| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg | |||
| Other Sizes |
Purity: ≥98%
| Targets |
Glucokinase activator. [1]
LY2608204 targets glucokinase (GK), a key enzyme in glucose metabolism that acts as a glucose sensor in pancreatic β-cells and hepatocytes. It activates glucokinase with an EC50 of 42 nM, enhancing the enzyme's affinity for glucose and increasing glucose phosphorylation. This activation leads to increased insulin secretion from pancreatic β-cells and enhanced glycogen synthesis in the liver. LY2608204 also stimulates glucose metabolism in rat insulinoma INS1-E cells with an EC50 of 579 nM. As a dual-acting glucokinase activator, LY2608204 represents a promising approach for type 2 diabetes therapy by targeting both pancreatic and hepatic glucokinase. |
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| ln Vitro |
LY2608204 activates glucokinase (GK) with EC50 of 42 nM at 10 mM glucose with a concentration dependent manner at lower glucose concentrations. LY2608204 also stimulates glucose metabolism in rat insulinoma INS1-E cells with EC50 of 579 NM.
In vitro studies have demonstrated that LY2608204 activates glucokinase with an EC50 of 42 nM at 10 mM glucose, with a concentration-dependent manner at lower glucose concentrations. It also stimulates glucose metabolism in rat insulinoma INS1-E cells with an EC50 of 579 nM. The compound's activity is glucose-dependent, meaning it is more potent at higher glucose concentrations, which is a desirable feature for an antidiabetic agent as it reduces the risk of hypoglycemia. LY2608204 has been shown to decrease plasma glucose in vitro models, confirming its efficacy as a glucokinase activator. These in vitro findings support the compound's potential as a therapeutic agent for type 2 diabetes. |
| ln Vivo |
LY2608204 decreases plasma glucose in a dose-dependent manner at both fasted and postprandial glucose levels. A maximal lowering of glucose AUC versus the untreated control group is observed with the high dose (30 mg/kg) and represents a 42% decrease. Interpolation of the data show that a 20% glucose AUC decrease occurs at an average LY2608204 concentration of 99 ng/mL (179 nM) in plasma, corresponding to a 6.9 mg/kg LY2608204 dose. The in vivo blood brain barrier permeability of LY2608204 results in a mean brain/plasma ratio of 0.17 five minutes post-dose with a mean total brain level of 0.539 nmol/g.
In vivo studies have demonstrated that LY2608204 decreases plasma glucose in a dose-dependent manner at both fasted and postprandial glucose levels. The compound has shown efficacy in animal models of diabetes, with a 20% glucose AUC decrease occurring at a plasma concentration of 99 ng/mL (179 nM), corresponding to a 6.9 mg/kg dose. LY2608204 also exhibits blood-brain barrier permeability, with a mean brain/plasma ratio of 0.17 five minutes post-dose and a mean total brain level of 0.539 nmol/g. The compound has been evaluated in clinical trials for safety and tolerability in patients with type 2 diabetes. These in vivo findings support the potential of LY2608204 as an oral antidiabetic agent. |
| Enzyme Assay |
Non-cellular enzyme assays for LY2608204 typically involve measuring glucokinase activity in the presence of the compound using purified recombinant glucokinase enzyme. The assay is performed in a buffer system containing glucose, ATP, and a coupling enzyme system to detect glucose-6-phosphate production. LY2608204 is tested at various concentrations to determine its EC50 value for glucokinase activation. The assay is typically conducted at a fixed glucose concentration (e.g., 10 mM) to evaluate the compound's potency. Dose-response curves are generated, and EC50 values are calculated using non-linear regression analysis. These assays may also be performed at varying glucose concentrations to assess the glucose-dependent nature of the activation. The specificity of LY2608204 for glucokinase over other hexokinases can be evaluated using similar assays with different enzyme isoforms.
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| Cell Assay |
In vitro cell-based assays for LY2608204 typically use rat insulinoma INS1-E cells or other pancreatic β-cell lines to assess glucose metabolism and insulin secretion. Cells are cultured in appropriate media and treated with LY2608204 at various concentrations for defined periods. Glucose metabolism is measured by assessing glucose uptake, glucose phosphorylation, or lactate production. Insulin secretion is measured using ELISA or similar immunoassays. The EC50 for stimulation of glucose metabolism in INS1-E cells is 579 nM. Cytotoxicity is assessed using MTT or similar assays to ensure that the observed effects are not due to cell death. LY2608204 is typically dissolved in DMSO and diluted in culture medium, with DMSO controls included to account for solvent effects.
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| Animal Protocol |
Suspended in a 1:1 mixture of solutol/ethanol in a bath sonicator (10% of total volume). The obtained suspension is then diluted with 9 volumes of 10% aqueous solutol solution; 1, 3, 6, 10, 20 and 30 mg/kg; Orally, rats are given a 2 g/kg oral glucose bolus 2 hours after LY2608204 administration. Male Wistar rats at a weight of 225-250 g
In vivo animal studies for LY2608204 typically involve rodent models of diabetes, such as db/db mice or streptozotocin-induced diabetic rats. Animals are administered LY2608204 orally at various doses, and blood glucose levels are measured at multiple time points post-administration. Fasted and postprandial glucose levels are assessed to evaluate the compound's efficacy in both states. Dose-response studies are conducted to determine the minimum effective dose and the maximal efficacy. Pharmacokinetic parameters such as plasma concentration, half-life, and brain penetration are also evaluated. In some studies, glucose tolerance tests are performed to assess the compound's effect on glucose excursion after an oral glucose challenge. Body weight and food intake are monitored throughout the study to assess tolerability. |
| ADME/Pharmacokinetics |
Pharmacokinetic studies of LY2608204 have shown that it is orally bioavailable and exhibits dose-dependent plasma exposure. A 20% glucose AUC decrease occurs at a plasma concentration of 99 ng/mL (179 nM), corresponding to a 6.9 mg/kg dose. LY2608204 exhibits blood-brain barrier permeability with a mean brain/plasma ratio of 0.17 five minutes post-dose and a mean total brain level of 0.539 nmol/g. The compound is soluble in DMSO and ethanol but insoluble in water. Its molecular weight is 559.8 g/mol. LY2608204 has been evaluated in clinical trials for safety and tolerability in patients with type 2 diabetes. Further detailed PK parameters such as half-life, volume of distribution, and clearance are available in the clinical study reports.
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| Toxicity/Toxicokinetics |
Toxicological data for LY2608204 are primarily derived from clinical trials in patients with type 2 diabetes, where safety and tolerability were evaluated. The compound has been shown to be generally well-tolerated in clinical studies, though specific toxicological findings are not detailed in publicly available sources. Preclinical toxicology studies likely included standard assessments of acute and chronic toxicity, genotoxicity, and reproductive toxicity as part of the drug development program. The compound's mechanism of action as a glucokinase activator carries a potential risk of hypoglycemia, which is a key safety concern for this class of drugs. However, the glucose-dependent nature of glucokinase activation by LY2608204 may mitigate this risk. Research-grade LY2608204 is intended for laboratory use only and is not for human consumption.
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| References |
J Biomol Struct Dyn.2019 Jan 11:1-15. doi: 10.1080/07391102.2019.1567391.
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| Additional Infomation |
LY2608204 has been used in trials investigating the treatment of type 2 diabetes.
In this computational study, LY-2608204 showed strong binding affinity to mutant ZnT8 transporter with binding energy of -10.37 kcal/mol via molecular docking. Molecular dynamic simulation (Complex I) revealed that LY-2608204 formed three hydrogen bonds with ALA79, ILE80 and ARG215 (occupancy 78%, 76% and 64% respectively) and nine hydrophobic bonds with CYS75, ALA79, ILE80, CYS200, VAL208, ALA210 and ARG215. The mean RMSD of backbone atoms of Complex I was 1.27 Å and became stable after 80 ns. MM/PBSA calculated final binding energy of -256.453±0.837 kcal/mol. [1] LY2608204 (Globalagliatin) is a novel, potent, and orally active small-molecule glucokinase activator belonging to the glucokinase activator (GKA) class. It activates glucokinase with an EC50 of 42 nM and stimulates glucose metabolism in INS1-E cells with an EC50 of 579 nM. In vivo, it decreases plasma glucose in a dose-dependent manner. LY2608204 has been investigated in clinical trials for the treatment of type 2 diabetes. Its mechanism involves enhancing glucokinase activity in pancreatic β-cells and hepatocytes, leading to increased insulin secretion and glycogen synthesis. The compound exhibits blood-brain barrier permeability. LY2608204 is not approved for clinical use and is strictly a research compound. |
| Molecular Formula |
C28H37N3O3S3
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| Molecular Weight |
559.81
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| Exact Mass |
559.199
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| CAS # |
1234703-40-2
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| Related CAS # |
1234703-40-2;Globalagliatin HCl;
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| PubChem CID |
46832368
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| Appearance |
White to off-white solid powder
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| Density |
1.4±0.1 g/cm3
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| Index of Refraction |
1.658
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| LogP |
4.97
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
10
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| Heavy Atom Count |
37
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| Complexity |
903
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| Defined Atom Stereocenter Count |
2
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| SMILES |
C1CCC(CC1)[C@@H]2C[C@@]2(C3=CC=C(C=C3)S(=O)(=O)C4CC4)C(=O)NC5=NC=C(S5)SCCN6CCCC6
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| InChi Key |
QIIVJLHCZUTGSD-CUBQBAPOSA-N
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| InChi Code |
InChI=1S/C28H37N3O3S3/c32-26(30-27-29-19-25(36-27)35-17-16-31-14-4-5-15-31)28(18-24(28)20-6-2-1-3-7-20)21-8-10-22(11-9-21)37(33,34)23-12-13-23/h8-11,19-20,23-24H,1-7,12-18H2,(H,29,30,32)/t24-,28-/m0/s1
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| Chemical Name |
(1R,2S)-2-cyclohexyl-1-(4-cyclopropylsulfonylphenyl)-N-[5-(2-pyrrolidin-1-ylethylsulfanyl)-1,3-thiazol-2-yl]cyclopropane-1-carboxamide
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| Synonyms |
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.47 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (4.47 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (4.47 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: 1% DMSO +30% polyethylene glycol+1% Tween 80 : 30 mg/mL |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.7863 mL | 8.9316 mL | 17.8632 mL | |
| 5 mM | 0.3573 mL | 1.7863 mL | 3.5726 mL | |
| 10 mM | 0.1786 mL | 0.8932 mL | 1.7863 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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