| Size | Price | Stock | Qty |
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| 1mg |
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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 |
| Targets |
Glucokinase (GK).
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|---|---|
| ln Vitro |
Nerigliatin activates glucokinase, the enzyme that catalyzes the conversion of glucose to glucose-6-phosphate. The EC50 is 154.4 µM. This activation enhances glucose-stimulated insulin secretion from pancreatic β-cells and promotes hepatic glucose uptake. The compound is designed to maintain glucose-lowering efficacy while minimizing hypoglycemia risk.
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| ln Vivo |
Nerigliatin decreases fasting plasma glucose levels in preclinical models. In clinical trials, it improved glycemic control in adults with type 2 diabetes when used in conjunction with metformin. The compound maintained lower glucose levels without resulting in hypoglycemia.
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| Enzyme Assay |
In vitro enzyme assays measure glucokinase activity by monitoring glucose-6-phosphate production. Recombinant human glucokinase is incubated with glucose, ATP, and varying concentrations of Nerigliatin (typically 0.1-1000 µM). The reaction is monitored spectrophotometrically at 340 nm using a coupled enzyme system (glucose-6-phosphate dehydrogenase). EC50 values are calculated from activation curves. Selectivity is assessed against other hexokinase isoforms.
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| Cell Assay |
Cellular assays are performed using pancreatic β-cell lines (e.g., MIN6 or INS-1) or primary rodent islets. Cells are treated with Nerigliatin at concentrations ranging from 0.1-1000 µM in the presence of varying glucose concentrations (2-20 mM). Insulin secretion is measured by ELISA or radioimmunoassay. Glucose consumption and lactate production are measured in hepatocyte cultures. Cytotoxicity is assessed using MTT assays.
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| Animal Protocol |
In vivo efficacy is evaluated in diabetic rodent models (e.g., db/db mice or Zucker diabetic fatty rats). Nerigliatin is administered orally at doses ranging from 1-100 mg/kg. Fasting blood glucose is measured at various time points post-dose. Glucose tolerance tests are performed. HbA1c levels are measured after chronic dosing. Pharmacodynamic markers include plasma insulin and glucagon levels.
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| ADME/Pharmacokinetics |
Nerigliatin (PF-04937319) has a molecular weight of 432.4 g/mol. It is orally bioavailable. The compound is soluble in DMSO. Store as a powder at -20°C. Pharmacokinetic parameters include oral bioavailability, plasma half-life, and tissue distribution. The compound is typically formulated for oral administration in preclinical studies.
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| Toxicity/Toxicokinetics |
No detailed toxicity data is publicly available for Nerigliatin. As a research compound and clinical candidate, it has undergone preclinical toxicology assessments including genotoxicity (Ames test, micronucleus assay), cardiac safety (hERG channel inhibition), and repeated-dose toxicity studies in rodents and non-rodents. The compound is for research use only and not for human therapeutic use outside of clinical trials.
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| References |
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| Additional Infomation |
PF-04937319 is being studied in the clinical trial NCT01513928 (a study comparing the pharmacokinetics of different formulations of PF-04937319 in healthy subjects).
Nerigliatin is a research-grade glucokinase activator that was in clinical development for type 2 diabetes. It is not approved for clinical use. Also known as PF-04937319. The compound is supplied as a powder with high purity and should be stored desiccated at -20°C. It is a valuable tool for studying glucose homeostasis and diabetes. |
| Molecular Formula |
C22H20N6O4
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|---|---|
| Molecular Weight |
432.44
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| Exact Mass |
432.154
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| CAS # |
1245603-92-2
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| PubChem CID |
46916694
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| Appearance |
White to yellow solid powder
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| Density |
1.4±0.1 g/cm3
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| Index of Refraction |
1.667
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| LogP |
1.29
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
32
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| Complexity |
671
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
MASKQITXHVYVFL-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C22H20N6O4/c1-12-8-24-19(11-23-12)27-21(29)14-6-17-16(5-13(2)31-17)18(7-14)32-15-9-25-20(26-10-15)22(30)28(3)4/h5-11H,1-4H3,(H,24,27,29)
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| Chemical Name |
N,N-dimethyl-5-[[2-methyl-6-[(5-methylpyrazin-2-yl)carbamoyl]-1-benzofuran-4-yl]oxy]pyrimidine-2-carboxamide
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| Synonyms |
PF 04937319 PF04937319 PF-04937319
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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 |
| 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) |
DMSO : ~100 mg/mL (~231.25 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.78 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. Solubility in Formulation 2: ≥ 2.5 mg/mL (5.78 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.3125 mL | 11.5623 mL | 23.1246 mL | |
| 5 mM | 0.4625 mL | 2.3125 mL | 4.6249 mL | |
| 10 mM | 0.2312 mL | 1.1562 mL | 2.3125 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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