glucokinase

Glucokinase activator 1 is a liver-directed glucokinase activator (EC50: 34 nM).

Glucokinase Activator 3, a highly potent and complete activator of Glucokinase (GK), exhibits an AC50 value of 38 nM. This compound holds potential for type 2 diabetes research applications.

ARRY-403 is a novel glucokinase activator that reduces fasting and postprandial blood glucose in patients with type 2 diabetes.

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.

AMG-1694, a potent disruptor of the glucokinase–glucokinase regulatory protein (GK-GKRP) complex, operates by promoting the dissociation of this complex, thereby indirectly enhancing GK enzymatic activity with an IC50 of 7 nM. It effectively normalizes blood glucose levels in various rodent diabetes models [1] and lowers blood glucose specifically in diabetic animals without affecting normoglycemic ones. Additionally, AMG-1694 reverses the GKRP-induced inhibition of GK activity and facilitates GK translocation.

(1S,2R)-Globalagliatin is a highly potent glucokinase (GK) activator for the study of type 2 diabetes.

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.

WAY-297848 is a novel glucokinase activator for the prevention or treatment of hyperglycemia, diabetes mellitus, obesity, dyslipidemia, and metabolic syndrome.

GKA-22 is a human glucokinase allosteric activator in the absence of glucose.

Piragliatin, also known as RO4389620, is a glucokinase activator. Piragliatin greatly enhances glucose-induced pancreatic islet respiration and insulin release. Piragliatin lowers plasma glucose both in the postabsorptive state and after a glucose challenge in patients with type 2 diabetes mellitus. Piragliatin has an acute glucose-lowering action in patients with mild type 2 diabetes, mainly mediated through a generalized enhancement of β-cell function and through fasting restricted changes in glucose turnover.

AZD1092 is the glucokinase enzyme activator.

ARRY-403, also known as AMG-151, is an orally available allosteric glucokinase (GK) activator developed for the treatment of type 2 diabetes mellitus (T2DM). ARRY-403 has many favorable physicochemical characteristics and ADME properties (low potential to cause drug–drug interactions (DDIs). ARRY-403 potently activates human glucokinase (GK) in vitro (EC50 = 79 nM at 5 mM glucose), with an S0.5 = 0.93 mM glucose (ARRY-403 at 5 mM) and Vmax = 134% compared to the no activator control. It possesses good in vitro drug-like properties (aqueous solubility, cell permeability, low low potential for drug-drug interactions, low predicted hepatic clearance), and selectivity against broad panels of receptors and enzymes.

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

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

PSN-GK1 is a potent activator of glucokinase (EC50: 0.13 μM).

Sinogliatin, a glucokinase activator, is used potentially for the treatment of type 2 diabetes.

AZD-6370 is a glucokinase activator. AZD-6370 decreases fasting and postprandial glucose in type 2 diabetes mellitus patients with effects influenced by dosing regimen and food. AZD-6370 do not affect the central counterregulatory response to hypoglycemia

GKA50 stimulates insulin release from mouse islets of Langerhans and MIN6 cells. GKA50 shows significant glucose lowering in high fat fed female rats. GKA50 is a potent glucokinase activator (EC50=33 nM at 5 mM glucose).

PF-04991532 is an effective, hepatoselective glucokinase activator. It has EC50s of 80 and 100 nM in human and rat, respectively.

PF-04279405 is a potent and selective glucokinase activator.

AMG-7549 is a disrupter of Glucokinase−Glucokinase Regulatory Protein (GK−GKRP) binding.

LY-2599506 is a novel glucokinase activator.

MK-0941 is an orally active and allosteric glucokinase activator, has potential in the treatment of type 2 diabetes.

LBX192( NVP-LBX192) is a liver-targeted glucokinase activator.

GKA50 quarterhydrate is a potent glucokinase activator with an EC50 value of 33 nM. GKA50 quarterhydrate is a glucose-like activator of β-cell metabolism in rodent and human pancreatic islets and a Ca2+-dependent regulator of insulin secretion. quarterhydrate stimulates insulin secretion in mouse islets and significantly reduces blood glucose in high-fat-fed female rats.

AR453588 is an orally bioavailable anti-diabetic glucokinase activator (EC50: 42 nM) with anti-hyperglycemic activity.

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.

AM-9514 is a novel, potent Glucokinase (GK) activator. AM-9514 showed a favorable combination of in vitro potency, enzyme kinetic properties, acceptable pharmacokinetic profiles in preclinical species, and robust efficacy in a rodent PD model. Glucokinase (GK) activators represent a class of type 2 diabetes therapeutics actively pursued due to the central role that GK plays in regulating glucose homeostasis.

AR453588 hydrochloride is an orally bioavailable anti-diabetic glucokinase activator (EC50: 42 nM) with anti-hyperglycemic activity.

(R)-PF-04991532 is the R-enantiomer of PF-04991532 . PF-04991532 is a potent, hepatoselective glucokinase activator .

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.

GKA-71 is an effective glucokinase activator (GKA).

BMS-820132 is a glucokinase activator (AC50: 29 nM).