PRKAB2 (ENSG00000131791)

Protein

Protein identifiers

5’-AMP-activated protein kinase subunit beta-1 — Q9Y478 (reviewed: Q9Y478)

All UniProt accessions (4): Q9Y478, F5H2X8, F5H4Y8, F5H610

UniProt curated annotations — full annotation on UniProt →

Function. Non-catalytic 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. Beta non-catalytic subunit acts as a scaffold on which the AMPK complex assembles, via its C-terminus that bridges alpha (PRKAA1 or PRKAA2) and gamma subunits (PRKAG1, PRKAG2 or PRKAG3).

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 when associated with the catalytic subunit (PRKAA1 or PRKAA2). Phosphorylated by ULK1; leading to negatively regulate AMPK activity and suggesting the existence of a regulatory feedback loop between ULK1 and AMPK.

Domain organisation. The glycogen-binding domain may target AMPK to glycogen so that other factors like glycogen-bound debranching enzyme or protein phosphatases can directly affect AMPK activity.

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

RefSeq proteins (1): NP_006244* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006828	ASC_dom	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR014756	Ig_E-set	Homologous_superfamily
IPR032640	AMPK1_CBM	Domain
IPR037256	ASC_dom_sf	Homologous_superfamily
IPR050827	CRP1_MDG1_kinase	Family

Pfam: PF04739, PF16561

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 (44 total): strand 14, modified residue 12, sequence conflict 5, helix 5, region of interest 2, initiator methionine 1, chain 1, lipid moiety-binding region 1, mutagenesis site 1, turn 1, compositionally biased region 1

Structure

Experimental structures (PDB)

12 structures.

PDB	Method	Resolution (Å)
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
4CFF	X-RAY DIFFRACTION	3.92

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y478-F1	78.16	0.58

Functional residue map

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

Post-translational modifications (13): 25, 40, 96, 101, 108, 148, 182, 2, 4, 5, 6, 19, 24

Mutagenesis-validated functional residues (1):

Position	Phenotype
2	abolishes myristoylation and amp-enhanced phosphorylation of prkaa1 or prkaa2.

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: 257 (showing top): MULLIGHAN_NPM1_SIGNATURE_3_UP, KEGG_ADIPOCYTOKINE_SIGNALING_PATHWAY, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, NKX25_02, CHIANG_LIVER_CANCER_SUBCLASS_UNANNOTATED_DN, KYNG_DNA_DAMAGE_DN, TGACCTY_ERR1_Q2, REACTOME_MEMBRANE_TRAFFICKING, LHX3_01, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, CHX10_01, GOBP_ORGANIC_ACID_BIOSYNTHETIC_PROCESS, GOBP_SMALL_MOLECULE_BIOSYNTHETIC_PROCESS, GGAANCGGAANY_UNKNOWN, GOBP_APPENDAGE_DEVELOPMENT

GO Biological Process (7): fatty acid biosynthetic process (GO:0006633), signal transduction (GO:0007165), cellular response to nutrient levels (GO:0031669), nail development (GO:0035878), positive regulation of cold-induced thermogenesis (GO:0120162), lipid metabolic process (GO:0006629), fatty acid metabolic process (GO:0006631)

GO Molecular Function (2): protein kinase binding (GO:0019901), protein binding (GO:0005515)

GO Cellular Component (6): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), 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	3
cellular response to stimulus	2
fatty acid metabolic process	1
lipid biosynthetic process	1
monocarboxylic acid biosynthetic process	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
response to nutrient levels	1
anatomical structure development	1
limb development	1
positive regulation of multicellular organismal process	1
cold-induced thermogenesis	1
regulation of cold-induced thermogenesis	1
primary metabolic process	1
lipid metabolic process	1
monocarboxylic acid metabolic process	1
kinase binding	1
binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
cytoplasm	1
intracellular protein-containing complex	1
protein kinase complex	1
cellular_component	1

Protein interactions and networks

STRING

1678 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PRKAB1	PRKAG1	P54619	998
PRKAB1	PRKAA1	Q13131	980
PRKAB1	PRKAA2	P54646	968
PRKAB1	PRKAG3	Q9UGI9	925
PRKAB1	PRKAG2	Q9UGJ0	894
PRKAB1	PRKAB2	O43741	831
PRKAB1	FLCN	Q8NFG4	700
PRKAB1	FNIP2	Q9P278	669
PRKAB1	FNIP1	Q8TF40	668
PRKAB1	MTOR	P42345	659
PRKAB1	STK11	Q15831	658
PRKAB1	CAMKK2	Q96RR4	607
PRKAB1	GEMIN6	Q8WXD5	588
PRKAB1	RPS6KB1	P23443	574
PRKAB1	TSC2	P49815	557

IntAct

268 interactions, top by confidence:

A	B	Type	Score
PRKAA1	PRKAB2	psi-mi:“MI:0914”(association)	0.950
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
PRKAB1	PRKAG1	psi-mi:“MI:0914”(association)	0.920
PRKAG1	PRKAB1	psi-mi:“MI:0915”(physical association)	0.920
PRKAA2	PRKAB1	psi-mi:“MI:0915”(physical association)	0.840
PRKAG3	PRKAB2	psi-mi:“MI:0914”(association)	0.800
PRKAB1	PRKAB2	psi-mi:“MI:0914”(association)	0.740
ULK1	PRKAG1	psi-mi:“MI:0914”(association)	0.670
ULK1	PRKAG1	psi-mi:“MI:0915”(physical association)	0.670
PRKAB1	ULK1	psi-mi:“MI:0915”(physical association)	0.640
PHKG2	PRKAB2	psi-mi:“MI:0914”(association)	0.640
MCL1	PRKAB2	psi-mi:“MI:0914”(association)	0.640
STIM2	PRKAB2	psi-mi:“MI:0914”(association)	0.640
CCKBR	PRKAG1	psi-mi:“MI:0914”(association)	0.640
PRKAB1	GRB2	psi-mi:“MI:0915”(physical association)	0.510
MAST3	PPP6C	psi-mi:“MI:0914”(association)	0.350
Prkaa1		psi-mi:“MI:0914”(association)	0.350
	PLK4	psi-mi:“MI:0914”(association)	0.350
	TBKBP1	psi-mi:“MI:0914”(association)	0.350
Ulk1	PRKAG1	psi-mi:“MI:0914”(association)	0.350
DCLRE1C	ZSWIM8	psi-mi:“MI:0914”(association)	0.350
TRIM11	BTN3A3	psi-mi:“MI:0914”(association)	0.350
PRKAG2	GEMIN2	psi-mi:“MI:0914”(association)	0.350
CUTA	UBB	psi-mi:“MI:0914”(association)	0.350
FNIP2	PRKAG1	psi-mi:“MI:0914”(association)	0.350
PRKAA2	PPP6C	psi-mi:“MI:0914”(association)	0.350

BioGRID (214): CIDEA (Affinity Capture-Western), PRKAG1 (Affinity Capture-Western), PRKAA1 (Affinity Capture-Western), PRKAB1 (Affinity Capture-Western), ACACA (Biochemical Activity), PRKAB1 (Two-hybrid), PRKAG1 (Two-hybrid), PRKAA1 (Two-hybrid), PRKAB1 (Two-hybrid), SNF1 (Two-hybrid), SNF4 (Two-hybrid), PRKAA1 (Reconstituted Complex), PRKAG1 (Reconstituted Complex), PRKAB1 (Reconstituted Complex), PRKAB1 (Reconstituted Complex)

ESM2 similar proteins: A6H6W9, D3Z7P3, G3MWR8, O14639, O43741, O94925, P13264, P42232, P51692, P60762, Q12800, Q13042, Q1RLU8, Q3MHJ2, Q4V860, Q4W5Z4, Q5BIS9, Q5F450, Q5NVP9, Q5R801, Q5RBB8, Q5RBN9, Q5RCB7, Q5ZJB7, Q5ZJV7, Q6AYJ2, Q6AYU1, Q6NRB5, Q6NZH6, Q6PAM0, Q6UXG2, Q7RTP6, Q7T2U9, Q7Z6J6, Q86TJ2, Q8BR65, Q8C8M1, Q8CJ19, Q8K4Q0, Q8R349

Diamond homologs: F4KFB3, O43741, P34164, P78789, P80386, P80387, Q10F03, Q5BIS9, Q5R801, Q6PAM0, Q84VQ1, Q944A6, Q9FEB5, Q9LFY0, Q9QZH4, Q9R078, Q9SCY5, Q9Y478, Q9ZUU8, A6ZT54, B3LSR0, C7GJZ2, C8Z9U3, E7KDM2, E7KPJ0, E7LVH4, E7NIP0, E7Q4T7, P38845, Q04739, Q94AX2, G4LTX4, F4J117, O54950, P54619, Q09138, Q5R4S0, Q8T277, Q91WG5, Q9UGJ0

SIGNOR signaling

8 interactions.

A	Effect	B	Mechanism
PRKAB1	up-regulates	NOS3	phosphorylation
PRKAB1	“form complex”	AMPK	binding
PRKAA1	up-regulates	PRKAB1	phosphorylation
PRKAB1	down-regulates	RPTOR	phosphorylation
PRKAB1	up-regulates	ULK1	phosphorylation
ULK2	down-regulates	PRKAB1	phosphorylation
PRKAB1	“down-regulates quantity by destabilization”	PROX1	phosphorylation
PRKAB1	“down-regulates activity”	STIM1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 172 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
AMPK-induced ERAD and lysosome mediated degradation of PD-L1(CD274)	15	20.0×	3e-13
AUF1 (hnRNP D0) binds and destabilizes mRNA	11	18.8×	2e-09
Regulation of activated PAK-2p34 by proteasome mediated degradation	9	17.3×	2e-07
Vpu mediated degradation of CD4	9	16.5×	2e-07
Autodegradation of the E3 ubiquitin ligase COP1	9	16.5×	2e-07
Ubiquitin-dependent degradation of Cyclin D	9	16.5×	2e-07
Energy dependent regulation of mTOR by LKB1-AMPK	6	16.3×	2e-05
Vif-mediated degradation of APOBEC3G	9	15.8×	2e-07

GO biological processes:

GO term	Partners	Fold	FDR
cellular response to nutrient levels	8	22.3×	2e-06
translational initiation	7	14.9×	2e-04
fatty acid biosynthetic process	7	14.6×	2e-04
regulation of translational initiation	5	13.9×	3e-03
protein folding	9	5.5×	4e-03
proteasome-mediated ubiquitin-dependent protein catabolic process	13	4.0×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	28
Likely benign	0
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1634 predictions. Top by Δscore:

Variant	Effect	Δscore
12:119667953:G:GT	donor_gain	1.0000
12:119667959:G:GT	donor_gain	1.0000
12:119667990:A:T	donor_gain	1.0000
12:119672409:G:GT	donor_gain	1.0000
12:119672461:GAAG:G	donor_gain	1.0000
12:119672464:GGTAA:G	donor_loss	1.0000
12:119672465:GT:G	donor_loss	1.0000
12:119672466:T:G	donor_loss	1.0000
12:119676533:ACAGA:A	acceptor_loss	1.0000
12:119676535:A:AG	acceptor_gain	1.0000
12:119676536:G:C	acceptor_loss	1.0000
12:119676536:G:GG	acceptor_gain	1.0000
12:119676536:GA:G	acceptor_gain	1.0000
12:119676536:GAGCT:G	acceptor_gain	1.0000
12:119676671:G:GG	donor_gain	1.0000
12:119679928:CACA:C	acceptor_loss	1.0000
12:119679930:CAG:C	acceptor_loss	1.0000
12:119679931:A:AG	acceptor_gain	1.0000
12:119679931:A:T	acceptor_loss	1.0000
12:119679931:AGT:A	acceptor_gain	1.0000
12:119679931:AGTGT:A	acceptor_gain	1.0000
12:119679932:G:GG	acceptor_gain	1.0000
12:119679932:GT:G	acceptor_gain	1.0000
12:119679932:GTG:G	acceptor_gain	1.0000
12:119679932:GTGT:G	acceptor_gain	1.0000
12:119679932:GTGTG:G	acceptor_gain	1.0000
12:119680243:CTTAG:C	acceptor_loss	1.0000
12:119680245:TAG:T	acceptor_loss	1.0000
12:119680246:A:AG	acceptor_gain	1.0000
12:119680246:AG:A	acceptor_gain	1.0000

AlphaMissense

1787 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:119672424:G:T	G95W	1.000
12:119672425:G:A	G95E	1.000
12:119673993:T:C	L118P	1.000
12:119674013:T:G	Y125D	1.000
12:119674375:C:A	N151K	1.000
12:119674375:C:G	N151K	1.000
12:119676621:T:A	L206H	1.000
12:119676633:T:C	L210P	1.000
12:119676648:T:A	L215Q	1.000
12:119676648:T:C	L215P	1.000
12:119676652:C:A	N216K	1.000
12:119676652:C:G	N216K	1.000
12:119679949:T:A	L228H	1.000
12:119679949:T:C	L228P	1.000
12:119679957:C:T	P231S	1.000
12:119679958:C:A	P231H	1.000
12:119679958:C:G	P231R	1.000
12:119679967:T:A	V234D	1.000
12:119679973:T:C	L236P	1.000
12:119679978:C:A	H238N	1.000
12:119679978:C:G	H238D	1.000
12:119679978:C:T	H238Y	1.000
12:119679979:A:C	H238P	1.000
12:119679979:A:G	H238R	1.000
12:119679979:A:T	H238L	1.000
12:119679980:C:A	H238Q	1.000
12:119679980:C:G	H238Q	1.000
12:119679982:T:C	L239P	1.000
12:119679984:T:G	Y240D	1.000
12:119679988:C:A	A241E	1.000

dbSNP variants (sampled 300 via entrez): RS1000823190 (12:119681204 T>TA), RS1000985107 (12:119666051 C>G,T), RS1001160938 (12:119670025 C>G), RS1001874302 (12:119671130 C>T), RS1001881694 (12:119673237 A>G), RS1001911033 (12:119672990 G>T), RS1001986004 (12:119677957 G>C), RS1002085783 (12:119666929 G>A), RS1002149021 (12:119671682 G>A), RS1002505953 (12:119681960 G>T), RS1002552229 (12:119676125 C>T), RS1002584881 (12:119675842 A>T), RS1002663261 (12:119666492 T>C), RS1002758065 (12:119669831 G>A,T), RS1002968585 (12:119681807 C>G)

Disease associations

OMIM: gene MIM:602740 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST003043_92	Inflammatory bowel disease	6.000000e-08
GCST003045_69	Ulcerative colitis	2.000000e-07
GCST011878_18	Mitochondrial heteroplasmy measurement	1.000000e-08
GCST90002379_56	Basophil count	5.000000e-15
GCST90002389_468	Lymphocyte percentage of white cells	2.000000e-11
GCST90002393_599	Monocyte count	9.000000e-10
GCST90002398_151	Neutrophil count	2.000000e-18
GCST90002400_733	Plateletcrit	7.000000e-11
GCST90002407_296	White blood cell count	2.000000e-16

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0600008	mitochondrial heteroplasmy measurement
EFO:0005090	basophil count
EFO:0007993	lymphocyte percentage of leukocytes
EFO:0005091	monocyte count
EFO:0004833	neutrophil count
EFO:0007985	platelet crit

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (8): CHEMBL2096907 (PROTEIN COMPLEX GROUP), CHEMBL2111345 (PROTEIN COMPLEX), CHEMBL3038451 (PROTEIN COMPLEX), CHEMBL3038452 (PROTEIN COMPLEX), CHEMBL3038455 (PROTEIN COMPLEX), CHEMBL3847 (SINGLE PROTEIN), CHEMBL3885504 (PROTEIN COMPLEX), CHEMBL4106159 (PROTEIN COMPLEX)

Molecules with ChEMBL bioactivity

5 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 168,512 (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
CHEMBL473659	GINSENOSIDE RD	3	1,735
CHEMBL3544911	PREXASERTIB	2	699
CHEMBL3128043	PF-03758309	1	233
CHEMBL4169078	SRA-737	1	529

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — AMPK subfamily

Most potent curated ligand interactions (1 total), top 1:

Ligand	Action	Affinity	Parameter
MT47-100	Activation	5.43	pKi

Binding affinities (BindingDB)

319 measured of 323 human assays (323 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

684 potent at pChembl≥5 of 741 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
9.15	EC50	0.7	nM	CHEMBL3979403
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

PubChem BioAssay actives

355 with measured affinity, of 2023 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
[6-chloro-2-hydroxy-5-(1-methylindol-5-yl)-1H-indol-3-yl]-(3-methoxy-1,2-oxazol-5-yl)methanone	1320676: Activation of recombinant human His-tagged AMPK alpha2 (2 to 552 residues)/beta1 (2 to 270 residues)/gamma2 (2 to 569 residues) expressed in baculovirus infected sf21 cells preincubated for 30 mins followed by biotinylated ACC-CREBp peptide substrate addition measured after 45 mins by HTRF assay	ec50	0.0007	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
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
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	1320694: Activation of human recombinant AMPK alpha1/beta1/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	0.0110	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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases expression	3
Cisplatin	increases expression	3
Aflatoxin B1	increases expression	3
bisphenol A	affects cotreatment, decreases methylation, decreases expression	2
Rotenone	decreases expression, increases expression	2
Cyclosporine	decreases expression, increases expression	2
aristolochic acid I	increases expression	1
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
FR900359	increases phosphorylation	1
2,4,6-tribromophenol	decreases expression	1
chloroacetaldehyde	affects expression	1
alpha-pinene	increases oxidation, increases abundance, affects cotreatment	1
morin	decreases expression	1
testosterone undecanoate	affects cotreatment, increases expression	1
decabromobiphenyl ether	decreases expression	1
sodium arsenite	increases expression	1
dioscin	increases expression	1
tetrabromobisphenol A	decreases expression	1
methacrylaldehyde	increases abundance, affects cotreatment, increases oxidation	1
di-n-butylphosphoric acid	affects expression	1
nutlin 3	affects cotreatment, increases expression	1
abrine	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Acrolein	affects cotreatment, increases oxidation, increases abundance	1
Adenine	decreases expression	1
Air Pollutants	affects cotreatment, increases abundance, increases oxidation	1
Ammonium Chloride	affects phosphorylation, affects reaction, affects response to substance, affects expression	1

ChEMBL screening assays

484 unique, capped per target: 483 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

11 cell lines: 10 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D1Q2	Abcam K-562 PRKAB1 KO	Cancer cell line	Female
CVCL_D2LN	Abcam Raji PRKAB1 KO	Cancer cell line	Male
CVCL_D7YB	Ubigene A-549 PRKAB1 KO	Cancer cell line	Male
CVCL_D8TS	Ubigene HCT 116 PRKAB1 KO	Cancer cell line	Male
CVCL_D9PE	Ubigene HEK293 PRKAB1 KO	Transformed cell line	Female
CVCL_E0LQ	Ubigene HeLa PRKAB1 KO	Cancer cell line	Female
CVCL_TG64	HAP1 PRKAB1 (-) 1	Cancer cell line	Male
CVCL_TG65	HAP1 PRKAB1 (-) 2	Cancer cell line	Male
CVCL_TG66	HAP1 PRKAB1 (-) 3	Cancer cell line	Male
CVCL_TG67	HAP1 PRKAB1 (-) 4	Cancer cell line	Male

Clinical trials (associated diseases)

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