Therapeutic Target Details
| Target ID: | T32 |
| Target Name: | Ketohexokinase |
| Synonyms: | KHK |
| GENE: | KHK |
| Action: | inhibitor |
| Class: | Enzyme |
| UniProtKB ID: | P50053 |
| Entry Name: | KHK_HUMAN |
| Related Drugs: | PF-06835919 |
| Mechanism: | Ketohexokinase is an enzyme that catalyses the phosphorylation of fructose to fructose-1-phosphate, an important step in fructose metabolism. Fructose overconsumption leads to elevated ketohexokinase expression, impaired fatty acid oxidation, increased DNL, hepatic steatosis and impaired insulin signalling, but this effect can be mitigated by the liver-specific deletion of ketohexokinase in high fructose-fed mice. |
| Reference (PMIDs): | 32694791; 32502381 |
| Candidate ID | Source ID | Source Type | Compound Type | Candidate Name | Inclusion Criteria |
|---|
| Compound ID | Source ID | Source Type | Compound Name | Molecular Weight | Molecular Formula | Molecular Species | |
|---|---|---|---|---|---|---|---|
| B002173 | CHEMBL1236391 | Small molecule | -- | 366.49 | C20H22N4OS | BASE | Details |
| B045999 | CHEMBL1463512 | Small molecule | -- | 214.15 | C9H5F3N2O | NEUTRAL | Details |
| B055893 | CHEMBL1500542 | Small molecule | -- | 217.27 | C12H15N3O | NEUTRAL | Details |
| B096083 | CHEMBL1809150 | Small molecule | -- | 323.47 | C19H21N3S | BASE | Details |
| B096084 | CHEMBL1809151 | Small molecule | -- | 324.45 | C18H20N4S | BASE | Details |
| B096085 | CHEMBL1809152 | Small molecule | -- | 321.45 | C19H19N3S | BASE | Details |
| B096086 | CHEMBL1809153 | Small molecule | -- | 317.42 | C19H15N3S | NEUTRAL | Details |
| B096087 | CHEMBL1809154 | Small molecule | -- | 336.46 | C19H20N4S | BASE | Details |
| B096088 | CHEMBL1809155 | Small molecule | -- | 339.46 | C19H21N3OS | BASE | Details |
| B096089 | CHEMBL1809156 | Small molecule | -- | 353.49 | C20H23N3OS | BASE | Details |
| Article ID | PMID | Source | Title | |
|---|---|---|---|---|
| A02345 | 34409309 | STAR Protoc | A luminescence-based protocol for assessing fructose metabolism via quantification of ketohexokinase enzymatic activity in mouse or human hepatocytes. | Details |
| A02927 | 34195217 | Front Nutr | Grape Polyphenols Attenuate Diet-Induced Obesity and Hepatic Steatosis in Mice in Association With Reduced Butyrate and Increased Markers of Intestinal Carbohydrate Oxidation. | Details |
| A04317 | 33667726 | Mol Metab | Pharmacologic inhibition of ketohexokinase prevents fructose-induced metabolic dysfunction. | Details |
| A04831 | 33490936 | JHEP Rep | Ketohexokinase inhibition improves NASH by reducing fructose-induced steatosis and fibrogenesis. | Details |
| A05527 | 33218081 | Biology (Basel) | Organismal Fructose Metabolism in Health and Non-Alcoholic Fatty Liver Disease. | Details |
| A05972 | 33057854 | Curr Diab Rep | Tissue-Specific Fructose Metabolism in Obesity and Diabetes. | Details |
| A06369 | 32910646 | J Med Chem | Discovery of PF-06835919: A Potent Inhibitor of Ketohexokinase (KHK) for the Treatment of Metabolic Disorders Driven by the Overconsumption of Fructose. | Details |
| A06932 | 32694791 | Nat Metab | The small intestine shields the liver from fructose-induced steatosis. | Details |
| A07203 | 32583961 | Clin Transl Sci | Evolving Role for Pharmacotherapy in NAFLD/NASH. | Details |
| A07966 | 32296880 | J Mol Med (Berl) | HIF-P4H-2 inhibition enhances intestinal fructose metabolism and induces thermogenesis protecting against NAFLD. | Details |
| A08928 | 31935149 | Crit Rev Clin Lab Sci | Fructose and hepatic insulin resistance. | Details |
| A09516 | 31713637 | Cell Mol Life Sci | Recent advances in the pathogenesis of hereditary fructose intolerance: implications for its treatment and the understanding of fructose-induced non-alcoholic fatty liver disease. | Details |
| A11662 | 30798914 | Med Hypotheses | Fructose-associated hepatotoxicity indexed by the lactate dehydrogenase isoenzyme LDH-5. | Details |
| A15307 | 28972537 | J Clin Invest | Divergent effects of glucose and fructose on hepatic lipogenesis and insulin signaling. | Details |
| A17041 | 28034722 | Brain Res | Specific regions of the brain are capable of fructose metabolism. | Details |
| A19922 | 26264689 | Proc Nutr Soc | Dietary carbohydrate and control of hepatic gene expression: mechanistic links from ATP and phosphate ester homeostasis to the carbohydrate-response element-binding protein. | Details |
| A25056 | 33907358 | J Proteomics Bioinform | High Fat Diet-Induced Changes in Hepatic Protein Abundance in Mice. | Details |
| A49355 | 35779864 | Drug Metab Dispos | Transporter-Enzyme Interplay in the Pharmacokinetics of PF-06835919, A First-in-class Ketohexokinase Inhibitor for Metabolic Disorders and Non-alcoholic Fatty Liver Disease. | Details |
| A49931 | 35590219 | Med (N Y) | Inhibition of ketohexokinase in adults with NAFLD reduces liver fat and inflammatory markers: A randomized phase 2 trial. | Details |
| A51762 | 34302121 | Int J Obes (Lond) | Non-hematopoietic IL-4Rα expression contributes to fructose-driven obesity and metabolic sequelae. | Details |