PFKFB3

Summary

PFKFB3 (6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3, HGNC:8874) is a protein-coding gene on chromosome 10p15.1, encoding 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (Q16875). Catalyzes both the synthesis and degradation of fructose 2,6-bisphosphate.

The protein encoded by this gene belongs to a family of bifunctional proteins that are involved in both the synthesis and degradation of fructose-2,6-bisphosphate, a regulatory molecule that controls glycolysis in eukaryotes. The encoded protein has a 6-phosphofructo-2-kinase activity that catalyzes the synthesis of fructose-2,6-bisphosphate (F2,6BP), and a fructose-2,6-biphosphatase activity that catalyzes the degradation of F2,6BP. This protein is required for cell cycle progression and prevention of apoptosis. It functions as a regulator of cyclin-dependent kinase 1, linking glucose metabolism to cell proliferation and survival in tumor cells. Several alternatively spliced transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 5209 — RefSeq curated summary.

At a glance

• GWAS associations: 14
• Clinical variants (ClinVar): 94 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_004566

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8874
Approved symbol	PFKFB3
Name	6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3
Location	10p15.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000170525
Ensembl biotype	protein_coding
OMIM	605319
Entrez	5209

Gene structure

Transcript identifiers

Ensembl transcripts: 24 — 18 protein_coding, 5 nonsense_mediated_decay, 1 retained_intron

ENST00000317350, ENST00000360521, ENST00000379775, ENST00000379785, ENST00000379789, ENST00000414237, ENST00000441697, ENST00000450232, ENST00000461744, ENST00000467491, ENST00000475881, ENST00000477914, ENST00000487989, ENST00000490474, ENST00000536985, ENST00000625260, ENST00000626882, ENST00000639949, ENST00000640683, ENST00000900115, ENST00000900116, ENST00000937281, ENST00000937282, ENST00000937283

RefSeq mRNA: 7 — MANE Select: NM_004566 NM_001145443, NM_001282630, NM_001314063, NM_001323016, NM_001323017, NM_001363545, NM_004566

CCDS: CCDS44353, CCDS60479, CCDS7078, CCDS81439, CCDS86068

Canonical transcript exons

ENST00000379775 — 15 exons

Exon	Start	End
ENSE00001625550	6216125	6216191
ENSE00001626155	6222855	6222984
ENSE00001636131	6213623	6213748
ENSE00001643662	6232895	6235532
ENSE00001650689	6217135	6217191
ENSE00001672633	6219569	6219693
ENSE00001691710	6215221	6215317
ENSE00001748558	6216706	6216780
ENSE00001758318	6221641	6221745
ENSE00003497587	6224149	6224213
ENSE00003518628	6223958	6224020
ENSE00003644790	6226192	6226365
ENSE00003712496	6221381	6221527
ENSE00003748307	6220658	6220865
ENSE00003802369	6202932	6203336

Expression profiles

Bgee: expression breadth ubiquitous, 288 present calls, max score 99.27.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 78.3777 / max 2326.6990, expressed in 1819 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
103681	54.4226	1753
103676	18.9707	1794
103677	3.6243	1419
103682	0.9777	316
103689	0.3825	183

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
pancreatic ductal cell	CL:0002079	99.27	gold quality
renal medulla	UBERON:0000362	99.08	gold quality
endothelial cell	CL:0000115	98.87	gold quality
subcutaneous adipose tissue	UBERON:0002190	98.36	gold quality
medial globus pallidus	UBERON:0002477	98.26	gold quality
adipose tissue	UBERON:0001013	98.25	gold quality
gastrocnemius	UBERON:0001388	98.25	gold quality
lower lobe of lung	UBERON:0008949	98.12	gold quality
periodontal ligament	UBERON:0008266	98.09	gold quality
globus pallidus	UBERON:0001875	98.07	gold quality
connective tissue	UBERON:0002384	97.86	gold quality
cervix squamous epithelium	UBERON:0006922	97.80	gold quality
lateral globus pallidus	UBERON:0002476	97.58	gold quality
metanephros cortex	UBERON:0010533	97.58	gold quality
mucosa of stomach	UBERON:0001199	97.51	gold quality
adipose tissue of abdominal region	UBERON:0007808	97.51	gold quality
muscle of leg	UBERON:0001383	97.43	gold quality
omental fat pad	UBERON:0010414	97.40	gold quality
peritoneum	UBERON:0002358	97.37	gold quality
Brodmann (1909) area 23	UBERON:0013554	97.37	gold quality
epithelial cell of pancreas	CL:0000083	97.32	gold quality
gluteal muscle	UBERON:0002000	97.29	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	97.27	gold quality
superior vestibular nucleus	UBERON:0007227	97.21	gold quality
hindlimb stylopod muscle	UBERON:0004252	97.09	gold quality
tibialis anterior	UBERON:0001385	97.04	gold quality
medulla oblongata	UBERON:0001896	97.01	gold quality
descending thoracic aorta	UBERON:0002345	96.96	gold quality
epithelium of mammary gland	UBERON:0003244	96.89	gold quality
ascending aorta	UBERON:0001496	96.87	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-GEOD-36552	yes	193.07
E-CURD-119	yes	22.86
E-ANND-3	yes	20.08
E-CURD-46	yes	11.12
E-MTAB-6678	yes	5.63
E-GEOD-75367	no	109.88

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): APP, CEBPG, HIF1A, IFNG, MLXIP, NR1H3, PGR, PSEN1, SRF, VEZF1

miRNA regulators (miRDB)

108 targeting PFKFB3, 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-5692A	100.00	74.40	6850
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-589-3P	99.91	69.62	2088
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-7-1-3P	99.91	71.53	4384

Literature-anchored findings (GeneRIF, showing 40)

• The results show the expression of the pfkfb3 gene in and its downregulation during myogenic cell differentiation, the decrease of uPFK-2 isozyme levels, product of pfkfb3 gene, is due to its degradation through the ubiquitin-proteasome pathway (PMID:12935880)
• PFKFB3 cloning and characterization (PMID:12963966)
• pfkfb3 is a hypoxia-inducible gene that is stimulated through HIF interaction with the consensus HRE site in its promoter region (PMID:15466858)
• kinase activity of human brain 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase is regulated via inhibition by phosphoenolpyruvate (PMID:15896703)
• Findings support a potential role for the phosphorylation of PFKFB3 protein in the progression of cancer and angiogenesis. (PMID:16115917)
• Insulin induces the phosphorylation of PFKFB3 protein, expanding the role of these structurally unique iPFK-2/PFKFB3 isoforms in the metabolic regulation of adipocytes. (PMID:16306349)
• Our results clearly demonstrated the existence of splice isoform of PFKFB-4 mRNA in the DB-1 melanoma cells and its overexpression under hypoxic conditions. (PMID:16311927)
• The results obtained highlight the importance of uPFK-2 on the regulation of glycolysis, on cell viability and proliferation and also on anchorage-independent growth. (PMID:16698023)
• PFKFB-4 and PFKFB-3 genes are expressed in gastric and pancreatic cancer cells, they strongly respond to hypoxia via a HIF-1alpha dependent mechanism and possibly have a significant role in the Warburg effect which is found in malignant cells (PMID:17143338)
• Results show a direct substrate-substrate interaction in the kinase domain of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFKFB3). (PMID:17499765)
• PFK-2/FBPase-2 protein rather than its product fructose 2,6-P(2) is the over-riding determinant of glucose-induced insulin secretion through regulation of glucokinase activity or subcellular targeting. (PMID:18039179)
• ectopic expression of PFKFB3 increased the expression of several key cell cycle proteins, including cyclin-dependent kinase (Cdk)-1, Cdc25C, and cyclin D3 and decreased the expression of the cell cycle inhibitor p27 (PMID:19473963)
• Our results demonstrate that the splice variant UBI2K4 impedes the tumour cell growth and might serve as a tumour suppressor in astrocytic tumours. (PMID:19490427)
• Glycolysis-promoting enzyme 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase, isoform 3 (PFKFB3), is degraded by the E3 ubiquitin ligase APC/C-Cdh1. (PMID:20080744)
• Interleukin 6 enhances glycolysis through expression of the glycolytic enzymes hexokinase 2 and 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase-3. (PMID:20453422)
• Data demonstrate that PFKFB3 is essential for cell division and that it is regulated by APC/C-Cdh1 and SKP1-CUL1-F (SCF)-beta-TrCP. (PMID:21402913)
• inducible PFKFB3 is required for increased growth, metabolic activity and is regulated through active JAK2 and STAT5. (PMID:21860432)
• The allelic deletion of PFKFB3 resulted in a decrease of PFKFB3 mRNA level accompanied by a lower PFKFB3 protein level. (PMID:21987444)
• The breakdown of PFKFB3 during S phase occurs specifically via a distinct residue (S(273)) within the conserved recognition site for SCF-beta-TrCP. (PMID:22106309)
• Low bisphosphatase activity of PFKFB3 is solely due to the presence of a serine at residue 302. (PMID:22275052)
• Stress stimuli affect PFKFB3 transcriptional regulation and kinase activation by protein phosphorylation and glycolysis in cancer cells. (PMID:23548149)
• Study showed that endothelial cells (ECs)relied on glycolysis rather than on oxidative phosphorylation for ATP production and that loss of the glycolytic activator PFKFB3 in ECs impaired vessel formation. (PMID:23911327)
• Phosphofructokinase deficiency impairs ATP generation, autophagy, and redox balance in rheumatoid arthritis T cells. (PMID:24043759)
• Because deregulation of endometrial SRC-2 expression has been associated with common gynecological disorders of reproductive-age women, this signaling pathway, involving SRC-2 and PFKFB3 (PMID:24204309)
• PFKFB3 regulates oxidative stress homeostasis via its S-glutathionylation in cancer. (PMID:24295899)
• blockade of PFKFB3 by the small molecule 3-(3-pyridinyl)-1-(4-pyridinyl)-2-propen-1-one (3PO) reduced vessel sprouting. (PMID:24332967)
• estrogen receptor directly promotes PFKFB3 mRNA transcription (PMID:24515104)
• Reduced methylation of PFKFB3 shifted glucose utilization from glycolysis toward the pentose phosphate pathway. (PMID:24633012)
• PFKFB3 is a promising target for the reduction of endothelial glycolysis and its related pathological angiogenesis (PMID:24700124)
• PFKFB3 promotes cell cycle progression and suppresses apoptosis via Cdk1-mediated phosphorylation of p27. (PMID:25032860)
• Shear stress-mediated repression of endothelial cell metabolism via KLF2 and PFKFB3 controls endothelial cell phenotype. (PMID:25359860)
• A binding site for miR-26b was predicted in the 3’UTR of PFKFB3. miR-26b overexpression repressed PFKFB3 mRNA and protein levels. (PMID:25672572)
• study demonstrated that miR-206 regulated PFKFB3 expression in breast cancer cells, thereby stunting glycolysis, cell proliferation and migration (PMID:26093295)
• Shh regulates PFKFB3 activation in breast cancer cells. (PMID:26171876)
• Data show that inhibition of AMP-Activated kinase (AMPK) or 6-phosphofructo-2-kinase-fructose-2,6-biphosphatase 3 (PFKFB3) results in enhanced cell death in mitosis. (PMID:26322680)
• Data indicate that 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase3 (PFKFB3) and phosphofructokinase (PFK1) expression allows discrimination between induced pluripotent stem cells (iPS) and cancer stem cells (CSCs). (PMID:26337471)
• Our data suggest that chronic inflammation promotes the development of CRC by stimulating aerobic glycolysis and IL-6 is functioning, at least partly, through regulating PFKFB3 at early stage of colorectal cancer (CRC). (PMID:26530697)
• MicroRNA-26b inhibits osteosarcoma cell migration and invasion by down-regulating PFKFB3 expression (PMID:26681033)
• a novel role of PFKFB3 in glycolytic metabolism and ER stress of OA cartilage explants and chondrocytes (PMID:26718307)
• Insulin resistance in obese boys leads to up-regulation of INSIG2 gene expression as well as to down-regulation of PFKFB1, PFKFB3, and HK2 genes in the blood cells as compared to obese patients with normal insulin sensitivity. (PMID:26827442)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	pfkfb3	ENSDARG00000001953
mus_musculus	Pfkfb3	ENSMUSG00000026773
rattus_norvegicus	Pfkfb3	ENSRNOG00000018911
drosophila_melanogaster	Pfrx	FBGN0027621
caenorhabditis_elegans		WBGENE00019295
caenorhabditis_elegans	pfkb-1.1	WBGENE00022456

Paralogs (3): PFKFB4 (ENSG00000114268), PFKFB2 (ENSG00000123836), PFKFB1 (ENSG00000158571)

Protein

Protein identifiers

6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 — Q16875 (reviewed: Q16875)

Alternative names: 6PF-2-K/Fru-2,6-P2ase brain/placenta-type isozyme, Renal carcinoma antigen NY-REN-56, iPFK-2

All UniProt accessions (10): Q16875, A0A1W2PNV9, A0A1W2PR17, F2Z2I2, H0Y483, H0YDV0, Q5VX20, Q5W015, Q9BQU1, Q9H178

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes both the synthesis and degradation of fructose 2,6-bisphosphate.

Subunit / interactions. Homodimer. Forms a heterodimer with PFKFB2.

Tissue specificity. Ubiquitous.

Post-translational modifications. Phosphorylation by AMPK stimulates activity.

Similarity. In the C-terminal section; belongs to the phosphoglycerate mutase family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q16875-1	1	yes
Q16875-2	2
Q16875-3	3
Q16875-4	4

RefSeq proteins (7): NP_001138915, NP_001269559, NP_001300992, NP_001309945, NP_001309946, NP_001350474, NP_004557* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001345	PG/BPGM_mutase_AS	Active_site
IPR003094	6Pfruct_kin	Family
IPR013078	His_Pase_superF_clade-1	Family
IPR013079	6Phosfructo_kin	Domain
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR029033	His_PPase_superfam	Homologous_superfamily

Pfam: PF00300, PF01591

Enzyme classification (BRENDA):

• EC 2.7.1.105 — 6-phosphofructo-2-kinase (BRENDA: 25 organisms, 68 substrates, 145 inhibitors, 158 Km, 41 kcat entries)
• EC 3.1.3.46 — fructose-2,6-bisphosphate 2-phosphatase (BRENDA: 28 organisms, 27 substrates, 93 inhibitors, 21 Km, 1 kcat entries)

Substrate kinetics (BRENDA)

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

Substrate	Km (mM)	Measurements
BETA-D-FRUCTOSE 6-PHOSPHATE	0.0038–39	63
ATP	0.0009–1.62	35
MGATP2-	0.0072–2	21
FRUCTOSE 2,6-BISPHOSPHATE	0.0001–1.4	15
D-FRUCTOSE 6-PHOSPHATE	0.0094–0.1	4
BETA-D-FRUCTOSE 2,6-BISPHOSPHATE	0.0102–0.204	3
BETA-D-FRUCTOSE 2,6-BISPHOSPHATE	0.02–0.21	2
CTP	0.9–2	2
GTP	0.35–1.5	2
UTP	0.78–2.3	2
D-PSICOSE 6-PHOSPHATE	7.4	1
D-TAGATOSE 6-PHOSPHATE	15	1
ITP	0.3	1
L-SORBOSE 6-PHOSPHATE	0.175	1
D-FRUCTOSE 2,6-BISPHOSPHATE	0.0001	1

Catalyzed reactions (Rhea), 2 shown:

• beta-D-fructose 6-phosphate + ATP = beta-D-fructose 2,6-bisphosphate + ADP + H(+) (RHEA:15653)
• beta-D-fructose 2,6-bisphosphate + H2O = beta-D-fructose 6-phosphate + phosphate (RHEA:17289)

UniProt features (89 total): binding site 21, helix 21, strand 17, turn 7, modified residue 4, active site 4, region of interest 3, site 3, splice variant 3, mutagenesis site 2, sequence conflict 2, chain 1, compositionally biased region 1

Structure

Experimental structures (PDB)

26 structures.

PDB	Method	Resolution (Å)
6HVI	X-RAY DIFFRACTION	1.96
5AK0	X-RAY DIFFRACTION	2.03
2AXN	X-RAY DIFFRACTION	2.1
6IBX	X-RAY DIFFRACTION	2.11
4MA4	X-RAY DIFFRACTION	2.23
2DWO	X-RAY DIFFRACTION	2.25
3QPW	X-RAY DIFFRACTION	2.25
6HVJ	X-RAY DIFFRACTION	2.28
3QPU	X-RAY DIFFRACTION	2.3
4D4M	X-RAY DIFFRACTION	2.32
5AJZ	X-RAY DIFFRACTION	2.35
6HVH	X-RAY DIFFRACTION	2.36
5AJY	X-RAY DIFFRACTION	2.37
6IBZ	X-RAY DIFFRACTION	2.44
2I1V	X-RAY DIFFRACTION	2.5
3QPV	X-RAY DIFFRACTION	2.5
5AJW	X-RAY DIFFRACTION	2.5
6ETJ	X-RAY DIFFRACTION	2.51
6IBY	X-RAY DIFFRACTION	2.51
5AJX	X-RAY DIFFRACTION	2.58
6IC0	X-RAY DIFFRACTION	2.6
2DWP	X-RAY DIFFRACTION	2.7
4D4J	X-RAY DIFFRACTION	3
5AJV	X-RAY DIFFRACTION	3.01
4D4L	X-RAY DIFFRACTION	3.16
4D4K	X-RAY DIFFRACTION	3.24

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q16875-F1	87.31	0.77

Functional residue map

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

Catalytic / active sites (7): 253 (transition state stabilizer); 260 (transition state stabilizer); 388 (transition state stabilizer); 125; 155; 254 (tele-phosphohistidine intermediate); 323 (proton donor/acceptor)

Ligand- & substrate-binding residues (21): 75; 99; 127; 133; 164–169; 169; 190; 194; 253; 260; 266; 334 …

Post-translational modifications (4): 461, 463, 467, 471

Mutagenesis-validated functional residues (2):

Position	Phenotype
45	20-fold decrease in km for atp and 3-fold decrease in km for fructose-6 phsphate.
169	loss of activity.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-9634600	Regulation of glycolysis by fructose 2,6-bisphosphate metabolism

MSigDB gene sets: 391 (showing top): GGGACCA_MIR133A_MIR133B, RNGTGGGC_UNKNOWN, GOBP_NUCLEOSIDE_DIPHOSPHATE_METABOLIC_PROCESS, SHEPARD_CRASH_AND_BURN_MUTANT_UP, SP3_Q3, MODULE_45, MODULE_64, MENSE_HYPOXIA_UP, GOBP_CARBOHYDRATE_DERIVATIVE_CATABOLIC_PROCESS, GOBP_CARBOHYDRATE_PHOSPHORYLATION, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, FOXO4_01, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, NAGASHIMA_NRG1_SIGNALING_UP, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS

GO Biological Process (8): fructose metabolic process (GO:0006000), fructose 2,6-bisphosphate metabolic process (GO:0006003), gluconeogenesis (GO:0006094), glycolytic process (GO:0006096), apoptotic process (GO:0006915), glial cell differentiation (GO:0010001), motor behavior (GO:0061744), carbohydrate phosphorylation (GO:0046835)

GO Molecular Function (9): 6-phosphofructo-2-kinase activity (GO:0003873), fructose-2,6-bisphosphate 2-phosphatase activity (GO:0004331), ATP binding (GO:0005524), nucleotide binding (GO:0000166), catalytic activity (GO:0003824), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740), hydrolase activity (GO:0016787)

GO Cellular Component (3): nucleoplasm (GO:0005654), cytosol (GO:0005829), 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase complex (GO:0043540)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Glycolysis	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
catalytic activity	2
cellular anatomical structure	2
hexose metabolic process	1
organophosphate metabolic process	1
carbohydrate derivative metabolic process	1
glucose metabolic process	1
hexose biosynthetic process	1
phosphoglycerate kinase activity	1
phosphoglycerate mutase activity	1
phosphopyruvate hydratase activity	1
pyruvate kinase activity	1
pyruvate metabolic process	1
generation of precursor metabolites and energy	1
aerobic respiration	1
carbohydrate catabolic process	1
pyridine nucleotide catabolic process	1
glyceraldehyde-3-phosphate dehydrogenase [NAD(P)+] (phosphorylating) activity	1
ADP catabolic process	1
ATP metabolic process	1
nicotinamide nucleotide metabolic process	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
cell differentiation	1
gliogenesis	1
behavior	1
carbohydrate metabolic process	1
phosphorylation	1
phosphofructokinase activity	1
sugar-phosphatase activity	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
molecular_function	1
binding	1
transferase activity, transferring phosphorus-containing groups	1
nuclear lumen	1
cytoplasm	1
cytosol	1

Protein interactions and networks

STRING

2200 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PFKFB3	PFKM	P08237	956
PFKFB3	GCK	P35557	858
PFKFB3	LDHA	P00338	837
PFKFB3	PKM	P14618	753
PFKFB3	HK2	P52789	722
PFKFB3	SLC2A1	P11166	722
PFKFB3	FBP2	O00757	694
PFKFB3	HIF1A	Q16665	666
PFKFB3	H6PD	O95479	665
PFKFB3	PFKL	P17858	634
PFKFB3	PFKP	Q01813	630
PFKFB3	PGK1	P00558	626
PFKFB3	TIGAR	Q9NQ88	625
PFKFB3	IL1B	P01584	623
PFKFB3	SLC2A3	P11169	611

IntAct

52 interactions, top by confidence:

A	B	Type	Score
SH3KBP1	USP27X	psi-mi:“MI:0914”(association)	0.640
YWHAH	PLEKHG3	psi-mi:“MI:0914”(association)	0.610
DCAF7	PFDN6	psi-mi:“MI:0914”(association)	0.570
PFKFB1	PFKFB3	psi-mi:“MI:0915”(physical association)	0.560
YWHAQ	IGLC7	psi-mi:“MI:0914”(association)	0.530
LRRTM1	UPK3BL1	psi-mi:“MI:0914”(association)	0.530
PES1	AP3B1	psi-mi:“MI:0914”(association)	0.530
YWHAB	PLEKHG3	psi-mi:“MI:0914”(association)	0.480
PFKFB3	PFKFB3	psi-mi:“MI:0407”(direct interaction)	0.440
PFKFB3		psi-mi:“MI:0915”(physical association)	0.400
ARRB1		psi-mi:“MI:0914”(association)	0.350
ARRB2		psi-mi:“MI:0914”(association)	0.350
NEK4	E2F8	psi-mi:“MI:0914”(association)	0.350
NEK4	QSOX1	psi-mi:“MI:0914”(association)	0.350
PFKFB3	DNAJC7	psi-mi:“MI:0914”(association)	0.350
YWHAB	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
YWHAG	C1orf226	psi-mi:“MI:0914”(association)	0.350
YWHAZ	SPEG	psi-mi:“MI:0914”(association)	0.350
RALBP1	HMGB1P1	psi-mi:“MI:0914”(association)	0.350
PEBP1	PRPSAP2	psi-mi:“MI:0914”(association)	0.350
EGFR	ACTB	psi-mi:“MI:0914”(association)	0.350
PTPRR	MRPS14	psi-mi:“MI:0914”(association)	0.350
FGFR1	MRPS14	psi-mi:“MI:0914”(association)	0.350
rep	ATP5F1B	psi-mi:“MI:0914”(association)	0.350
rep	NKRF	psi-mi:“MI:0914”(association)	0.350
M		psi-mi:“MI:0914”(association)	0.350
CTBP1	TAF15	psi-mi:“MI:0914”(association)	0.350

BioGRID (83): PFKFB3 (Affinity Capture-MS), PFKFB4 (Affinity Capture-MS), PFKFB2 (Affinity Capture-MS), PFKFB3 (Affinity Capture-MS), CLUH (Affinity Capture-MS), PFKFB3 (Affinity Capture-MS), PFKFB3 (Affinity Capture-RNA), PFKFB3 (Affinity Capture-MS), PFKFB3 (Co-localization), PFKFB3 (Co-localization), PFKFB3 (Co-localization), PFKFB3 (Affinity Capture-MS), PFKFB3 (PCA), PFKFB3 (Affinity Capture-MS), PFKFB3 (Affinity Capture-MS)

ESM2 similar proteins: A0A4X1T4U3, A4IFD0, O00329, O14936, O35904, O61069, O65583, O70589, P07953, P16118, P25114, P49872, P70266, Q13057, Q16875, Q16877, Q24210, Q28901, Q298L5, Q2UM43, Q32M07, Q4R3W4, Q4R8B6, Q4V8A1, Q502L7, Q5B5L3, Q5M7G4, Q5R9C1, Q623S8, Q62915, Q68FP8, Q6DGQ8, Q6DTY7, Q6P618, Q80UN9, Q8IMX7, Q8MIR4, Q91309, Q91348, Q91YL3

Diamond homologs: A1AJW4, A1JJB8, A1TC01, A1WDX2, A2SDN6, A4T096, A4TQH5, A4W6B3, A6TI09, A6WYJ2, A7FMF8, A7MIJ0, A7ZVT7, A8A8C4, A8ALW1, A8G9J4, A9MR94, A9N7F5, A9R032, B0SY17, B1IS24, B1JL20, B1LEK2, B1XFK5, B2K3K5, B2TZS8, B2VH13, B4EY52, B4T4I9, B4TH18, B4TU55, B5BAL1, B5F543, B5FTD9, B5R3B7, B5R9W3, B5Y264, B5Z4S7, B6I6P3, B7LEP1

SIGNOR signaling

12 interactions.

A	Effect	B	Mechanism
AKT	up-regulates	PFKFB3	phosphorylation
AMPK	up-regulates	PFKFB3	phosphorylation
AKT1	up-regulates	PFKFB3	phosphorylation
PFKFB3	“up-regulates quantity”	“beta-D-fructofuranose 2,6-bisphosphate”	“chemical modification”
APC-c	“down-regulates quantity by destabilization”	PFKFB3	ubiquitination
FZR1	“down-regulates quantity by destabilization”	PFKFB3	binding
PIM2	“up-regulates quantity by stabilization”	PFKFB3	phosphorylation
MAPK12	“up-regulates quantity”	PFKFB3	phosphorylation
PRKAA1	up-regulates	PFKFB3	phosphorylation
“HIF-1 complex”	“up-regulates quantity by expression”	PFKFB3	“transcriptional regulation”
PFKFB3	“down-regulates quantity”	“β-D-fructose 6-phosphate”	“chemical modification”
IKBKB	“down-regulates activity”	PFKFB3	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 56 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
Activation of BAD and translocation to mitochondria	5	92.8×	2e-07
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	5	81.9×	2e-07
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	5	81.9×	2e-07
Activation of BH3-only proteins	5	60.5×	9e-07
RHO GTPases activate PKNs	5	38.7×	5e-06
Signaling by high-kinase activity BRAF mutants	5	38.7×	5e-06
Intrinsic Pathway for Apoptosis	5	35.7×	6e-06
MAP2K and MAPK activation	5	34.8×	7e-06

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	63
Likely benign	2
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1786 predictions. Top by Δscore:

Variant	Effect	Δscore
10:6203334:GAT:G	donor_gain	1.0000
10:6203337:G:GG	donor_gain	1.0000
10:6213612:T:TA	acceptor_gain	1.0000
10:6213618:TCCA:T	acceptor_loss	1.0000
10:6213619:CCAG:C	acceptor_loss	1.0000
10:6213620:CA:C	acceptor_loss	1.0000
10:6213621:A:AC	acceptor_loss	1.0000
10:6213621:A:AG	acceptor_gain	1.0000
10:6213621:AGCCT:A	acceptor_gain	1.0000
10:6213622:G:GA	acceptor_gain	1.0000
10:6213622:GC:G	acceptor_gain	1.0000
10:6213622:GCC:G	acceptor_gain	1.0000
10:6213622:GCCT:G	acceptor_gain	1.0000
10:6213622:GCCTG:G	acceptor_gain	1.0000
10:6213745:AAAG:A	donor_gain	1.0000
10:6213746:AAG:A	donor_gain	1.0000
10:6213747:AG:A	donor_gain	1.0000
10:6213747:AGG:A	donor_loss	1.0000
10:6213748:GG:G	donor_gain	1.0000
10:6213748:GGTG:G	donor_loss	1.0000
10:6213749:G:GG	donor_gain	1.0000
10:6215212:C:A	acceptor_gain	1.0000
10:6215217:ACAGT:A	acceptor_gain	1.0000
10:6215218:C:G	acceptor_gain	1.0000
10:6215219:A:AG	acceptor_gain	1.0000
10:6215219:A:T	acceptor_loss	1.0000
10:6215219:AGT:A	acceptor_gain	1.0000
10:6215220:G:GA	acceptor_gain	1.0000
10:6215220:GT:G	acceptor_gain	1.0000
10:6215220:GTG:G	acceptor_gain	1.0000

AlphaMissense

3419 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:6213670:G:C	G42R	1.000
10:6213692:C:T	T49I	1.000
10:6215245:G:C	R76P	1.000
10:6215280:T:C	F88L	1.000
10:6215282:C:A	F88L	1.000
10:6215282:C:G	F88L	1.000
10:6216142:C:A	A106D	1.000
10:6216723:T:A	N128K	1.000
10:6216723:T:G	N128K	1.000
10:6213656:T:A	V37D	0.999
10:6213671:G:A	G42D	0.999
10:6213677:C:A	P44H	0.999
10:6213680:C:A	A45D	0.999
10:6213683:G:C	R46P	0.999
10:6213685:G:C	G47R	0.999
10:6213685:G:T	G47C	0.999
10:6213686:G:A	G47D	0.999
10:6213686:G:T	G47V	0.999
10:6213688:A:C	K48Q	0.999
10:6213689:A:T	K48M	0.999
10:6213690:G:C	K48N	0.999
10:6213690:G:T	K48N	0.999
10:6213710:T:C	L55P	0.999
10:6213722:T:C	L59P	0.999
10:6213727:T:A	W61R	0.999
10:6213727:T:C	W61R	0.999
10:6215223:T:C	F69L	0.999
10:6215224:T:C	F69S	0.999
10:6215225:C:A	F69L	0.999
10:6215225:C:G	F69L	0.999

dbSNP variants (sampled 300 via entrez): RS1000021838 (10:6207547 C>T), RS1000030158 (10:6190676 T>A), RS1000077629 (10:6168822 G>A), RS1000083349 (10:6239548 A>G), RS1000103802 (10:6278075 A>G,T), RS1000113920 (10:6158141 T>C), RS1000130522 (10:6285619 T>C), RS1000152822 (10:6258633 T>A,C,G), RS1000158202 (10:6225890 C>T), RS1000165426 (10:6187302 A>G), RS1000208946 (10:6272998 C>T), RS1000216894 (10:6222872 C>A), RS1000218051 (10:6229255 C>T), RS1000222437 (10:6255399 C>A,T), RS1000269145 (10:6264582 C>G,T)

Disease associations

OMIM: gene MIM:605319 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

14 associations (top):

Study	Trait	p-value
GCST002520_4	Celiac disease	2.000000e-07
GCST002566_12	Response to chemotherapy in breast cancer hypertensive cases (cumulative dose) (bevacizumab)	9.000000e-06
GCST003814_11	Selective IgA deficiency	1.000000e-06
GCST004132_31	Crohn’s disease	2.000000e-08
GCST004640_4	Western dietary pattern	8.000000e-07
GCST004866_22	Alopecia areata	5.000000e-06
GCST005523_27	Celiac disease	2.000000e-08
GCST007245_1	Latent autoimmune diabetes	3.000000e-08
GCST007995_29	Asthma (childhood onset)	8.000000e-14
GCST008368_4	Plasma anti-thyroid peroxidase levels	1.000000e-06
GCST008916_1	Asthma	6.000000e-17
GCST009391_510	Metabolite levels	5.000000e-06
GCST009700_7	Obesity (extreme)	6.000000e-06
GCST009798_3	Asthma	1.000000e-17

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0005944	cumulative dose response to bevacizumab
EFO:0008111	diet measurement
EFO:0009706	latent autoimmune diabetes in adults
EFO:0010527	pyridoxate measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL2331053 (SINGLE PROTEIN), CHEMBL3832646 (PROTEIN COMPLEX)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 135 (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
CHEMBL4303611	PFK-158	1	135

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — Sugar phosphatases

Most potent curated ligand interactions (2 total), top 2:

Ligand	Action	Affinity	Parameter
PFKFB3 kinase Inhibitor 69	Inhibition	7.85	pIC50
PFK15	Inhibition	6.68	pIC50

Binding affinities (BindingDB)

41 measured of 41 human assays (41 total across all organisms); most potent 41 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
3-[(3-methyl-5-propan-2-yl-1-benzothiophen-2-yl)sulfonylamino]benzoic acid	IC50	30 nM	US-9233946: Sulfonamide compounds
3-methyl-5-propan-2-yl-N-[3-(2H-tetrazol-5-yl)phenyl]-1-benzofuran-2-sulfonamide	IC50	80 nM	US-9233946: Sulfonamide compounds
3,5-dimethyl-N-[3-(tetrazolidin-5-yl)phenyl]-1-benzothiophene-2-sulfonamide	IC50	130 nM	US-9233946: Sulfonamide compounds
3-[(5-chloro-3-methyl-1-benzothiophen-2-yl)sulfonylamino]benzoic acid	IC50	180 nM	US-9233946: Sulfonamide compounds
2-[3-[(3-methyl-5-propan-2-yl-1-benzothiophen-2-yl)sulfonylamino]phenyl]acetic acid	IC50	230 nM	US-9233946: Sulfonamide compounds
2,3,4-trichloro-N-[3-(tetrazolidin-5-yl)phenyl]benzenesulfonamide	IC50	280 nM	US-9233946: Sulfonamide compounds
3-[(3-methyl-5-propan-2-yl-1-benzofuran-2-yl)sulfonylamino]benzoic acid	IC50	280 nM	US-9233946: Sulfonamide compounds
3-methyl-N-[3-(2H-tetrazol-5-yl)phenyl]-1-benzothiophene-2-sulfonamide	IC50	280 nM	US-9233946: Sulfonamide compounds
5-(2-methyl-1,3-thiazol-4-yl)-N-[3-(2H-tetrazol-5-yl)phenyl]thiophene-2-sulfonamide	IC50	310 nM	US-9233946: Sulfonamide compounds
5-amino-3-methyl-N-[3-(2H-tetrazol-5-yl)phenyl]-1-benzothiophene-2-sulfonamide	IC50	360 nM	US-9233946: Sulfonamide compounds
3-(4-fluorophenyl)-N-[3-(2H-tetrazol-5-yl)phenyl]benzenesulfonamide	IC50	450 nM	US-9233946: Sulfonamide compounds
3-[5-[[3-(2H-tetrazol-5-yl)phenyl]sulfamoyl]thiophen-2-yl]benzamide	IC50	540 nM	US-9233946: Sulfonamide compounds
5-(5-chloro-1,2,4-thiadiazol-3-yl)-N-[3-(2H-tetrazol-5-yl)phenyl]thiophene-2-sulfonamide	IC50	560 nM	US-9233946: Sulfonamide compounds
4-chloro-N-[3-(2H-tetrazol-5-yl)phenyl]-2,1,3-benzoxadiazole-7-sulfonamide	IC50	570 nM	US-9233946: Sulfonamide compounds
4-methyl-2-[(3-methyl-5-propan-2-yl-1-benzothiophen-2-yl)sulfonylamino]-1,3-thiazole-5-carboxylic acid	IC50	610 nM	US-9233946: Sulfonamide compounds
5-(3,5-difluorophenyl)-N-[3-(2H-tetrazol-5-yl)phenyl]thiophene-2-sulfonamide	IC50	620 nM	US-9233946: Sulfonamide compounds
3-(4-methoxyphenyl)-N-[3-(2H-tetrazol-5-yl)phenyl]benzenesulfonamide	IC50	720 nM	US-9233946: Sulfonamide compounds
5-[(3-methyl-5-propan-2-yl-1-benzothiophen-2-yl)sulfonylamino]pyridine-3-carboxylic acid	IC50	730 nM	US-9233946: Sulfonamide compounds
6-[(3-methyl-5-propan-2-yl-1-benzothiophen-2-yl)sulfonylamino]pyridine-2-carboxylic acid	IC50	810 nM	US-9233946: Sulfonamide compounds
3-[(3-methyl-5-propan-2-yl-1-benzothiophen-2-yl)sulfonylamino]-5-nitrobenzoic acid	IC50	850 nM	US-9233946: Sulfonamide compounds
N-[3-(tetrazolidin-5-yl)phenyl]naphthalene-2-sulfonamide	IC50	850 nM	US-9233946: Sulfonamide compounds
2-[5-[3-[(3-methyl-5-propan-2-yl-1-benzothiophen-2-yl)sulfonylamino]phenyl]tetrazol-2-yl]acetic acid	IC50	1020 nM	US-9233946: Sulfonamide compounds
4-bromo-N-[3-(tetrazolidin-5-yl)phenyl]-2-(trifluoromethyl)benzenesulfonamide	IC50	1120 nM	US-9233946: Sulfonamide compounds
5-phenyl-N-[3-(2H-tetrazol-5-yl)phenyl]thiophene-2-sulfonamide	IC50	1300 nM	US-9233946: Sulfonamide compounds
4-phenyl-N-[3-(tetrazolidin-5-yl)phenyl]benzenesulfonamide	IC50	1390 nM	US-9233946: Sulfonamide compounds
N-[3-(tetrazolidin-5-yl)phenyl]-5-[3-(trifluoromethyl)phenyl]thiophene-2-sulfonamide	IC50	1420 nM	US-9233946: Sulfonamide compounds
2,4-dichloro-6-methyl-N-[3-(2H-tetrazol-5-yl)phenyl]benzenesulfonamide	IC50	1780 nM	US-9233946: Sulfonamide compounds
3-[[5-(2-methylsulfanylpyrimidin-4-yl)thiophen-2-yl]sulfonylamino]benzoic acid	IC50	2240 nM	US-9233946: Sulfonamide compounds
2,4,5-trichloro-N-[3-(tetrazolidin-5-yl)phenyl]benzenesulfonamide	IC50	2390 nM	US-9233946: Sulfonamide compounds
3-(3,5-dichlorophenyl)-N-[3-(2H-tetrazol-5-yl)phenyl]benzenesulfonamide	IC50	2540 nM	US-9233946: Sulfonamide compounds
4-(3,4-dichlorophenyl)-N-[3-(tetrazolidin-5-yl)phenyl]benzenesulfonamide	IC50	2800 nM	US-9233946: Sulfonamide compounds
3-[(3-phenylphenyl)sulfonylamino]benzoic acid	IC50	3100 nM	US-9233946: Sulfonamide compounds
5-(1,3-oxazol-5-yl)-N-[3-(tetrazolidin-5-yl)phenyl]thiophene-2-sulfonamide	IC50	3910 nM	US-9233946: Sulfonamide compounds
3-[(5-acetamido-3-methyl-1-benzothiophen-2-yl)sulfonylamino]benzoic acid	IC50	5070 nM	US-9233946: Sulfonamide compounds
3-[[5-chloro-4-(2-hydroxyphenyl)thiophen-2-yl]sulfonylamino]-2-hydroxybenzoic acid	IC50	5180 nM	US-9233946: Sulfonamide compounds
N-[3-(tetrazolidin-5-yl)phenyl]-3-[4-(trifluoromethyl)phenyl]benzenesulfonamide	IC50	5750 nM	US-9233946: Sulfonamide compounds
3-[[5-(1,2-oxazol-3-yl)thiophen-2-yl]sulfonylamino]benzoic acid	IC50	6310 nM	US-9233946: Sulfonamide compounds
3-[(5-pyridin-2-ylthiophen-2-yl)sulfonylamino]benzoic acid	IC50	6690 nM	US-9233946: Sulfonamide compounds
4-(1,3-oxazol-5-yl)-N-[3-(2H-tetrazol-5-yl)phenyl]benzenesulfonamide	IC50	8450 nM	US-9233946: Sulfonamide compounds
5-[(5-chloro-3-methyl-1-benzothiophen-2-yl)sulfonylamino]-2-hydroxybenzoic acid	IC50	9030 nM	US-9233946: Sulfonamide compounds
2-chloro-4-fluoro-N-[3-(2H-tetrazol-5-yl)phenyl]benzenesulfonamide	IC50	9840 nM	US-9233946: Sulfonamide compounds

ChEMBL bioactivities

452 potent at pChembl≥5 of 490 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.70	IC50	2	nM	CHEMBL4541928
8.52	IC50	3	nM	CHEMBL3422678
8.46	IC50	3.5	nM	CHEMBL5079257
8.46	IC50	3.5	nM	CHEMBL5078139
8.40	IC50	4	nM	CHEMBL3422677
8.40	IC50	4	nM	CHEMBL4592338
8.38	IC50	4.2	nM	CHEMBL5077027
8.38	IC50	4.2	nM	CHEMBL5273875
8.28	IC50	5.2	nM	CHEMBL5076616
8.19	IC50	6.5	nM	CHEMBL5078308
8.10	IC50	8	nM	CHEMBL3422674
8.10	IC50	8	nM	CHEMBL5076229
8.05	IC50	9	nM	CHEMBL4439789
8.00	IC50	9.9	nM	CHEMBL5079598
7.96	IC50	11	nM	CHEMBL3422676
7.96	IC50	11	nM	CHEMBL4465124
7.96	IC50	11	nM	CHEMBL4449586
7.85	IC50	14	nM	CHEMBL5092801
7.82	IC50	15	nM	CHEMBL4471955
7.77	IC50	17	nM	CHEMBL4542245
7.75	IC50	18	nM	CHEMBL4461874
7.70	IC50	20	nM	CHEMBL3422675
7.68	IC50	21	nM	CHEMBL3421731
7.66	IC50	22	nM	CHEMBL4470835
7.66	IC50	22	nM	CHEMBL4553861
7.66	IC50	22	nM	CHEMBL5093876
7.64	IC50	23	nM	CHEMBL3422651
7.64	IC50	23	nM	CHEMBL5083570
7.60	IC50	25	nM	CHEMBL5078139
7.58	IC50	26	nM	CHEMBL4518022
7.57	IC50	27	nM	CHEMBL3422673
7.55	IC50	28	nM	CHEMBL5084619
7.52	IC50	30	nM	CHEMBL3731843
7.52	IC50	30	nM	CHEMBL4437856
7.50	IC50	32	nM	CHEMBL5081217
7.48	IC50	33	nM	CHEMBL4459213
7.48	IC50	33	nM	CHEMBL4465233
7.48	IC50	33	nM	CHEMBL4538989
7.48	IC50	33	nM	CHEMBL5071836
7.46	IC50	35	nM	CHEMBL4438803
7.46	IC50	35	nM	CHEMBL5076430
7.44	IC50	36	nM	CHEMBL4576710
7.43	IC50	37	nM	CHEMBL5272308
7.42	IC50	38	nM	CHEMBL4472403
7.42	IC50	38	nM	CHEMBL4539068
7.39	IC50	41	nM	CHEMBL4442954
7.36	IC50	44	nM	CHEMBL5093213
7.33	IC50	47	nM	CHEMBL5286061
7.32	IC50	48	nM	CHEMBL3422672
7.31	IC50	49	nM	CHEMBL4458729

PubChem BioAssay actives

154 with measured affinity, of 264 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-[[8-(1-methylindol-6-yl)quinoxalin-6-yl]amino]-N-(1-methylpiperidin-3-yl)pyridine-4-carboxamide	1536366: Inhibition of recombinant human His-tagged PFKFB3 expressed in Escherichia coli using fructose-6-phosphate as substrate measured after 2 hrs by ADP-Glo assay	ic50	0.0020	uM
(2S)-N-[4-[3-cyano-1-[(3,5-dimethyl-1,2-oxazol-4-yl)methyl]indazol-5-yl]oxyphenyl]pyrrolidine-2-carboxamide	1203858: Inhibition of recombinant human PFKFB3 using fructose 6 phosphate as substrate assessed as ADP generation after 1 hr by ADP Glo assay	ic50	0.0030	uM
N-[(6-methoxy-3-pyridinyl)-(3-methyltriazol-4-yl)methyl]-8-(1-methylindol-6-yl)quinoxalin-6-amine	1927412: Inhibition of PFKFB3 (unknown origin) incubated for 90 mins by ADP-Glo luminescent assay	ic50	0.0035	uM
(2S)-N-[4-[3-cyano-1-(2-methylpropyl)indazol-5-yl]oxyphenyl]pyrrolidine-2-carboxamide	1203858: Inhibition of recombinant human PFKFB3 using fructose 6 phosphate as substrate assessed as ADP generation after 1 hr by ADP Glo assay	ic50	0.0040	uM
3-[[8-(3-methyl-1-benzothiophen-5-yl)quinoxalin-6-yl]amino]-N-[(3R)-1-methylpyrrolidin-3-yl]pyridine-4-carboxamide	1536366: Inhibition of recombinant human His-tagged PFKFB3 expressed in Escherichia coli using fructose-6-phosphate as substrate measured after 2 hrs by ADP-Glo assay	ic50	0.0040	uM
8-(3-methyl-1-benzofuran-5-yl)-N-[(S)-(1-methylpyrazol-4-yl)-(3-methyltriazol-4-yl)methyl]quinoxalin-6-amine	1927412: Inhibition of PFKFB3 (unknown origin) incubated for 90 mins by ADP-Glo luminescent assay	ic50	0.0042	uM
8-(1-methylindol-6-yl)-N-[(S)-(1-methylpyrazol-4-yl)-(3-methyltriazol-4-yl)methyl]quinoxalin-6-amine	1927412: Inhibition of PFKFB3 (unknown origin) incubated for 90 mins by ADP-Glo luminescent assay	ic50	0.0052	uM
(2S)-N-[4-[3-cyano-1-(2-methyl-1-oxo-3H-isoindol-5-yl)indol-5-yl]oxyphenyl]pyrrolidine-2-carboxamide	1203858: Inhibition of recombinant human PFKFB3 using fructose 6 phosphate as substrate assessed as ADP generation after 1 hr by ADP Glo assay	ic50	0.0080	uM
3-[[8-(3-methyl-1-benzothiophen-5-yl)quinoxalin-6-yl]amino]-N-[(3S)-1-methylpyrrolidin-3-yl]pyridine-4-carboxamide	1536366: Inhibition of recombinant human His-tagged PFKFB3 expressed in Escherichia coli using fructose-6-phosphate as substrate measured after 2 hrs by ADP-Glo assay	ic50	0.0090	uM
N-(1-acetylpiperidin-3-yl)-3-[[8-(1-methylindol-6-yl)quinoxalin-6-yl]amino]pyridine-4-carboxamide	1536366: Inhibition of recombinant human His-tagged PFKFB3 expressed in Escherichia coli using fructose-6-phosphate as substrate measured after 2 hrs by ADP-Glo assay	ic50	0.0110	uM
2-[[8-(1-methylindol-6-yl)quinoxalin-6-yl]amino]-N-[(1-methylpyrrolidin-3-yl)methyl]benzenesulfonamide	1536366: Inhibition of recombinant human His-tagged PFKFB3 expressed in Escherichia coli using fructose-6-phosphate as substrate measured after 2 hrs by ADP-Glo assay	ic50	0.0110	uM
(2S)-N-[4-[3-cyano-1-[(3,5-dimethyl-1,2-oxazol-4-yl)methyl]indol-5-yl]oxyphenyl]pyrrolidine-2-carboxamide	1203858: Inhibition of recombinant human PFKFB3 using fructose 6 phosphate as substrate assessed as ADP generation after 1 hr by ADP Glo assay	ic50	0.0110	uM
3-[[8-(1-methylindol-6-yl)quinoxalin-6-yl]amino]-N-(1-methylpyrrolidin-3-yl)pyridine-4-carboxamide	1536366: Inhibition of recombinant human His-tagged PFKFB3 expressed in Escherichia coli using fructose-6-phosphate as substrate measured after 2 hrs by ADP-Glo assay	ic50	0.0150	uM
3-[[8-(4-fluoro-1-methylindol-6-yl)quinoxalin-6-yl]amino]-N-(1-methylpyrrolidin-3-yl)pyridine-4-carboxamide	1536366: Inhibition of recombinant human His-tagged PFKFB3 expressed in Escherichia coli using fructose-6-phosphate as substrate measured after 2 hrs by ADP-Glo assay	ic50	0.0170	uM
N-(1-acetylpiperidin-4-yl)-3-[[8-(1-methylindol-6-yl)quinoxalin-6-yl]amino]pyridine-4-carboxamide	1536366: Inhibition of recombinant human His-tagged PFKFB3 expressed in Escherichia coli using fructose-6-phosphate as substrate measured after 2 hrs by ADP-Glo assay	ic50	0.0180	uM
(2S)-N-[4-(1-benzyl-3-cyanoindol-5-yl)oxyphenyl]pyrrolidine-2-carboxamide	1203858: Inhibition of recombinant human PFKFB3 using fructose 6 phosphate as substrate assessed as ADP generation after 1 hr by ADP Glo assay	ic50	0.0200	uM
(2S)-N-[4-[1-methyl-3-(1-methylpyrazol-4-yl)indol-5-yl]oxyphenyl]pyrrolidine-2-carboxamide	1203858: Inhibition of recombinant human PFKFB3 using fructose 6 phosphate as substrate assessed as ADP generation after 1 hr by ADP Glo assay	ic50	0.0210	uM
3-[[8-(1-methylindol-6-yl)quinoxalin-6-yl]amino]-N-pyrimidin-5-ylpyridine-4-carboxamide	1536366: Inhibition of recombinant human His-tagged PFKFB3 expressed in Escherichia coli using fructose-6-phosphate as substrate measured after 2 hrs by ADP-Glo assay	ic50	0.0220	uM
2-[[8-(1-methylindol-6-yl)quinoxalin-6-yl]amino]-N-(pyrimidin-5-ylmethyl)benzenesulfonamide	1536366: Inhibition of recombinant human His-tagged PFKFB3 expressed in Escherichia coli using fructose-6-phosphate as substrate measured after 2 hrs by ADP-Glo assay	ic50	0.0220	uM
(2S)-N-[4-[3-cyano-1-(2-methylpropyl)indol-5-yl]oxyphenyl]pyrrolidine-2-carboxamide	1203858: Inhibition of recombinant human PFKFB3 using fructose 6 phosphate as substrate assessed as ADP generation after 1 hr by ADP Glo assay	ic50	0.0230	uM
2-[[8-(1-methylindol-6-yl)quinoxalin-6-yl]amino]-N-(oxan-4-ylmethyl)benzenesulfonamide	1536366: Inhibition of recombinant human His-tagged PFKFB3 expressed in Escherichia coli using fructose-6-phosphate as substrate measured after 2 hrs by ADP-Glo assay	ic50	0.0260	uM
(2S)-N-[4-(3-cyano-1-phenylindol-5-yl)oxyphenyl]pyrrolidine-2-carboxamide	1203858: Inhibition of recombinant human PFKFB3 using fructose 6 phosphate as substrate assessed as ADP generation after 1 hr by ADP Glo assay	ic50	0.0270	uM
N-(1-methylazetidin-3-yl)-3-[[8-(1-methylindol-6-yl)quinoxalin-6-yl]amino]pyridine-4-carboxamide	1536366: Inhibition of recombinant human His-tagged PFKFB3 expressed in Escherichia coli using fructose-6-phosphate as substrate measured after 2 hrs by ADP-Glo assay	ic50	0.0300	uM
3-[(3-methyl-5-propan-2-yl-1-benzothiophen-2-yl)sulfonylamino]benzoic acid	1927401: Inhibition of PFKFB3 (unknown origin) by ADP-Glo luminescent assay	ic50	0.0300	uM
3-[[8-(1-methylindol-6-yl)quinoxalin-6-yl]amino]-N-(1-methylpyrazol-4-yl)pyridine-4-carboxamide	1536366: Inhibition of recombinant human His-tagged PFKFB3 expressed in Escherichia coli using fructose-6-phosphate as substrate measured after 2 hrs by ADP-Glo assay	ic50	0.0330	uM
2-[[8-(1-methylindol-6-yl)quinoxalin-6-yl]amino]-N-(1-methylpyrrolidin-3-yl)benzenesulfonamide	1536366: Inhibition of recombinant human His-tagged PFKFB3 expressed in Escherichia coli using fructose-6-phosphate as substrate measured after 2 hrs by ADP-Glo assay	ic50	0.0330	uM
3-[[8-(1-methylindol-6-yl)quinoxalin-6-yl]amino]-N-(morpholin-3-ylmethyl)pyridine-4-carboxamide	1536366: Inhibition of recombinant human His-tagged PFKFB3 expressed in Escherichia coli using fructose-6-phosphate as substrate measured after 2 hrs by ADP-Glo assay	ic50	0.0330	uM
3-[[8-(2-amino-1,3-benzothiazol-5-yl)quinoxalin-6-yl]amino]-N-(1-methylpyrrolidin-3-yl)pyridine-4-carboxamide	1536366: Inhibition of recombinant human His-tagged PFKFB3 expressed in Escherichia coli using fructose-6-phosphate as substrate measured after 2 hrs by ADP-Glo assay	ic50	0.0350	uM
8-(1-methylindol-6-yl)-N-(2-morpholin-4-ylsulfonylphenyl)quinoxalin-6-amine	1536366: Inhibition of recombinant human His-tagged PFKFB3 expressed in Escherichia coli using fructose-6-phosphate as substrate measured after 2 hrs by ADP-Glo assay	ic50	0.0360	uM
8-(1-methylindol-6-yl)-N-(4-methylsulfonyl-3-pyridinyl)quinoxalin-6-amine	1927414: Inhibition of human recombinant His-tagged PFKFB3 expressed in Escherichia coli using Fructose-6-phosphate incubated for 2 hrs in presence of ATP by ADP-Glo assay	ic50	0.0370	uM
3-[[8-(1-methylindol-6-yl)quinoxalin-6-yl]amino]-N-(1-methylpiperidin-4-yl)pyridine-4-carboxamide	1536366: Inhibition of recombinant human His-tagged PFKFB3 expressed in Escherichia coli using fructose-6-phosphate as substrate measured after 2 hrs by ADP-Glo assay	ic50	0.0380	uM
2-[[8-(1-methylindol-6-yl)quinoxalin-6-yl]amino]-N-[(1-methylpyrazol-4-yl)methyl]benzenesulfonamide	1536366: Inhibition of recombinant human His-tagged PFKFB3 expressed in Escherichia coli using fructose-6-phosphate as substrate measured after 2 hrs by ADP-Glo assay	ic50	0.0380	uM
3-[[8-(1-methylindol-6-yl)quinoxalin-6-yl]amino]-N-(1-methyl-2-oxopiperidin-4-yl)pyridine-4-carboxamide	1536366: Inhibition of recombinant human His-tagged PFKFB3 expressed in Escherichia coli using fructose-6-phosphate as substrate measured after 2 hrs by ADP-Glo assay	ic50	0.0410	uM
3-[[8-(1-methylindol-6-yl)quinoxalin-6-yl]amino]-N-(oxan-4-yl)pyridine-4-carboxamide	1927414: Inhibition of human recombinant His-tagged PFKFB3 expressed in Escherichia coli using Fructose-6-phosphate incubated for 2 hrs in presence of ATP by ADP-Glo assay	ic50	0.0470	uM
(2S)-N-[4-[3-cyano-1-(oxan-4-ylmethyl)indol-5-yl]oxyphenyl]pyrrolidine-2-carboxamide	1203858: Inhibition of recombinant human PFKFB3 using fructose 6 phosphate as substrate assessed as ADP generation after 1 hr by ADP Glo assay	ic50	0.0480	uM
3-[[8-(1-methylindol-6-yl)quinoxalin-6-yl]amino]pyridine-4-carboxamide	1536366: Inhibition of recombinant human His-tagged PFKFB3 expressed in Escherichia coli using fructose-6-phosphate as substrate measured after 2 hrs by ADP-Glo assay	ic50	0.0490	uM
2-[[8-(1-methylindol-6-yl)quinoxalin-6-yl]amino]-N-(1-methylpiperidin-3-yl)benzenesulfonamide	1536366: Inhibition of recombinant human His-tagged PFKFB3 expressed in Escherichia coli using fructose-6-phosphate as substrate measured after 2 hrs by ADP-Glo assay	ic50	0.0590	uM
N-methyl-2-[[8-(1-methylindol-6-yl)quinoxalin-6-yl]amino]-N-(pyrimidin-5-ylmethyl)benzenesulfonamide	1536366: Inhibition of recombinant human His-tagged PFKFB3 expressed in Escherichia coli using fructose-6-phosphate as substrate measured after 2 hrs by ADP-Glo assay	ic50	0.0620	uM
3-[[8-(1-methylindol-6-yl)quinoxalin-6-yl]amino]-N-(2-oxopiperidin-4-yl)pyridine-4-carboxamide	1536366: Inhibition of recombinant human His-tagged PFKFB3 expressed in Escherichia coli using fructose-6-phosphate as substrate measured after 2 hrs by ADP-Glo assay	ic50	0.0690	uM
N-(1-acetylazetidin-3-yl)-3-[[8-(1-methylindol-6-yl)quinoxalin-6-yl]amino]pyridine-4-carboxamide	1536366: Inhibition of recombinant human His-tagged PFKFB3 expressed in Escherichia coli using fructose-6-phosphate as substrate measured after 2 hrs by ADP-Glo assay	ic50	0.0730	uM
3-[[8-(1-methylindol-6-yl)quinoxalin-6-yl]amino]-N-[(1-methylpyrrolidin-3-yl)methyl]pyridine-4-carboxamide	1536366: Inhibition of recombinant human His-tagged PFKFB3 expressed in Escherichia coli using fructose-6-phosphate as substrate measured after 2 hrs by ADP-Glo assay	ic50	0.0740	uM
(2S)-N-[4-[[3-cyano-1-(2-methylpropyl)indol-5-yl]-methylamino]phenyl]pyrrolidine-2-carboxamide	1203858: Inhibition of recombinant human PFKFB3 using fructose 6 phosphate as substrate assessed as ADP generation after 1 hr by ADP Glo assay	ic50	0.0750	uM
3-methyl-5-propan-2-yl-N-[3-(2H-tetrazol-5-yl)phenyl]-1-benzofuran-2-sulfonamide	1927401: Inhibition of PFKFB3 (unknown origin) by ADP-Glo luminescent assay	ic50	0.0800	uM
N-methyl-3-[[8-(1-methylindol-6-yl)quinoxalin-6-yl]amino]pyridine-4-carboxamide	1536366: Inhibition of recombinant human His-tagged PFKFB3 expressed in Escherichia coli using fructose-6-phosphate as substrate measured after 2 hrs by ADP-Glo assay	ic50	0.0830	uM
8-(1-methylindol-6-yl)-N-(2-methylsulfonylphenyl)quinoxalin-6-amine	1536366: Inhibition of recombinant human His-tagged PFKFB3 expressed in Escherichia coli using fructose-6-phosphate as substrate measured after 2 hrs by ADP-Glo assay	ic50	0.0850	uM
(2S)-N-[4-(3-cyano-1-ethylindol-5-yl)oxyphenyl]azetidine-2-carboxamide	1203858: Inhibition of recombinant human PFKFB3 using fructose 6 phosphate as substrate assessed as ADP generation after 1 hr by ADP Glo assay	ic50	0.0860	uM
2-hydroxyethyl 4-[[3-(5-fluoro-2-hydroxyphenyl)phenyl]sulfonylamino]-2-hydroxybenzoate	1927415: Inhibition of PFKFB3 in human NUGC-3 cells assessed as reduction in Fructose-2,6-Bisphosphate production	ic50	0.0900	uM
N-[(4-acetylmorpholin-2-yl)methyl]-3-[[8-(1-methylindol-6-yl)quinoxalin-6-yl]amino]pyridine-4-carboxamide	1536366: Inhibition of recombinant human His-tagged PFKFB3 expressed in Escherichia coli using fructose-6-phosphate as substrate measured after 2 hrs by ADP-Glo assay	ic50	0.0930	uM
N,N-dimethyl-2-[[8-(1-methylindol-6-yl)quinoxalin-6-yl]amino]benzenesulfonamide	1536366: Inhibition of recombinant human His-tagged PFKFB3 expressed in Escherichia coli using fructose-6-phosphate as substrate measured after 2 hrs by ADP-Glo assay	ic50	0.0940	uM
ethyl 7-hydroxy-2-oxochromene-3-carboxylate	1927422: Binding affinity to PFKFB3 (unknown origin)	ki	0.0940	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases abundance, increases expression, affects expression, decreases expression, affects cotreatment	5
Oxygen	increases reaction, increases expression	5
cobaltous chloride	increases expression, decreases reaction	4
Arsenic	affects methylation, decreases expression, increases abundance, increases expression, affects cotreatment	4
Tretinoin	increases expression	4
Cyclosporine	decreases expression	4
Air Pollutants	increases abundance, affects expression, decreases expression, affects cotreatment	3
Estradiol	decreases expression, increases expression	3
Silicon Dioxide	decreases reaction, increases expression, decreases expression	3
bisphenol A	affects expression, affects cotreatment, increases methylation	2
Ethanol	affects cotreatment, increases expression, decreases expression	2
Benzo(a)pyrene	affects methylation, decreases methylation	2
Ozone	increases abundance, affects expression, affects cotreatment, decreases expression	2
Quercetin	decreases expression, increases expression	2
Tobacco Smoke Pollution	increases expression	2
Valproic Acid	increases methylation, increases expression	2
Cadmium Chloride	decreases reaction, increases abundance, increases expression	2
aristolochic acid I	decreases expression	1
N-(1,2,3,5,6,7-hexahydro-S-indacen-4-ylcarbamoyl)-4-(2-hydroxy-2-propanyl)-2-furansulfonamide	increases expression, decreases reaction	1
FR900359	decreases phosphorylation	1
4-hydroxyphenyl 4-isopropoxyphenylsulfone	decreases expression	1
PF-06840003	decreases expression, decreases reaction	1
aminomethylphosphonic acid (AMPA)	increases expression	1
quinone	affects cotreatment, increases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, decreases expression, increases abundance	1
sodium arsenate	increases abundance, increases expression	1
salinomycin	decreases expression	1
beta-lapachone	decreases expression, increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1

ChEMBL screening assays

52 unique, capped per target: 52 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2343949	Binding	Inhibition of IPFK2 (unknown origin)	Discovery of a novel class of highly potent, selective, ATP-competitive, and orally bioavailable inhibitors of the mammalian target of rapamycin (mTOR). — J Med Chem

Cellosaurus cell lines

9 cell lines: 8 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D1Y9	Abcam A-549 PFKFB3 KO	Cancer cell line	Male
CVCL_D2CG	Abcam HCT 116 PFKFB3 KO	Cancer cell line	Male
CVCL_D7WT	Ubigene A-549 PFKFB3 KO	Cancer cell line	Male
CVCL_D8S6	Ubigene HCT 116 PFKFB3 KO	Cancer cell line	Male
CVCL_D9MM	Ubigene HEK293 PFKFB3 KO	Transformed cell line	Female
CVCL_E0JZ	Ubigene HeLa PFKFB3 KO	Cancer cell line	Female
CVCL_E0VW	Ubigene Huh-7 PFKFB3 KO	Cancer cell line	Male
CVCL_TC95	HAP1 PFKFB3 (-) 1	Cancer cell line	Male
CVCL_TC96	HAP1 PFKFB3 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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