KHK

Summary

KHK (ketohexokinase, HGNC:6315) is a protein-coding gene on chromosome 2p23.3, encoding Ketohexokinase (P50053). Catalyzes the phosphorylation of the ketose sugar fructose to fructose-1-phosphate.

This gene encodes ketohexokinase that catalyzes conversion of fructose to fructose-1-phosphate. The product of this gene is the first enzyme with a specialized pathway that catabolizes dietary fructose. Alternatively spliced transcript variants encoding different isoforms have been identified.

Source: NCBI Gene 3795 — RefSeq curated summary.

At a glance

• Gene–disease (curated): essential fructosuria (Moderate, GenCC)
• GWAS associations: 8
• Clinical variants (ClinVar): 81 total — 1 pathogenic
• Phenotypes (HPO): 8
• Druggable target: yes — 2 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_006488

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6315
Approved symbol	KHK
Name	ketohexokinase
Location	2p23.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000138030
Ensembl biotype	protein_coding
OMIM	614058
Entrez	3795

Gene structure

Transcript identifiers

Ensembl transcripts: 28 — 25 protein_coding, 2 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000260598, ENST00000260599, ENST00000429697, ENST00000464371, ENST00000469936, ENST00000490823, ENST00000908271, ENST00000908272, ENST00000908273, ENST00000908274, ENST00000908275, ENST00000908276, ENST00000908277, ENST00000908278, ENST00000908279, ENST00000908280, ENST00000908281, ENST00000908282, ENST00000908283, ENST00000908284, ENST00000908285, ENST00000908286, ENST00000908287, ENST00000908288, ENST00000913877, ENST00000913878, ENST00000968340, ENST00000968341

RefSeq mRNA: 2 — MANE Select: NM_006488 NM_000221, NM_006488

CCDS: CCDS1734, CCDS1735

Canonical transcript exons

ENST00000260598 — 8 exons

Exon	Start	End
ENSE00000932386	27094800	27094934
ENSE00001880745	27099665	27100762
ENSE00001938617	27086772	27087351
ENSE00003476126	27096729	27096801
ENSE00003570114	27092332	27092448
ENSE00003589618	27097503	27097649
ENSE00003592939	27099196	27099284
ENSE00003631037	27099420	27099577

Expression profiles

Bgee: expression breadth ubiquitous, 213 present calls, max score 99.30.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 3.5972 / max 260.2797, expressed in 1033 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
19321	2.6776	1012
19323	0.6564	61
19322	0.2631	48

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	99.30	gold quality
liver	UBERON:0002107	97.51	gold quality
ileal mucosa	UBERON:0000331	97.10	gold quality
adult mammalian kidney	UBERON:0000082	96.59	gold quality
jejunal mucosa	UBERON:0000399	96.52	gold quality
duodenum	UBERON:0002114	96.50	gold quality
nephron tubule	UBERON:0001231	94.76	gold quality
small intestine Peyer’s patch	UBERON:0003454	94.24	gold quality
small intestine	UBERON:0002108	93.68	gold quality
kidney epithelium	UBERON:0004819	93.48	gold quality
kidney	UBERON:0002113	92.00	gold quality
renal glomerulus	UBERON:0000074	91.75	gold quality
metanephric glomerulus	UBERON:0004736	91.49	gold quality
cortex of kidney	UBERON:0001225	90.68	gold quality
adult organism	UBERON:0007023	90.67	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	88.08	gold quality
mucosa of transverse colon	UBERON:0004991	87.10	gold quality
right hemisphere of cerebellum	UBERON:0014890	86.28	gold quality
cerebellar hemisphere	UBERON:0002245	85.53	gold quality
cerebellar cortex	UBERON:0002129	85.39	gold quality
metanephros	UBERON:0000081	85.33	gold quality
jejunum	UBERON:0002115	85.30	gold quality
renal medulla	UBERON:0000362	84.99	gold quality
prefrontal cortex	UBERON:0000451	84.81	gold quality
pancreatic ductal cell	CL:0002079	84.71	silver quality
cerebellum	UBERON:0002037	84.26	gold quality
metanephros cortex	UBERON:0010533	83.84	gold quality
body of pancreas	UBERON:0001150	83.35	gold quality
right frontal lobe	UBERON:0002810	83.12	gold quality
left adrenal gland cortex	UBERON:0035825	82.35	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-GEOD-125970	yes	1158.75
E-CURD-135	no	425.23
E-MTAB-7008	no	208.55
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MLXIPL

miRNA regulators (miRDB)

41 targeting KHK, 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-302E	99.96	70.74	2669
HSA-MIR-302A-3P	99.89	71.23	1777
HSA-MIR-302B-3P	99.89	71.23	1777
HSA-MIR-302C-3P	99.89	71.20	1778
HSA-MIR-302D-3P	99.89	71.25	1777
HSA-MIR-12119	99.87	68.35	1653
HSA-MIR-3151-5P	99.86	63.83	1069
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-6836-5P	99.60	65.62	1538
HSA-MIR-6132	99.60	65.83	1554
HSA-MIR-4649-3P	99.56	66.90	1783
HSA-MIR-491-5P	99.13	65.98	1468
HSA-MIR-1304-5P	98.90	68.58	1054
HSA-MIR-129-1-3P	98.86	68.41	779
HSA-MIR-129-2-3P	98.86	68.41	779
HSA-MIR-760	98.81	66.65	1392
HSA-MIR-655-5P	98.74	65.93	888
HSA-MIR-1301-3P	98.64	68.27	1071
HSA-MIR-5047	98.64	68.62	1035
HSA-MIR-218-1-3P	98.63	67.97	832
HSA-MIR-9903	98.47	66.70	748
HSA-MIR-3187-5P	98.36	65.74	1776
HSA-MIR-653-3P	98.31	67.71	1542
HSA-MIR-3155A	98.16	66.09	965
HSA-MIR-3155B	98.16	66.09	965
HSA-MIR-484	98.16	66.92	1074
HSA-MIR-6511A-5P	98.13	67.47	1770
HSA-MIR-4303	98.01	68.13	2304
HSA-MIR-450A-2-3P	97.91	67.56	1459

Literature-anchored findings (GeneRIF, showing 18)

• ketohexokinase-A serves an unknown physiologic function that remains intact in essential fructosuria. (PMID:12941785)
• The expression of ketohexokinase is diminished in human clear cell type of renal cell carcinoma (PMID:16372272)
• Ketohexokinase-dependent metabolism of fructose induces proinflammatory mediators in proximal tubular cells. (PMID:19158351)
• The structure of the KHK-A ternary complex revealed an active site with fructose & the ATP analogue in positions ready for phosphorylation. The effects of the pathogenic mutations Gly40Arg & Ala43Thr have been modelled in the context of the KHK structure. (PMID:19237742)
• In human hepatocytes uric acid up-regulates KHK expression thus leading to the amplification of the lipogenic effects of fructose. (PMID:23112875)
• This study determined if single nucleotide polymorphisms in genes involved in fructose transport,SLC2A2 and SLC2A5 and metabolism, etohexokinase affect inter-individual variability in metabolic phenotypes. (PMID:23341889)
• These studies identify fructokinase as a novel mediator of diabetic nephropathy and document a novel role for endogenous fructose production, or fructoneogenesis, in driving renal disease. (PMID:24876114)
• myocardial hypoxia actuates fructose metabolism in human and mouse models of pathological cardiac hypertrophy through hypoxia-inducible factor 1alpha (HIF1alpha) activation of SF3B1 and SF3B1-mediated splice switching of KHK-A to KHK-C (PMID:26083752)
• compared with normal hepatocytes, hepatocellular carcinoma (HCC) cells markedly reduce the rate of fructose metabolism and the level of reactive oxygen species, as a result of a c-Myc-dependent and heterogeneous nuclear ribonucleoprotein (hnRNP) H1- and H2-mediated switch from expression of the high-activity fructokinase (KHK)-C to the low-activity KHK-A isoform. (PMID:27088854)
• Angelica archangelica, Garcinia mangostana, Petroselinum crispum, and Scutellaria baicalensis were the top four botanical candidiates identified with inhibitory activity against ketohexokinase-C. (PMID:27322374)
• Data indicate metabolic enzymes NAD kinase and ketohexokinase as candidate metabolic gene targets, and the chromatin remodeling protein INO80C as a tumor suppressor in KRAS(MUT) colorectal tumor xenograft. (PMID:28954733)
• KHK-A has a role in antioxidative stress and hepatocellular carcinoma development that involves phosphorylating p62 (PMID:31032410)
• KHK-A promotes the proliferation of oesophageal squamous cell carcinoma through the up-regulation of PRPS1. (PMID:32928708)
• Ketohexokinase-A acts as a nuclear protein kinase that mediates fructose-induced metastasis in breast cancer. (PMID:33116123)
• Prevalence and cardiometabolic correlates of ketohexokinase gene variants among UK Biobank participants. (PMID:33621267)
• USP36 promotes tumor growth of non-small cell lung cancer via increasing KHK-A expression by regulating c-MYC-hnRNPH1/H2 axis. (PMID:35133629)
• GLUT5-KHK axis-mediated fructose metabolism drives proliferation and chemotherapy resistance of colorectal cancer. (PMID:35257833)
• Fructose induced KHK-C can increase ER stress independent of its effect on lipogenesis to drive liver disease in diet-induced and genetic models of NAFLD. (PMID:37230214)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	khk	ENSDARG00000029874
mus_musculus	Khk	ENSMUSG00000029162
rattus_norvegicus	Khk	ENSRNOG00000008047
drosophila_melanogaster	CG12289	FBGN0036160
drosophila_melanogaster	CG7551	FBGN0036161
drosophila_melanogaster	CG7335	FBGN0036941
drosophila_melanogaster	CG7328	FBGN0036942

Paralogs (3): ADK (ENSG00000156110), RBKS (ENSG00000171174), TMEM256 (ENSG00000205544)

Protein

Protein identifiers

Ketohexokinase — P50053 (reviewed: P50053)

Alternative names: Hepatic fructokinase

All UniProt accessions (3): P50053, A0A140VJM6, C9JDL1

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the phosphorylation of the ketose sugar fructose to fructose-1-phosphate.

Subunit / interactions. Homodimer.

Tissue specificity. Most abundant in liver, kidney, gut, spleen and pancreas. Low levels also found in adrenal, muscle, brain and eye.

Disease relevance. Fructosuria (FRUCT) [MIM:229800] Benign defect of intermediary metabolism. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Requires potassium. Inhibition by ADP.

Pathway. Carbohydrate metabolism; fructose metabolism.

Miscellaneous. More widely distributed but with a low expression level. KM=7 mM for D-fructose (at 25 degrees Celsius). KM=036 mM for Mg-ATP (at 25 degrees Celsius). kcat is 6.9 sec(-1).

Similarity. Belongs to the carbohydrate kinase PfkB family.

Isoforms (2)

UniProt ID	Names	Canonical?
P50053-1	C, Central, hepatic/renal/intestinal	yes
P50053-2	A, Peripheral

RefSeq proteins (2): NP_000212, NP_006479* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR011611	PfkB_dom	Domain
IPR029056	Ribokinase-like	Homologous_superfamily
IPR034093	KHK	Family
IPR052562	Ketohexokinase-related	Family

Pfam: PF00294

Enzyme classification (BRENDA):

• EC 2.7.1.3 — ketohexokinase (BRENDA: 10 organisms, 57 substrates, 98 inhibitors, 55 Km, 12 kcat entries)

Substrate kinetics (BRENDA)

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

Substrate	Km (mM)	Measurements
D-FRUCTOSE	0.1–8.2	11
ATP	0.15–3.3	10
L-SORBOSE	0.4–19.3	4
2,5-ANHYDRO-D-GLUCITOL	2.9–47	3
2,5-ANHYDRO-D-MANNITOL	1.6–6.3	3
2,5-ANHYDRO-D-MANNOSE	0.31–1.5	3
D-RIBOSE	142–434	3
D-XYLOSE	0.44–1.4	3
2,5-ANHYDRO-D-LYXITOL	10–67	2
D-RIBULOSE	1.8–32.7	2
D-TAGATOSE	0.9	2
5-KETO-D-FRUCTOSE	1.2	1
D-MANNOHEPTULOSE	120	1
D-PSICOSE	11	1
D-RIBONO-GAMMA-LACTONE	58	1

Catalyzed reactions (Rhea), 1 shown:

• beta-D-fructose + ATP = beta-D-fructose 1-phosphate + ADP + H(+) (RHEA:18145)

UniProt features (44 total): strand 16, helix 14, binding site 8, sequence variant 3, chain 1, turn 1, splice variant 1

Structure

Experimental structures (PDB)

38 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
9FHD	X-RAY DIFFRACTION	1.84
2HLZ	X-RAY DIFFRACTION	1.85
2HQQ	X-RAY DIFFRACTION	1.86
9Z29	X-RAY DIFFRACTION	1.97
8OMJ	X-RAY DIFFRACTION	1.98
8UG1	X-RAY DIFFRACTION	1.99
8OME	X-RAY DIFFRACTION	2
9Z2A	X-RAY DIFFRACTION	2
8UG3	X-RAY DIFFRACTION	2.02
9Z2C	X-RAY DIFFRACTION	2.02
2HW1	X-RAY DIFFRACTION	2.1
9Z2B	X-RAY DIFFRACTION	2.11
8OMF	X-RAY DIFFRACTION	2.14
9Z28	X-RAY DIFFRACTION	2.15
5WBM	X-RAY DIFFRACTION	2.16
5WBO	X-RAY DIFFRACTION	2.25
3NBV	X-RAY DIFFRACTION	2.3
6UL7	X-RAY DIFFRACTION	2.3
6W0Z	X-RAY DIFFRACTION	2.3
9FHE	X-RAY DIFFRACTION	2.31
3NBW	X-RAY DIFFRACTION	2.34
6W0X	X-RAY DIFFRACTION	2.38
3NC9	X-RAY DIFFRACTION	2.4
5WBQ	X-RAY DIFFRACTION	2.4
5WBZ	X-RAY DIFFRACTION	2.4
6W0N	X-RAY DIFFRACTION	2.41
8OMK	X-RAY DIFFRACTION	2.48
3NC2	X-RAY DIFFRACTION	2.5
3QA2	X-RAY DIFFRACTION	2.52
6W0Y	X-RAY DIFFRACTION	2.54

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P50053-F1	97.32	0.97

Functional residue map

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

Ligand- & substrate-binding residues (8): 15; 41; 42; 45; 108; 226–229; 255–258; 258

Function

Pathways and Gene Ontology

Reactome pathways

8 pathways

ID	Pathway
R-HSA-5657562	Essential fructosuria
R-HSA-70350	Fructose catabolism
R-HSA-1430728	Metabolism
R-HSA-1643685	Disease
R-HSA-5652084	Fructose metabolism
R-HSA-5663084	Diseases of carbohydrate metabolism
R-HSA-5668914	Diseases of metabolism
R-HSA-71387	Metabolism of carbohydrates and carbohydrate derivatives

MSigDB gene sets: 192 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_DN, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, MORF_MSH3, GNF2_GSTM1, GNF2_HPN, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_DN, GOBP_CARBOHYDRATE_PHOSPHORYLATION, WOTTON_RUNX_TARGETS_UP, GOBP_GENERATION_OF_PRECURSOR_METABOLITES_AND_ENERGY, CAIRO_HEPATOBLASTOMA_CLASSES_DN, GOBP_RESPONSE_TO_INSULIN, GOBP_REGULATION_OF_CARBOHYDRATE_METABOLIC_PROCESS, DOANE_RESPONSE_TO_ANDROGEN_DN, GNF2_LCAT, GOBP_CARBOHYDRATE_METABOLIC_PROCESS

GO Biological Process (10): fructose metabolic process (GO:0006000), response to sucrose (GO:0009744), response to glucose (GO:0009749), response to fructose (GO:0009750), response to zinc ion (GO:0010043), response to insulin (GO:0032868), regulation of glycogen metabolic process (GO:0070873), phosphate-containing compound metabolic process (GO:0006796), small molecule metabolic process (GO:0044281), carbohydrate phosphorylation (GO:0046835)

GO Molecular Function (9): ketohexokinase activity (GO:0004454), ATP binding (GO:0005524), identical protein binding (GO:0042802), protein homodimerization activity (GO:0042803), fructose binding (GO:0070061), nucleotide binding (GO:0000166), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (3): cytoplasm (GO:0005737), cytosol (GO:0005829), extracellular exosome (GO:0070062)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
Diseases of carbohydrate metabolism	1
Fructose metabolism	1
Metabolism of carbohydrates and carbohydrate derivatives	1
Diseases of metabolism	1
Disease	1
Metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
response to hexose	2
metabolic process	2
cellular anatomical structure	2
hexose metabolic process	1
response to disaccharide	1
response to metal ion	1
response to peptide hormone	1
glycogen metabolic process	1
regulation of polysaccharide metabolic process	1
regulation of generation of precursor metabolites and energy	1
carbohydrate metabolic process	1
phosphorylation	1
phosphotransferase activity, alcohol group as acceptor	1
carbohydrate kinase activity	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
protein binding	1
identical protein binding	1
protein dimerization activity	1
monosaccharide binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
transferase activity, transferring phosphorus-containing groups	1
catalytic activity	1
intracellular anatomical structure	1
cytoplasm	1
extracellular vesicle	1

Protein interactions and networks

STRING

920 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KHK	GCK	P35557	843
KHK	GCKR	Q14397	830
KHK	SLC2A5	P22732	792
KHK	MAPRE2	Q15555	771
KHK	MAPRE3	Q9UPY8	769
KHK	APC2	O95996	716
KHK	EMILIN1	Q9Y6C2	715
KHK	MAPRE1	Q15691	713
KHK	TKFC	Q3LXA3	708
KHK	ALDOB	P05062	660
KHK	MLXIPL	Q9NP71	655
KHK	AMPD2	Q01433	623
KHK	AKR1B1	P15121	611
KHK	SLC2A2	P11168	604
KHK	SORD	Q00796	597

IntAct

21 interactions, top by confidence:

A	B	Type	Score
LHX9	KHK	psi-mi:“MI:0915”(physical association)	0.560
KHK	LHX9	psi-mi:“MI:0915”(physical association)	0.560
CUEDC2	TBP	psi-mi:“MI:0914”(association)	0.530
DNAJB14	KHK	psi-mi:“MI:0915”(physical association)	0.400
KHK	GLB1	psi-mi:“MI:0915”(physical association)	0.400
COPS5	FBLL1	psi-mi:“MI:0914”(association)	0.350
SPG21	GAPDHS	psi-mi:“MI:0914”(association)	0.350
CST8	ITIH2	psi-mi:“MI:0914”(association)	0.350
DEDD	KHK	psi-mi:“MI:0915”(physical association)	0.000
	KHK	psi-mi:“MI:0915”(physical association)	0.000
CD2BP2	KHK	psi-mi:“MI:0915”(physical association)	0.000
ILK	KHK	psi-mi:“MI:0915”(physical association)	0.000
SNRPB	KHK	psi-mi:“MI:0915”(physical association)	0.000
KHK	LYZ	psi-mi:“MI:0915”(physical association)	0.000
ARRB1	KHK	psi-mi:“MI:0915”(physical association)	0.000
KHK	LCN1	psi-mi:“MI:0915”(physical association)	0.000
CDK5RAP3	KHK	psi-mi:“MI:0915”(physical association)	0.000
RNPS1	KHK	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (29): LHX9 (Two-hybrid), AGL (Co-fractionation), KHK (Co-fractionation), NPEPL1 (Co-fractionation), SULT1C4 (Co-fractionation), LHX9 (Two-hybrid), GLB1 (Affinity Capture-MS), KHK (Affinity Capture-MS), KHK (Affinity Capture-MS), KHK (Affinity Capture-MS), KHK (Affinity Capture-MS), KHK (Affinity Capture-MS), LCN1 (Affinity Capture-MS), KHK (Affinity Capture-MS), LYZ (Affinity Capture-MS)

ESM2 similar proteins: A0A6N3IN21, A3KCL7, A4IFH5, A7MBC0, A7MBI7, D3ZDK7, D3ZDM7, E1BNQ4, P09367, P10950, P11172, P13439, P17256, P20132, P24298, P25409, P31754, P46597, P50053, P97328, Q02974, Q03426, Q0VCW4, Q1JPD3, Q3B8E3, Q3TY86, Q3ZKN0, Q5BJJ5, Q5E9T8, Q5M7T9, Q5R514, Q5R824, Q5RD71, Q5RFE6, Q6PCB7, Q6SKR2, Q80W22, Q8CHP8, Q8CIM3, Q8HZJ0

Diamond homologs: P50053, P97328, Q02974, Q5RD71

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
KHK	“down-regulates quantity”	beta-D-fructofuranose	“chemical modification”
KHK	“up-regulates quantity”	“beta-D-fructofuranose 1-phosphate(2-)”	“chemical modification”
KHK	“up-regulates activity”	PRPS1	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	52
Likely benign	7
Benign	12

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
12032	NM_006488.3(KHK):c.127G>A (p.Ala43Thr)	Pathogenic

SpliceAI

1603 predictions. Top by Δscore:

Variant	Effect	Δscore
2:27087318:TGGAC:T	donor_gain	1.0000
2:27087335:G:GT	donor_gain	1.0000
2:27094779:T:TA	acceptor_gain	1.0000
2:27094784:C:A	acceptor_gain	1.0000
2:27094930:GACAC:G	donor_gain	1.0000
2:27094935:G:GG	donor_gain	1.0000
2:27096715:A:AG	acceptor_gain	1.0000
2:27096715:ATCCT:A	acceptor_gain	1.0000
2:27096716:T:G	acceptor_gain	1.0000
2:27096719:T:A	acceptor_gain	1.0000
2:27096721:T:TA	acceptor_gain	1.0000
2:27096725:CTA:C	acceptor_loss	1.0000
2:27096727:A:AG	acceptor_gain	1.0000
2:27096727:AG:A	acceptor_gain	1.0000
2:27096728:G:GT	acceptor_gain	1.0000
2:27096728:GG:G	acceptor_gain	1.0000
2:27096728:GGA:G	acceptor_gain	1.0000
2:27096728:GGAGC:G	acceptor_gain	1.0000
2:27096798:TGAGG:T	donor_loss	1.0000
2:27096799:GAGGT:G	donor_loss	1.0000
2:27096800:AGGT:A	donor_loss	1.0000
2:27096801:GGTAA:G	donor_loss	1.0000
2:27096802:G:A	donor_loss	1.0000
2:27096802:G:GG	donor_gain	1.0000
2:27096803:T:G	donor_loss	1.0000
2:27097498:A:AG	acceptor_gain	1.0000
2:27097498:ACCAG:A	acceptor_gain	1.0000
2:27097499:C:G	acceptor_gain	1.0000
2:27097500:CAG:C	acceptor_loss	1.0000
2:27097501:A:AG	acceptor_gain	1.0000

AlphaMissense

1949 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:27096787:T:A	W135R	0.998
2:27096787:T:C	W135R	0.998
2:27099539:A:T	D258V	0.998
2:27087288:G:A	G10E	0.997
2:27092380:C:G	C47W	0.997
2:27099695:G:A	G281E	0.997
2:27087287:G:A	G10R	0.996
2:27087287:G:C	G10R	0.996
2:27087287:G:T	G10W	0.996
2:27087288:G:T	G10V	0.996
2:27099538:G:C	D258H	0.996
2:27099539:A:C	D258A	0.996
2:27099539:A:G	D258G	0.996
2:27099694:G:T	G281W	0.996
2:27092379:G:A	C47Y	0.995
2:27092420:G:C	G61R	0.995
2:27096793:C:G	H137D	0.995
2:27099206:G:T	S192I	0.995
2:27099540:C:A	D258E	0.995
2:27099540:C:G	D258E	0.995
2:27092378:T:C	C47R	0.994
2:27097507:G:C	R141P	0.994
2:27099205:A:C	S192R	0.994
2:27099207:C:A	S192R	0.994
2:27099207:C:G	S192R	0.994
2:27087303:A:C	D15A	0.993
2:27092370:C:A	S44Y	0.993
2:27092370:C:T	S44F	0.993
2:27092374:C:A	N45K	0.993
2:27092374:C:G	N45K	0.993

dbSNP variants (sampled 300 via entrez): RS1000198136 (2:27100311 T>C), RS1000282018 (2:27088919 C>A), RS1000454263 (2:27089582 G>T), RS1000529406 (2:27093894 G>A), RS1000593729 (2:27101010 C>A,T), RS1001105483 (2:27099031 A>G), RS1001191239 (2:27088148 G>A,T), RS1001844879 (2:27088557 C>T), RS1002194243 (2:27094716 C>T), RS1002210485 (2:27092339 T>C), RS1002222985 (2:27098922 G>A,C), RS1002468313 (2:27086659 C>T), RS1002527322 (2:27097400 G>A), RS1002542488 (2:27090967 G>A,C), RS1002563565 (2:27098806 TTC>T)

Disease associations

OMIM: gene MIM:614058 | disease phenotypes: MIM:229800

GenCC curated gene-disease

Disease	Classification	Inheritance
essential fructosuria	Moderate	Autosomal recessive

Mondo (1): essential fructosuria (MONDO:0009252)

Orphanet (1): Essential fructosuria (Orphanet:2056)

HPO phenotypes

8 total (8 of 8 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0003074	Hyperglycemia
HP:0010969	Abnormality of glycolipid metabolism
HP:0011033	Impairment of fructose metabolism
HP:0012379	Abnormal circulating enzyme concentration or activity
HP:0030272	Abnormal erythrocyte enzyme concentration or activity
HP:0031979	Abnormal urine carbohydrate level
HP:6000804	Elevated urine fructose level

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST006461_10	Self-reported risk-taking behaviour	1.000000e-07
GCST010697_14	Cortical surface area (min-P)	2.000000e-09
GCST010698_75	Subcortical volume (min-P)	2.000000e-13
GCST010699_41	Brain morphology (min-P)	2.000000e-08
GCST010700_38	Cortical thickness (MOSTest)	3.000000e-08
GCST010701_56	Cortical surface area (MOSTest)	4.000000e-16
GCST010702_20	Subcortical volume (MOSTest)	2.000000e-64
GCST010703_76	Brain morphology (MOSTest)	1.000000e-16

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0008579	risk-taking behaviour
EFO:0004346	neuroimaging measurement
EFO:0004840	cortical thickness

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C538068	Fructosuria (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1275212 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

2 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 28 (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
CHEMBL4549658	PF-06835919	2	19
CHEMBL5441069	LY-3522348	1	9

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — Sugar kinases

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

Ligand	Action	Affinity	Parameter
PF-06835919	Inhibition	8.0	pIC50
LY3522348	Inhibition	7.39	pIC50

Binding affinities (BindingDB)

209 measured of 236 human assays (239 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
2-((1R,5S,6R)-3-(5-cyano-6-((S)- 2-methylazetidine-1-yl)-4- (trifluoromethyl)pyridin-2-yl)-3- azabicyclo[3.1.0]hexan-6-yl)acetic acid	IC50	0.17 nM	US-20250145619: KHK INHIBITOR, PREPARATION METHOD THEREFOR AND USE THEREOF
Preparation of 2-((1R,5S,6R)-3-(5-cyano-6-((S)-2-methylazetidine-1-yl)-4-(trifluoromethyl)pyridin-2-yl)-3-azabicyclo[3.1.0]hexan-6-yl)acetic-2,2-d2 acid and 2-((1R,5S,6R)-3-(5-cyano-6-((S)-2-methylazetidine-1-yl)-4-(trifluoromethyl)pyridin-2-yl-3-d)-3-azabicyclo[3.1.0]hexan-6-yl)acetic-2,2-d2 acid	IC50	0.39 nM	US-20250145619: KHK INHIBITOR, PREPARATION METHOD THEREFOR AND USE THEREOF
Preparation of 2-((1R,5S,6R)-3-(5-cyano-6-((S)-2-methylazetidine-1-yl)-4-(trifluoromethyl)pyridin-2-yl)-3-azabicyclo[3.1.0]hexan-6-yl)acetic-2,2-d2 acid and 2-((1R,5S,6R)-3-(5-cyano-6-((S)-2-methylazetidine-1-yl)-4-(trifluoromethyl)pyridin-2-yl-3-d)-3-azabicyclo[3.1.0]hexan-6-yl)acetic-2,2-d2 acid	IC50	0.44 nM	US-20250145619: KHK INHIBITOR, PREPARATION METHOD THEREFOR AND USE THEREOF
acid	IC50	0.52 nM	US-12331038: Hexone glucokinase inhibitor and use thereof
2-[(1R,5S)-3-[8,8-difluoro-2-(3-fluoro-2-methylazetidin-1-yl)-6,7-dihydro-5H-quinazolin-4-yl]-3-azabicyclo[3.1.0]hexan-6-yl]acetic acid	IC50	0.73 nM	US-12331038: Hexone glucokinase inhibitor and use thereof
acid	IC50	0.82 nM	US-12331038: Hexone glucokinase inhibitor and use thereof
2-[(1S,5R)-3-[7,7-difluoro-2-[(2S)-3-fluoro-2-methylazetidin-1-yl]-5,6-dihydrocyclopenta[d]pyrimidin-4-yl]-3-azabicyclo[3.1.0]hexan-6-yl]acetic acid	IC50	0.9 nM	US-12331038: Hexone glucokinase inhibitor and use thereof
2-[(1S,5R)-3-[5-cyano-6-[(2S,3R)-3-hydroxy-2-methylazetidin-1-yl]-4-(trifluoromethyl)-2-pyridinyl]-3-azabicyclo[3.1.0]hexan-6-yl]acetic acid	IC50	1.5 nM	US-10174007: Substituted 3-azabicyclo[3.1.0]hexanes as ketohexokinase inhibitors
2-[(1R,5S)-3-[3-chloro-5-cyano-6-[(2S,3R)-3-hydroxy-2-methylazetidin-1-yl]-4-(trifluoromethyl)-2-pyridinyl]-3-azabicyclo[3.1.0]hexan-6-yl]acetic acid	IC50	1.5 nM	US-10174007: Substituted 3-azabicyclo[3.1.0]hexanes as ketohexokinase inhibitors
2-[(1R,5S)-3-[5-cyano-4-(1,1-difluoroethyl)-3-fluoro-6-[(2S,3R)-3-hydroxy-2-methylazetidin-1-yl]-2-pyridinyl]-3-azabicyclo[3.1.0]hexan-6-yl]acetic acid	IC50	1.5 nM	US-10174007: Substituted 3-azabicyclo[3.1.0]hexanes as ketohexokinase inhibitors
2-[(1S,5R)-3-[2-[(2R)-3,3-difluoro-2-methylazetidin-1-yl]-8,8-difluoro-6,7-dihydro-5H-quinazolin-4-yl]-3-azabicyclo[3.1.0]hexan-6-yl]acetic acid	IC50	1.5 nM	US-12331038: Hexone glucokinase inhibitor and use thereof
2-[(1S,5R)-3-[2-(3,3-difluoro-2-methylazetidin-1-yl)-8,8-difluoro-6,7-dihydro-5H-quinazolin-4-yl]-3-azabicyclo[3.1.0]hexan-6-yl]acetic acid	IC50	2.2 nM	US-12331038: Hexone glucokinase inhibitor and use thereof
2-[(1R,5S)-3-[2-[(2S)-2-methylazetidin-1-yl]-6-(trifluoromethyl)pyrimidin-4-yl]-3-azabicyclo[3.1.0]hexan-6-yl]acetic acid	IC50	7.07 nM	US-12331038: Hexone glucokinase inhibitor and use thereof
2-[(3R)-1-[7,7-difluoro-2-[(2S)-2-methylazetidin-1-yl]-5,6-dihydrocyclopenta[d]pyrimidin-4-yl]pyrrolidin-3-yl]-N-hydroxyacetamide	IC50	7.29 nM	US-20250145619: KHK INHIBITOR, PREPARATION METHOD THEREFOR AND USE THEREOF
2-(1-(7,7-difluoro-2-((S)-2- methylazetidine-1-yl)-6,7-dihydro-5H- cyclopentadiene[d]pyrimidin-4-yl) pyrrolidin-3-yl)acetic acid	IC50	10.4 nM	US-20250145619: KHK INHIBITOR, PREPARATION METHOD THEREFOR AND USE THEREOF
2-[(1S,5R)-3-[5-methyl-2-[(2S)-2-methylazetidin-1-yl]-6-(trifluoromethyl)pyrimidin-4-yl]-3-azabicyclo[3.1.0]hexan-6-yl]acetic acid	IC50	10.5 nM	US-10174007: Substituted 3-azabicyclo[3.1.0]hexanes as ketohexokinase inhibitors
2-[(1S,5R)-3-[2-[(2S,3R)-3-hydroxy-2-methylazetidin-1-yl]-5-methyl-6-(trifluoromethyl)pyrimidin-4-yl]-3-azabicyclo[3.1.0]hexan-6-yl]acetic acid	IC50	11 nM	US-10174007: Substituted 3-azabicyclo[3.1.0]hexanes as ketohexokinase inhibitors
2-[(1R,5S)-3-[5-chloro-6-(difluoromethyl)-2-[(2S)-2-methylazetidin-1-yl]pyrimidin-4-yl]-3-azabicyclo[3.1.0]hexan-6-yl]acetic acid	IC50	11.1 nM	US-10174007: Substituted 3-azabicyclo[3.1.0]hexanes as ketohexokinase inhibitors
(R)-2-((1R,5S,6R)-3-(5-cyano-6- ((S)-2-methylazetidine-1-yl)-4- (trifluoromethyl)pyridin-2-yl)-3- azabicyclo[3.1.0]hexan-6-yl) propionic acid	IC50	12.6 nM	US-20250145619: KHK INHIBITOR, PREPARATION METHOD THEREFOR AND USE THEREOF
3-(1-(5-cyano-6-((S)-2-methylazetidine- 1-yl)-4-(trifluoromethyl) pyridin-2-yl)pyrrolidin-3-yl) propionic acid	IC50	12.6 nM	US-20250145619: KHK INHIBITOR, PREPARATION METHOD THEREFOR AND USE THEREOF
[(3R,4S)-3,4-Dihydroxypyrrolidin-1-yl]-[4-{2-[(2S)-2-methylazetidin-1-yl]-6-(trifluoromethyl)pyrimidin-4-yl}phenyl]methanone	IC50	12.7 nM	US-12479829: 2-[2-methylazetidin-1-yl]-4-phenyl-6-(trifluoromethyl)-pyrimidine compounds
2-[(1R,5S)-3-[2-[(2S,3R)-3-hydroxy-2-methylazetidin-1-yl]-6-(trifluoromethyl)pyrimidin-4-yl]-3-azabicyclo[3.1.0]hexan-6-yl]acetic acid	IC50	13.7 nM	US-10174007: Substituted 3-azabicyclo[3.1.0]hexanes as ketohexokinase inhibitors
2-[(1R,5S)-3-[2-[(2S)-2-methylazetidin-1-yl]-6-(trifluoromethyl)pyrimidin-4-yl]-3-azabicyclo[3.1.0]hexan-6-yl]acetic acid	IC50	14.2 nM	US-10174007: Substituted 3-azabicyclo[3.1.0]hexanes as ketohexokinase inhibitors
Preparation of 3-((S)-1-(5-cyano-6-((S)-2-methylazetidine-1-yl)-4-(trifluoromethyl)pyridin-2-yl)pyrrolidin-3-yl)propionic acid and 3-((R)-1-(5-cyano-6-((S)-2-methylazetidine-1-yl)-4-(trifluoromethyl)pyridin-2-yl)pyrrolidin-3-yl)propionic acid	IC50	15.4 nM	US-20250145619: KHK INHIBITOR, PREPARATION METHOD THEREFOR AND USE THEREOF
2-[(1R,5S)-3-[5-[(2S)-2-methylazetidin-1-yl]pyrido[3,4-b]pyrazin-7-yl]-3-azabicyclo[3.1.0]hexan-6-yl]acetic acid	IC50	17.3 nM	US-20250145619: KHK INHIBITOR, PREPARATION METHOD THEREFOR AND USE THEREOF
2-[(1R,5S)-3-[6-(difluoromethyl)-5-methyl-2-[(2S)-2-methylazetidin-1-yl]pyrimidin-4-yl]-3-azabicyclo[3.1.0]hexan-6-yl]acetic acid	IC50	17.8 nM	US-10174007: Substituted 3-azabicyclo[3.1.0]hexanes as ketohexokinase inhibitors
4-{2-[(2S)-2-Methylazetidin-1-yl]-6-(trifluoromethyl)pyrimidin-4-yl}benzoic acid	IC50	21.5 nM	US-12479829: 2-[2-methylazetidin-1-yl]-4-phenyl-6-(trifluoromethyl)-pyrimidine compounds
N-[2-Hydroxy-1,1-bis(hydroxymethyl)ethyl]-4-{2-[(2S)-2-methylazetidin-1-yl]-6-(trifluoromethyl)pyrimidin-4-yl}benzamide	IC50	23.4 nM	US-12479829: 2-[2-methylazetidin-1-yl]-4-phenyl-6-(trifluoromethyl)-pyrimidine compounds
Preparation of (R)-2-((1R,5S,6R)-3-(5-cyano-6-((S)-2-methylazetidine-1-yl)-4-(trifluoromethyl)pyridin-2-yl)-3-azabicyclo[3.1.0]hexan-6-yl)propionic acid and (S)-2-((1R,5S,6R)-3-(5-cyano-6-((S)-2-methylazetidine-1-yl)-4-(trifluoromethyl)pyridin-2-yl)-3-azabicyclo[3.1.0]hexan-6-yl)propionic acid	IC50	24.7 nM	US-20250145619: KHK INHIBITOR, PREPARATION METHOD THEREFOR AND USE THEREOF
(S)-2-(2-(5-cyano-6-(2-methylazetidine- 1-yl)-4-(trifluoromethyl)pyridin-2- yl)-2-azaspiro[3.3]heptan-6-yl) acetic acid	IC50	27 nM	US-20250145619: KHK INHIBITOR, PREPARATION METHOD THEREFOR AND USE THEREOF
2-[5-cyano-6-[(2S)-2-methylazetidin-1-yl]-4-(trifluoromethyl)-2-pyridinyl]-2-azaspiro[3.3]heptane-6-carboxylic acid	IC50	27.9 nM	US-20250145619: KHK INHIBITOR, PREPARATION METHOD THEREFOR AND USE THEREOF
2-[(1R,5S)-3-[2-cyano-5-[(2S)-2-methylazetidin-1-yl]pyrido[3,4-b]pyrazin-7-yl]-3-azabicyclo[3.1.0]hexan-6-yl]acetic acid	IC50	30.2 nM	US-20250145619: KHK INHIBITOR, PREPARATION METHOD THEREFOR AND USE THEREOF
2-[(3R)-1-[7,7-difluoro-2-[(2S)-2-methylazetidin-1-yl]-5,6-dihydrocyclopenta[d]pyrimidin-4-yl]pyrrolidin-3-yl]-N-(2-hydroxyethyl)acetamide	IC50	33.3 nM	US-20250145619: KHK INHIBITOR, PREPARATION METHOD THEREFOR AND USE THEREOF
2-[(1R,5S)-3-[2-[(2S,3R)-3-hydroxy-2-methylazetidin-1-yl]-5-methoxy-6-(trifluoromethyl)pyrimidin-4-yl]-3-azabicyclo[3.1.0]hexan-6-yl]acetic acid	IC50	33.9 nM	US-10174007: Substituted 3-azabicyclo[3.1.0]hexanes as ketohexokinase inhibitors
2-(5-cyano-6-((S)-2-methylazetidine- 1-yl)-4-(trifluoromethyl)pyridin-2-yl)- 2-azaspiro[3.4]octan-6-carboxylic acid	IC50	36 nM	US-20250145619: KHK INHIBITOR, PREPARATION METHOD THEREFOR AND USE THEREOF
(S)-2-(2-(7,7-difluoro-2-(2- methylazetidine-1-yl)-6,7-dihydro-5H- cyclopentadiene[d]pyrimidin-4-yl)-2- azaspiro[3.3]heptan-6-yl)acetic acid	IC50	40 nM	US-20250145619: KHK INHIBITOR, PREPARATION METHOD THEREFOR AND USE THEREOF
(S)-6-(7,7-difluoro-2-(2-methylazetidine- 1-yl)-6,7-dihydro-5H- cyclopentadiene[d]pyrimidin-4-yl)-6- azaspiro[3.4]octan-2-carboxylic acid	IC50	42.9 nM	US-20250145619: KHK INHIBITOR, PREPARATION METHOD THEREFOR AND USE THEREOF
(S)-2-(1-(7,7-difluoro-2-(2-methylazetidine- 1-yl)-6,7-dihydro-5H- cyclopentadiene[d]pyrimidin-4-yl) azetidine-3-yl)acetic acid	IC50	47 nM	US-20250145619: KHK INHIBITOR, PREPARATION METHOD THEREFOR AND USE THEREOF
(S)-2-(1-(7,7-difluoro-2-(2- methylazetidine-1-yl)-6,7-dihydro-5H- cyclopentadiene[d]pyrimidin-4-yl) piperidin-4-yl)acetic acid	IC50	52.8 nM	US-20250145619: KHK INHIBITOR, PREPARATION METHOD THEREFOR AND USE THEREOF
2-[(1S,5R)-3-[5-ethyl-2-[(2S,3R)-3-hydroxy-2-methylazetidin-1-yl]-6-(trifluoromethyl)pyrimidin-4-yl]-3-azabicyclo[3.1.0]hexan-6-yl]acetic acid	IC50	53.8 nM	US-10174007: Substituted 3-azabicyclo[3.1.0]hexanes as ketohexokinase inhibitors
2-(7,7-difluoro-2-((S)-2-methylazetidine- 1-yl)-6,7-dihydro-5H-cyclopentadiene[d] pyrimidin-4-yl)-2-azaspiro[3.4]octan-6- carboxylic acid	IC50	59 nM	US-20250145619: KHK INHIBITOR, PREPARATION METHOD THEREFOR AND USE THEREOF
6-[7,7-difluoro-2-[(2S)-2-methylazetidin-1-yl]-5,6-dihydrocyclopenta[d]pyrimidin-4-yl]spiro[3.3]heptane-2-carboxylic acid	IC50	78.3 nM	US-20250145619: KHK INHIBITOR, PREPARATION METHOD THEREFOR AND USE THEREOF
Preparation of 3-((S)-1-(5-cyano-6-((S)-2-methylazetidine-1-yl)-4-(trifluoromethyl)pyridin-2-yl)pyrrolidin-3-yl)propionic acid and 3-((R)-1-(5-cyano-6-((S)-2-methylazetidine-1-yl)-4-(trifluoromethyl)pyridin-2-yl)pyrrolidin-3-yl)propionic acid	IC50	81.2 nM	US-20250145619: KHK INHIBITOR, PREPARATION METHOD THEREFOR AND USE THEREOF
1-(4-methoxyphenyl)-3-methylsulfanyl-6-(1,2,3,6-tetrahydropyridin-4-yl)indazole	IC50	90 nM	US-8822447: Indazole compounds useful as ketohexokinase inhibitors
Preparation of (R)-2-((1R,5S,6R)-3-(5-cyano-6-((S)-2-methylazetidine-1-yl)-4-(trifluoromethyl)pyridin-2-yl)-3-azabicyclo[3.1.0]hexan-6-yl)propionic acid and (S)-2-((1R,5S,6R)-3-(5-cyano-6-((S)-2-methylazetidine-1-yl)-4-(trifluoromethyl)pyridin-2-yl)-3-azabicyclo[3.1.0]hexan-6-yl)propionic acid	IC50	100 nM	US-20250145619: KHK INHIBITOR, PREPARATION METHOD THEREFOR AND USE THEREOF
2-[5-cyano-6-[(2S,3R)-3-hydroxy-2-methylazetidin-1-yl]-4-(trifluoromethyl)-2-pyridinyl]-2-azaspiro[3.3]heptane-6-carboxylic acid	IC50	110 nM	US-20250145619: KHK INHIBITOR, PREPARATION METHOD THEREFOR AND USE THEREOF
2-[(1R,5S)-3-[5-cyclopropyl-2-[(2S,3R)-3-hydroxy-2-methylazetidin-1-yl]-6-(trifluoromethyl)pyrimidin-4-yl]-3-azabicyclo[3.1.0]hexan-6-yl]acetic acid	IC50	111 nM	US-10174007: Substituted 3-azabicyclo[3.1.0]hexanes as ketohexokinase inhibitors
(S)-7-(5-cyano-6-(2- methylazetidine-1-yl)-4- (trifluoromethyl)pyridin-2-yl)-7- azaspiro[3.5]nonan-2-carboxylic acid	IC50	115 nM	US-20250145619: KHK INHIBITOR, PREPARATION METHOD THEREFOR AND USE THEREOF
2-(7,7-difluoro-2-((2S,3R)-3-hydroxy- 2-methylazetidine-1-yl)-6,7-dihydro- 5H-cyclopentadiene[d]pyrimidin-4- yl)-2-azaspiro[3.3]heptan-6- carboxylic acid	IC50	134 nM	US-20250145619: KHK INHIBITOR, PREPARATION METHOD THEREFOR AND USE THEREOF
2-(5-(7,7-difluoro-2-((S)-2- methylazetidine-1-yl)-6,7-dihydro-5H- cyclopentadiene[c]pyrimidin-4-yl) hexahydropyrrolo[3,4-c]pyrrolo- 2(1H)-yl)acetic acid	IC50	142 nM	US-20250145619: KHK INHIBITOR, PREPARATION METHOD THEREFOR AND USE THEREOF

ChEMBL bioactivities

963 potent at pChembl≥5 of 1016 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.30	IC50	0.5	nM	CHEMBL5402865
9.22	IC50	0.6	nM	CHEMBL5611924
9.00	IC50	1	nM	CHEMBL4754053
8.93	IC50	1.17	nM	CHEMBL5749120
8.89	IC50	1.3	nM	CHEMBL5613941
8.82	IC50	1.5	nM	CHEMBL5613460
8.82	IC50	1.5	nM	CHEMBL4754053
8.82	IC50	1.5	nM	CHEMBL5945293
8.82	IC50	1.5	nM	CHEMBL5844297
8.82	IC50	1.5	nM	CHEMBL5927921
8.82	IC50	1.5	nM	CHEMBL5900755
8.82	IC50	1.5	nM	CHEMBL5826271
8.80	IC50	1.6	nM	CHEMBL5614311
8.80	IC50	1.59	nM	CHEMBL5848521
8.70	IC50	2	nM	CHEMBL2063924
8.70	IC50	2	nM	CHEMBL5393859
8.70	IC50	2	nM	CHEMBL5613013
8.64	IC50	2.3	nM	CHEMBL5612048
8.62	IC50	2.4	nM	CHEMBL5777265
8.62	IC50	2.4	nM	CHEMBL5947241
8.59	IC50	2.6	nM	CHEMBL5844297
8.59	IC50	2.6	nM	CHEMBL5927921
8.59	IC50	2.6	nM	CHEMBL5900755
8.59	IC50	2.6	nM	CHEMBL5826271
8.58	IC50	2.63	nM	CHEMBL5848521
8.52	IC50	3	nM	CHEMBL5410032
8.49	IC50	3.2	nM	CHEMBL6174745
8.48	IC50	3.3	nM	CHEMBL4754053
8.48	IC50	3.3	nM	CHEMBL5748349
8.48	IC50	3.3	nM	CHEMBL5794443
8.45	IC50	3.58	nM	CHEMBL5983719
8.44	IC50	3.6	nM	CHEMBL5945293
8.44	IC50	3.65	nM	CHEMBL5432883
8.44	IC50	3.63	nM	CHEMBL5394335
8.43	IC50	3.7	nM	CHEMBL5847184
8.43	IC50	3.7	nM	CHEMBL5792962
8.43	IC50	3.71	nM	CHEMBL5410032
8.41	IC50	3.87	nM	CHEMBL5432883
8.40	IC50	4	nM	CHEMBL5410032
8.40	IC50	4	nM	CHEMBL5432883
8.40	IC50	4	nM	CHEMBL5394335
8.40	IC50	4	nM	CHEMBL5397861
8.40	IC50	3.98	nM	CHEMBL5819082
8.38	IC50	4.2	nM	CHEMBL6170657
8.36	IC50	4.4	nM	CHEMBL5844297
8.36	IC50	4.4	nM	CHEMBL5927921
8.36	IC50	4.4	nM	CHEMBL5900755
8.36	IC50	4.4	nM	CHEMBL5826271
8.34	Ki	4.53	nM	PF-06835919
8.33	IC50	4.63	nM	CHEMBL6057719

PubChem BioAssay actives

225 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-[4-[7,7-difluoro-2-[(2R)-2-(trifluoromethyl)azetidin-1-yl]-5,6-dihydrocyclopenta[d]pyrimidin-4-yl]phenyl]oxetan-3-amine	2014108: Inhibition of KHK (unknown origin)	ic50	0.0005	uM
3-[3-[[6-[(3aR,6aS)-2,3,3a,4,6,6a-hexahydro-1H-pyrrolo[3,4-c]pyrrol-5-yl]-3-cyano-4-(trifluoromethyl)-2-pyridinyl]amino]-4-methylsulfanylphenyl]propanoic acid	2126503: Inhibition of recombinant His tagged human KHK-C incubated for 60 mins in presence of ATP by ADP-GloTM kinase assay	ic50	0.0006	uM
2-[(1S,5R)-3-[5-cyano-6-[(2S,3R)-3-hydroxy-2-methylazetidin-1-yl]-4-(trifluoromethyl)-2-pyridinyl]-3-azabicyclo[3.1.0]hexan-6-yl]acetic acid	1681404: Inhibition of 1 nM recombinant human N-terminal His-tagged KHKC expressed in Escherichia coli BL21 (DE3) using fructose as substrate preincubated for 30 mins followed by ATP addition and measured for 3 hrs by pyruvate kinase-lactate dehydrogenase coupled assay	ic50	0.0010	uM
6-[(3aR,6aS)-2,3,3a,4,6,6a-hexahydro-1H-pyrrolo[3,4-c]pyrrol-5-yl]-2-(5-chloro-2-methylsulfanylanilino)-4-(trifluoromethyl)pyridine-3-carbonitrile	2126503: Inhibition of recombinant His tagged human KHK-C incubated for 60 mins in presence of ATP by ADP-GloTM kinase assay	ic50	0.0013	uM
6-[(3aR,6aS)-2,3,3a,4,6,6a-hexahydro-1H-pyrrolo[3,4-c]pyrrol-5-yl]-2-[5-(hydroxymethyl)-2-methylsulfanylanilino]-4-(trifluoromethyl)pyridine-3-carbonitrile	2126503: Inhibition of recombinant His tagged human KHK-C incubated for 60 mins in presence of ATP by ADP-GloTM kinase assay	ic50	0.0015	uM
6-[(3aS,6aR)-2,3,3a,4,6,6a-hexahydro-1H-pyrrolo[3,4-c]pyrrol-5-yl]-2-[2-(difluoromethylsulfanyl)anilino]-4-(trifluoromethyl)pyridine-3-carbonitrile	2126503: Inhibition of recombinant His tagged human KHK-C incubated for 60 mins in presence of ATP by ADP-GloTM kinase assay	ic50	0.0016	uM
6-[1-(azetidin-3-yl)pyrazol-4-yl]-2-[(2S)-2-methylazetidin-1-yl]-4-(trifluoromethyl)pyridine-3-carbonitrile	2023150: Inhibition of KHK in human HepG2 cells incubated for 3 hrs by Rapidfire MS analysis	ic50	0.0020	uM
3-[3-[[6-[(3aR,6aS)-2,3,3a,4,6,6a-hexahydro-1H-pyrrolo[3,4-c]pyrrol-5-yl]-3-cyano-4-(trifluoromethyl)-2-pyridinyl]amino]-4-methylsulfanylphenyl]propanamide	2126503: Inhibition of recombinant His tagged human KHK-C incubated for 60 mins in presence of ATP by ADP-GloTM kinase assay	ic50	0.0020	uM
8-N-(cyclopropylmethyl)-2-(2,6-diazaspiro[3.4]octan-6-yl)-4-N-(2-methylsulfanylphenyl)pyrimido[5,4-d]pyrimidine-4,8-diamine	674601: Inhibition of recombinant human hepatic KHKC	ic50	0.0020	uM
[3-[[6-[(3aS,6aR)-2,3,3a,4,6,6a-hexahydro-1H-pyrrolo[3,4-c]pyrrol-5-yl]-3-cyano-4-(trifluoromethyl)-2-pyridinyl]amino]-4-methylsulfanylphenyl]methoxy-methylphosphinic acid	2126503: Inhibition of recombinant His tagged human KHK-C incubated for 60 mins in presence of ATP by ADP-GloTM kinase assay	ic50	0.0023	uM
2-[(2S)-2-methylazetidin-1-yl]-4-[1-(1-methylazetidin-3-yl)pyrazol-4-yl]-6-(trifluoromethyl)pyrimidine	2023150: Inhibition of KHK in human HepG2 cells incubated for 3 hrs by Rapidfire MS analysis	ic50	0.0030	uM
4-[1-(azetidin-3-yl)pyrazol-4-yl]-2-[(2S)-2-methylazetidin-1-yl]-6-(trifluoromethyl)pyrimidine	2023149: Inhibition of human KHK-A preincubated for 15 mins followed by substrate addition and measured after 20 mins in presence of ATP by Rapidfire MS analysis	ic50	0.0040	uM
2-[(2S)-2-methylazetidin-1-yl]-6-(1-piperidin-4-ylpyrazol-4-yl)-4-(trifluoromethyl)pyridine-3-carbonitrile	2023148: Inhibition of human KHK-C preincubated for 15 mins followed by substrate addition and measured after 20 mins in presence of ATP by Rapidfire MS analysis	ic50	0.0040	uM
6-[1-(1-ethylpiperidin-4-yl)pyrazol-4-yl]-2-[(2S)-2-methylazetidin-1-yl]-4-(trifluoromethyl)pyridine-3-carbonitrile	2023149: Inhibition of human KHK-A preincubated for 15 mins followed by substrate addition and measured after 20 mins in presence of ATP by Rapidfire MS analysis	ic50	0.0040	uM
2-[(1R,5S)-3-[2-[(2S)-2-methylazetidin-1-yl]-6-(trifluoromethyl)pyrimidin-4-yl]-3-azabicyclo[3.1.0]hexan-6-yl]acetic acid	1681429: Mixed noncompetitive inhibition of recombinant human N-terminal His-tagged KHKC expressed in Escherichia coli BL21 (DE3) using fructose as substrate preincubated for 30 mins followed by ATP addition and measured for 30 mins by Lineweaver-burk plot analysis	ki	0.0045	uM
6-[1-(2-hydroxyethyl)pyrazol-4-yl]-2-[(2S)-2-methylazetidin-1-yl]-4-(trifluoromethyl)pyridine-3-carbonitrile	2023149: Inhibition of human KHK-A preincubated for 15 mins followed by substrate addition and measured after 20 mins in presence of ATP by Rapidfire MS analysis	ic50	0.0050	uM
6-[1-[1-(2-aminoacetyl)piperidin-4-yl]pyrazol-4-yl]-2-[(2S)-2-methylazetidin-1-yl]-4-(trifluoromethyl)pyridine-3-carbonitrile	2023148: Inhibition of human KHK-C preincubated for 15 mins followed by substrate addition and measured after 20 mins in presence of ATP by Rapidfire MS analysis	ic50	0.0060	uM
2-[(2S)-2-methylazetidin-1-yl]-6-[1-[2-(4-methylpiperazin-1-yl)-2-oxoethyl]pyrazol-4-yl]-4-(trifluoromethyl)pyridine-3-carbonitrile	2023148: Inhibition of human KHK-C preincubated for 15 mins followed by substrate addition and measured after 20 mins in presence of ATP by Rapidfire MS analysis	ic50	0.0060	uM
2-[(2S)-2-methylazetidin-1-yl]-6-[1-(1-methylpiperidin-4-yl)pyrazol-4-yl]-4-(trifluoromethyl)pyridine-3-carbonitrile	2023148: Inhibition of human KHK-C preincubated for 15 mins followed by substrate addition and measured after 20 mins in presence of ATP by Rapidfire MS analysis	ic50	0.0060	uM
6-[1-[2-[(3S,4S)-3,4-dihydroxypyrrolidin-1-yl]-2-oxoethyl]pyrazol-4-yl]-2-[(2S)-2-methylazetidin-1-yl]-4-(trifluoromethyl)pyridine-3-carbonitrile	2023149: Inhibition of human KHK-A preincubated for 15 mins followed by substrate addition and measured after 20 mins in presence of ATP by Rapidfire MS analysis	ic50	0.0070	uM
8-N-(2-methoxyethyl)-4-N-(2-methylsulfanylphenyl)-2-piperazin-1-ylpyrimido[5,4-d]pyrimidine-4,8-diamine	656473: Inhibition of human ketohexokinase isoform C expressed in Escherichia coli BL21 (DE3) cells using D-fructose as substrate after 12 to 15 mins by fluorescence polarization assay	ic50	0.0070	uM
4-N-(2-methylsulfanylphenyl)-2-piperazin-1-ylpyrimido[5,4-d]pyrimidine-4,8-diamine	656473: Inhibition of human ketohexokinase isoform C expressed in Escherichia coli BL21 (DE3) cells using D-fructose as substrate after 12 to 15 mins by fluorescence polarization assay	ic50	0.0071	uM
2-[(2S)-2-methylazetidin-1-yl]-4-(1-piperidin-4-ylpyrazol-4-yl)-6-(trifluoromethyl)pyrimidine	2023149: Inhibition of human KHK-A preincubated for 15 mins followed by substrate addition and measured after 20 mins in presence of ATP by Rapidfire MS analysis	ic50	0.0080	uM
8-N-(cyclopropylmethyl)-2-(2,6-diazaspiro[3.3]heptan-2-yl)-4-N-(2-methylsulfanylphenyl)pyrimido[5,4-d]pyrimidine-4,8-diamine	656473: Inhibition of human ketohexokinase isoform C expressed in Escherichia coli BL21 (DE3) cells using D-fructose as substrate after 12 to 15 mins by fluorescence polarization assay	ic50	0.0080	uM
4-N-(2-methylsulfanylphenyl)-2-piperazin-1-yl-8-N-(pyridin-2-ylmethyl)pyrimido[5,4-d]pyrimidine-4,8-diamine	656473: Inhibition of human ketohexokinase isoform C expressed in Escherichia coli BL21 (DE3) cells using D-fructose as substrate after 12 to 15 mins by fluorescence polarization assay	ic50	0.0098	uM
2-[4-(aminomethyl)piperidin-1-yl]-8-N-(cyclopropylmethyl)-4-N-(2-methylsulfanylphenyl)pyrimido[5,4-d]pyrimidine-4,8-diamine	656473: Inhibition of human ketohexokinase isoform C expressed in Escherichia coli BL21 (DE3) cells using D-fructose as substrate after 12 to 15 mins by fluorescence polarization assay	ic50	0.0100	uM
8-N-(cyclopropylmethyl)-4-N-(2-methylsulfanylphenyl)-2-piperazin-1-ylpyrimido[5,4-d]pyrimidine-4,8-diamine	1451638: Inhibition of KHK (unknown origin) using D-fructose as substrate after 60 mins in presence of ATP by LC-MS analysis	ic50	0.0120	uM
2-[(1R,5S)-3-[2-[(2S,3R)-3-hydroxy-2-methylazetidin-1-yl]-6-(trifluoromethyl)pyrimidin-4-yl]-3-azabicyclo[3.1.0]hexan-6-yl]acetic acid	1681404: Inhibition of 1 nM recombinant human N-terminal His-tagged KHKC expressed in Escherichia coli BL21 (DE3) using fructose as substrate preincubated for 30 mins followed by ATP addition and measured for 3 hrs by pyruvate kinase-lactate dehydrogenase coupled assay	ic50	0.0140	uM
2-[(2S)-2-methylazetidin-1-yl]-6-(1H-pyrazol-4-yl)-4-(trifluoromethyl)pyridine-3-carbonitrile	2023148: Inhibition of human KHK-C preincubated for 15 mins followed by substrate addition and measured after 20 mins in presence of ATP by Rapidfire MS analysis	ic50	0.0140	uM
8-N-(cyclopropylmethyl)-2-(3,9-diazaspiro[5.5]undecan-3-yl)-4-N-(2-methylsulfanylphenyl)pyrimido[5,4-d]pyrimidine-4,8-diamine	674601: Inhibition of recombinant human hepatic KHKC	ic50	0.0150	uM
4-N-(2-methylsulfanylphenyl)-2-piperazin-1-yl-8-N-(1,3-thiazol-2-ylmethyl)pyrimido[5,4-d]pyrimidine-4,8-diamine	656473: Inhibition of human ketohexokinase isoform C expressed in Escherichia coli BL21 (DE3) cells using D-fructose as substrate after 12 to 15 mins by fluorescence polarization assay	ic50	0.0160	uM
8-N-(cyclobutylmethyl)-4-N-(2-methylsulfanylphenyl)-2-piperazin-1-ylpyrimido[5,4-d]pyrimidine-4,8-diamine	656473: Inhibition of human ketohexokinase isoform C expressed in Escherichia coli BL21 (DE3) cells using D-fructose as substrate after 12 to 15 mins by fluorescence polarization assay	ic50	0.0180	uM
2-[(3R)-3-aminopiperidin-1-yl]-8-N-(cyclopropylmethyl)-4-N-(2-methylsulfanylphenyl)pyrimido[5,4-d]pyrimidine-4,8-diamine	656473: Inhibition of human ketohexokinase isoform C expressed in Escherichia coli BL21 (DE3) cells using D-fructose as substrate after 12 to 15 mins by fluorescence polarization assay	ic50	0.0180	uM
2-[4-[2-[(2S)-2-methylazetidin-1-yl]-6-(trifluoromethyl)pyrimidin-4-yl]pyrazol-1-yl]-1-piperazin-1-ylethanone	2023148: Inhibition of human KHK-C preincubated for 15 mins followed by substrate addition and measured after 20 mins in presence of ATP by Rapidfire MS analysis	ic50	0.0200	uM
(3aS,4S,6aS)-2-[5-cyano-6-[(2S)-2-methylazetidin-1-yl]-4-(trifluoromethyl)-2-pyridinyl]-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrole-4-carboxylic acid	2016285: Inhibition of N-terminal his tagged human recombinant KHK-C expressed in Escherichia coli incubated for 60 mins in presence of ATP by ADP Glo assay	ic50	0.0219	uM
6-[1-[2-(dimethylamino)ethyl]pyrazol-4-yl]-2-[(2S)-2-methylazetidin-1-yl]-4-(trifluoromethyl)pyridine-3-carbonitrile	2023149: Inhibition of human KHK-A preincubated for 15 mins followed by substrate addition and measured after 20 mins in presence of ATP by Rapidfire MS analysis	ic50	0.0220	uM
1-(4-fluorophenyl)-3-methylsulfanyl-6-(1,2,3,6-tetrahydropyridin-4-yl)indazole	609452: Inhibition of KHK-mediated conversion of D-fructose to fructose-1-phosphate after 60 mins by high throughput mass spectrometry analysis	ic50	0.0230	uM
2-[(3S)-3-aminopiperidin-1-yl]-8-N-(cyclopropylmethyl)-4-N-(2-methylsulfanylphenyl)pyrimido[5,4-d]pyrimidine-4,8-diamine	656473: Inhibition of human ketohexokinase isoform C expressed in Escherichia coli BL21 (DE3) cells using D-fructose as substrate after 12 to 15 mins by fluorescence polarization assay	ic50	0.0230	uM
3-[(3S)-1-[7,7-difluoro-2-[(2R)-2-(trifluoromethyl)azetidin-1-yl]-5,6-dihydrocyclopenta[d]pyrimidin-4-yl]pyrrolidin-3-yl]propanoic acid	2016285: Inhibition of N-terminal his tagged human recombinant KHK-C expressed in Escherichia coli incubated for 60 mins in presence of ATP by ADP Glo assay	ic50	0.0259	uM
8-N-(cyclopropylmethyl)-4-N-(2-methylsulfanylphenyl)-2-(4-piperazin-1-ylpiperidin-1-yl)pyrimido[5,4-d]pyrimidine-4,8-diamine	674601: Inhibition of recombinant human hepatic KHKC	ic50	0.0280	uM
6-[1-(1-acetylpiperidin-4-yl)pyrazol-4-yl]-2-[(2S)-2-methylazetidin-1-yl]-4-(trifluoromethyl)pyridine-3-carbonitrile	2023149: Inhibition of human KHK-A preincubated for 15 mins followed by substrate addition and measured after 20 mins in presence of ATP by Rapidfire MS analysis	ic50	0.0290	uM
8-N-(cyclopropylmethyl)-2-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]-4-N-(2-methylsulfanylphenyl)pyrimido[5,4-d]pyrimidine-4,8-diamine	674601: Inhibition of recombinant human hepatic KHKC	ic50	0.0300	uM
4-N-(2-methylsulfanylphenyl)-2-piperazin-1-yl-8-N-(thiophen-2-ylmethyl)pyrimido[5,4-d]pyrimidine-4,8-diamine	656473: Inhibition of human ketohexokinase isoform C expressed in Escherichia coli BL21 (DE3) cells using D-fructose as substrate after 12 to 15 mins by fluorescence polarization assay	ic50	0.0300	uM
2-[3-(aminomethyl)azetidin-1-yl]-8-N-(cyclopropylmethyl)-4-N-(2-methylsulfanylphenyl)pyrimido[5,4-d]pyrimidine-4,8-diamine	656473: Inhibition of human ketohexokinase isoform C expressed in Escherichia coli BL21 (DE3) cells using D-fructose as substrate after 12 to 15 mins by fluorescence polarization assay	ic50	0.0300	uM
2-[(2S)-2-methylazetidin-1-yl]-6-[1-(oxan-4-yl)pyrazol-4-yl]-4-(trifluoromethyl)pyridine-3-carbonitrile	2023149: Inhibition of human KHK-A preincubated for 15 mins followed by substrate addition and measured after 20 mins in presence of ATP by Rapidfire MS analysis	ic50	0.0330	uM
6-[1-[2-[(3R,4R)-3,4-dihydroxypyrrolidin-1-yl]-2-oxoethyl]pyrazol-4-yl]-2-[(2S)-2-methylazetidin-1-yl]-4-(trifluoromethyl)pyridine-3-carbonitrile	2023149: Inhibition of human KHK-A preincubated for 15 mins followed by substrate addition and measured after 20 mins in presence of ATP by Rapidfire MS analysis	ic50	0.0340	uM
1-(3-methylphenyl)-3-methylsulfanyl-6-(1,2,3,6-tetrahydropyridin-4-yl)indazole	609452: Inhibition of KHK-mediated conversion of D-fructose to fructose-1-phosphate after 60 mins by high throughput mass spectrometry analysis	ic50	0.0340	uM
(3aS,4S,6aS)-2-[7,7-difluoro-2-[(2S)-2-methylazetidin-1-yl]-5,6-dihydrocyclopenta[d]pyrimidin-4-yl]-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrole-4-carboxylic acid	2016285: Inhibition of N-terminal his tagged human recombinant KHK-C expressed in Escherichia coli incubated for 60 mins in presence of ATP by ADP Glo assay	ic50	0.0347	uM
3-[(3S)-1-[7,7-difluoro-2-[(2S)-2-methylazetidin-1-yl]-5,6-dihydrocyclopenta[d]pyrimidin-4-yl]pyrrolidin-3-yl]propanoic acid	2016285: Inhibition of N-terminal his tagged human recombinant KHK-C expressed in Escherichia coli incubated for 60 mins in presence of ATP by ADP Glo assay	ic50	0.0351	uM
2-[4-[5-cyano-6-[(2S)-2-methylazetidin-1-yl]-4-(trifluoromethyl)-2-pyridinyl]pyrazol-1-yl]-N-(2-hydroxyethyl)acetamide	2023149: Inhibition of human KHK-A preincubated for 15 mins followed by substrate addition and measured after 20 mins in presence of ATP by Rapidfire MS analysis	ic50	0.0380	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression	5
Aflatoxin B1	increases methylation, affects expression, decreases expression	5
sodium arsenite	decreases expression, increases expression	3
bisphenol A	affects expression, increases expression	2
Acetaminophen	decreases expression	2
Estradiol	decreases expression, affects cotreatment	2
Cyclosporine	decreases expression	2
aristolochic acid I	decreases expression	1
lasiocarpine	decreases expression	1
methyleugenol	decreases expression	1
chlortoluron	decreases expression	1
lead acetate	decreases expression	1
afimoxifene	decreases response to substance	1
enilconazole	decreases expression	1
butyraldehyde	increases expression	1
benzo(k)fluoranthene	decreases expression	1
zinc chromate	decreases expression, increases abundance	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
4-aminophenylarsenoxide	affects binding, decreases reaction	1
S-(1,2-dichlorovinyl)cysteine	decreases expression, decreases reaction	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
chromium hexavalent ion	decreases expression, increases abundance	1
cyproconazole	decreases expression	1
perfluoro-n-nonanoic acid	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
jinfukang	affects cotreatment, increases expression	1
Sunitinib	decreases expression	1
Arsenic Trioxide	affects binding, decreases reaction	1

ChEMBL screening assays

57 unique, capped per target: 57 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1273541	Binding	Inhibition of ketohexokinase assessed as conversion of D-fructose to fructose-1-phosphate after 60 mins	Electron density guided fragment-based lead discovery of ketohexokinase inhibitors. — J Med Chem

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B2ZQ	Abcam HEK293T KHK KO	Transformed cell line	Female

Clinical trials (associated diseases)

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