PF-04937319 (PF04937319) is a novel and potent glucokinase activator (EC50 = 154.4  μM) with the potential to be used for the treatment of type 2 diabetes mellitus. It was designed to maintain glucose-lowering efficacy while mitigating the risk of hypoglycaemia observed with many other GKAs. PF-04937319 is a glucokinase activator which is under development for the treatment of type 2 diametes mellitus. Glucose-phosphorylating enzyme, glucokinase (GK) plays a major role in glucose homeostasis primarily through its regulatory actions in pancreatic β-cells and liver hepatocytes. Conversion of glucose to glucose-6-phosphate by GK promotes glycogen synthesis in liver hepatocytes, and insulin release in the pancreatic β-cells.

Physicochemical Properties

Molecular Formula	C22H20N6O4
Molecular Weight	432.44
Exact Mass	432.154
CAS #	1245603-92-2
PubChem CID	46916694
Appearance	White to yellow solid powder
Density	1.4±0.1 g/cm3
Index of Refraction	1.667
LogP	1.29
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	8
Rotatable Bond Count	5
Heavy Atom Count	32
Complexity	671
Defined Atom Stereocenter Count	0
InChi Key	MASKQITXHVYVFL-UHFFFAOYSA-N
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)
Chemical Name	N,N-dimethyl-5-[[2-methyl-6-[(5-methylpyrazin-2-yl)carbamoyl]-1-benzofuran-4-yl]oxy]pyrimidine-2-carboxamide
Synonyms	PF 04937319 PF04937319 PF-04937319
HS Tariff Code	2934.99.9001
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)

Biological Activity

References	[1]. Pyridoxine dipharmacophore derivatives as potent glucokinase activators for the treatment of type 2 diabetes mellitus. Sci Rep. 2017 Nov 22;7(1):16072. [2]. Two dose-ranging studies with PF-04937319, a systemic partial activator of glucokinase, as add-on therapy to metformin in adults with type 2 diabetes. Diabetes Obes Metab. 2015 Aug;17(8):751-9.
Additional Infomation	PF-04937319 is under investigation in clinical trial NCT01513928 (A Study To Compare The Pharmacokinetics Of Different Formulations Of PF-04937319 In Healthy Subjects).

Solubility Data

Solubility (In Vitro)

DMSO : ~100 mg/mL (~231.25 mM)

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.