Hexokinase (ScHEX1), a glycolytic enzyme, is inhibited by n-acetylglucosamine, which causes it to detach from the mitochondrial outer membrane. This detachment activates the NLRP3 inflammasome [1].

Benitrobenrazide (Hexokinase 2 inhibitor 1) is a hexokinase 2 inhibitor with anticancer and antitumor activity.Benitrobenrazide inhibits the growth of tumors and can be used in cancer research.

3-Bromopyruvic acid (Hexokinase II Inhibitor II, 3-BP) is a hexokinase II inhibitor with Ki of 2.4 mM for glycolysis/hexokinase inhibition. It is inhibitor of tumour cell energy metabolism and chemopotentiator of platinum drugs.

In cells, D-Glucose 6-phosphate potassium salt (G6P) is generated when glucose is phosphorylated by hexokinase or glucokinase or by the conversion of glucose-1-phosphate by phosphoglucomutase during glycogenolysis. G6P lies at the beginning of both glycolysis and the pentose phosphate pathways. It also can be stored as glycogen when blood glucose levels are high.

MK-0941 free base is an orally active glucokinase activator, exhibiting strong glucose-lowering activity and is a potential therapeutic agent for treatment of type 2 diabetes.

Globalagliatin (LY2608204) has been used in trials studying the treatment of Diabetes Mellitus, Type 2.

PF-04937319 is an activator of glucokinase (EC50 =154.4  μM). PF-04937319 maintains glucose-lowering efficacy while mitigating the risk of hypoglycemia observed with many other glucokinase activators. PF-04937319 can be used in research on the treatment of type 2 diabetes mellitus.

Ketohexokinase inhibitor 1 is a ketohexokinase inhibitor (IC50s: 8.4 nM and 66 nM for KHK-C and KHK-A, respectively).

2-Deoxy-D-glucose (2-DG) is an analog of glucose, an inhibitor of glycolysis. 2-Deoxy-D-glucose has antiviral activity, as well as inhibitory cell proliferation and apoptosis-inducing activity.

2-deoxy-D-Glucose-13C6is intended for use as an internal standard for the quantification of 2-deoxy-D-glucose by GC- or LC-MS. 2-deoxy-D-Glucose is a glucose antimetabolite and an inhibitor of glycolysis.1,2It inhibits hexokinase, the enzyme that converts glucose to glucose-6-phosphate, as well as phosphoglucose isomerase, the enzyme that converts glucose-6-phosphate to fructose-6-phosphate.32-deoxy-D-Glucose (16 mM) induces apoptosis in SK-BR-3 cells, as well as inhibits the growth of 143B osteosarcoma cells cultured under hypoxic conditions when used at a concentration of 2 mg/ml.4,5In vivo, 2-deoxy-D-glucose (500 mg/kg) reduces tumor growth in 143B osteosarcoma and MV522 non-small cell lung cancer mouse xenograft models when used alone or in combination with doxorubicin or paclitaxel .6 1.Kang, H.T., and Hwang, E.S.2-Deoxyglucose: An anticancer and antiviral therapeutic, but not any more a low glucose mimeticLife Sci.78(12)1392-1399(2006) 2.Aft, R.L., Zhang, F.W., and Gius, D.Evaluation of 2-deoxy-D-glucose as a chemotherapeutic agent: Mechanism of cell deathBr. J. Cancer87(7)805-812(2002) 3.Ralser, M., Wamelink, M.M., Struys, E.A., et al.A catabolic block does not sufficiently explain how 2-deoxy-D-glucose inhibits cell growthProc. Natl. Acad. Sci. USA105(46)17807-17811(2008) 4.Liu, H., Savaraj, N., Priebe, W., et al.Hypoxia increases tumor cell sensitivity to glycolytic inhibitors: A strategy for solid tumor therapy (Model C)Biochem. Pharmacol.64(12)1745-1751(2002) 5.Zhang, X.D., Deslandes, E., Villedieu, M., et al.Effect of 2-deoxy-D-glucose on various malignant cell lines in vitroAnticancer Res.26(5A)3561-3566(2006) 6.Maschek, G., Savaraj, N., Priebe, W., et al.2-deoxy-D-glucose increases the efficacy of adriamycin and paclitaxel in human osteosarcoma and non-small cell lung cancers in vivoCancer Res.64(1)31-34(2004)

AMG-3969 is an effective glucokinase-glucokinase regulatory protein interaction (GK-GKRP) disruptor (IC50: 4 nM).

L-Glucose (L-(-)-Glucose) is an enantiomer of D-glucose. L-Glucose is not bioavailable to cells as an energy source because it cannot be phosphorylated by hexokinase.

Paromomycin (Sulfate Salt) is an aminoglycoside that is active against Gram-negative and many Gram-positive bacteria as well as some protozoa and cestodes. Paromomycin in combination with sodium stibogluconate has proven to be effective in African and Indian VL (visceral leishmaniasis) and improves survival in African VL[3]. PS (Paromomycin Sulfate) is effective for elimination of B. coli without hematological side effects[4]. The activity of phosphoglucose isomerase was slightly inhibited by 10(-3) M paromomycin sulfate while those of hexokinase, phosphofructokinase and glucose-6-phosphate dehydrogenase were not inhibited[5]. In addition, with regard to correlation of endotoxemia with renal impairment, endogenous creatinine clearance and p-aminohippurate clearance were significantly improved (P less than 0.02) in those patients whose endotoxemia disappeared on paromomycin sulfate administration. Paromomycin sulfate seems to be effective in the prevention of endotoxemia and the associated renal impairment in cirrhosis in man[6]. Significantly higher frequencies of resistance to paromomycin, kanamycin, neomycin and tobramycin were observed in S. aureus isolates from PS (paromomycin supplemented) birds. Paromomycin supplementation resulted in resistance to aminoglycosides in bacteria of PS turkeys. Co-selection for resistance to other antimicrobial agents was observed in E. coli isolates[7].

Palmitelaidic Acid (trans-Palmitoleic acid) is one of the most abundant fatty acids in serum and tissue.

Lonidamine (Diclondazolic Acid) is an indazole carboxylic acid derivative, principally inhibiting aerobic glycolytic activity, by its effect on mitochondrially-bound hexokinase (HK).

C-02, a proteolysis-targeting chimera (PROTAC) that combines the hexokinase inhibitor lonidamine with the cereblon ligand thalidomide, effectively induces the degradation of hexokinase 2 in 786-O and PANC-1 cells at a concentration of 20 µM. This compound exhibits cytotoxicity to a range of cancer cells, including 786-O, 4T1, PANC-1, HGC-27, and MCF-7, with IC50 values of 34.07 µM, 5.08 µM, 31.53 µM, 6.11 µM, and 21.65 µM, respectively. Additionally, at 20 µM, C-02 diminishes both the extracellular acidification rate (ECAR) and oxygen consumption rate (OCR) in 4T1 cells, suggesting a suppression of glycolysis and mitochondrial damage. In vivo studies reveal that at a dosage of 50 mg/kg, C-02 not only reduces tumor volume but also promotes intratumoral cytokine accumulation and triggers pyroptosis in a 4T1 murine mammary carcinoma model.

Methyl 2-(3-oxo-2-(pent-2-en-1-yl)cyclopentyl)acetate ((±)-Jasmonic Acid methyl ester)induces the synthesis of proteinase inhibitors in plant leaves. In cancer cells, it suppresses proliferation and induces apoptosis. More specifically, methyl jasmonate inhibits hexokinase that is bound to mitochondria. As hexokinase is overexpressed in cancer cells and contributes to cancer cell growth and survival, methyl jasmonate's disruption of mitochondrial hexokinase activity selectively targets, and kills, cancer cells. Methyl 2-(3-oxo-2-(pent-2-en-1-yl)cyclopentyl)acetate derivatives also have potential as anti-inflammatory agents. Methyl 2-(3-oxo-2-(pent-2-en-1-yl)cyclopentyl)acetate has been primarily detected in urine.

2-Deoxy-D-glucose 6-phosphate disodium, a derivative of glucose analog 2-Deoxy-D-glucose, is synthesized in mammalian cells through hexokinase activity on 2-DG. It functions as a competitive inhibitor of glucose metabolism, specifically obstructing glycolysis by targeting hexokinase.

AM-2394 is an effective and specific Glucokinase agonist (GKA, EC50: 60 nM), which catalyzes the phosphorylation of glucose to glucose-6-phosphate. AM-2394(AM2394) increases the affinity of GK for glucose by approximately 10-fold, exhibits moderate clearance and good oral bioavailability in multiple animal models, and lowers glucose excursion following an oral glucose tolerance test in an ob/ob mouse model of diabetes.

Dorzagliatin (HMS5552) is a dual-acting glucokinase (GK) activator. It also improves glycaemic control and pancreatic β-cell function in type 2 diabetes.

AZD-1656 is a glucokinase activator (GKA) that can cause dose-limiting hypoglycemia in normal animals used in embryofetal development studies and type 2 diabetes.

In cells, D-Glucose 6-phosphate sodium (G6P) is generated when glucose is phosphorylated by hexokinase or glucokinase or by the conversion of glucose-1-phosphate by phosphoglucomutase during glycogenolysis. G6P lies at the beginning of both glycolysis and the pentose phosphate pathways. It also can be stored as glycogen when blood glucose levels are high.