GSK1292263 is a novel and potent GPR119 (G-protein-coupled receptor 119) agonist which has potential for the treatment of type 2 diabetes. It is currently undergoing phase 2 clinical trial for type 2 diabetes. GSK1292263 improves glucose regulation in animal models of diabetes, but has no effect on plasma glucose in type 2 diabetics. GSK1292263 treatment displayed little inhibition towards CYPs (CYP1A2, 2C9, 2C19, 2D6, 3A4), p-GP, OATP1B3, or OCT2. However, GSK1292263 inhibited BCRP and OATP1B1, which are transporters involved in statin disposition 1.
Physicochemical Properties
| Molecular Formula | C23H28N4O4S | |
| Molecular Weight | 456.56 | |
| Exact Mass | 456.183 | |
| CAS # | 1032823-75-8 | |
| Related CAS # | 1032823-75-8;1032824-54-6 (HCl); | |
| PubChem CID | 24996872 | |
| Appearance | White to off-white solid powder | |
| Density | 1.2±0.1 g/cm3 | |
| Boiling Point | 655.1±65.0 °C at 760 mmHg | |
| Flash Point | 350.0±34.3 °C | |
| Vapour Pressure | 0.0±2.0 mmHg at 25°C | |
| Index of Refraction | 1.565 | |
| LogP | 1.67 | |
| Hydrogen Bond Donor Count | 0 | |
| Hydrogen Bond Acceptor Count | 8 | |
| Rotatable Bond Count | 7 | |
| Heavy Atom Count | 32 | |
| Complexity | 685 | |
| Defined Atom Stereocenter Count | 0 | |
| InChi Key | AYJRTVVIBJSSKN-UHFFFAOYSA-N | |
| InChi Code | InChI=1S/C23H28N4O4S/c1-16(2)22-25-23(31-26-22)27-12-10-17(11-13-27)15-30-19-6-9-21(24-14-19)18-4-7-20(8-5-18)32(3,28)29/h4-9,14,16-17H,10-13,15H2,1-3H3 | |
| Chemical Name | 5-[4-[[6-(4-methylsulfonylphenyl)pyridin-3-yl]oxymethyl]piperidin-1-yl]-3-propan-2-yl-1,2,4-oxadiazole | |
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| 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 |
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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) |
Biological Activity
| ln Vitro |
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| ln Vivo | In type 2 diabetic rats, GSK1292263 increases glucose-dependent insulin production, upregulates glucagon-like peptide-1, and promotes glucose homeostasis[2]. | |
| Animal Protocol |
Animal/Disease Models: Male neonatal Streptozotocin (STZ)-induced SD rats (7 weeks of age)[2] Doses: 30 mg/kg Route of Administration: Orally given; one time/day for 2 weeks Experimental Results: The AUC of plasma glucose (AUCPG) in the single treatment of the GSK1292263 group was numerically lower than that of the vehicle group, but the effect was modest . |
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| References |
[1]. GPR119 Agonists: A Novel Strategy for Type 2 Diabetes Treatment. [2]. DS-8500a, an Orally Available G Protein-Coupled Receptor 119 Agonist, Upregulates Glucagon-Like Peptide-1 and Enhances Glucose-Dependent Insulin Secretion and Improves Glucose Homeostasis in Type 2 Diabetic Rats. J Pharmacol Exp The. |
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| Additional Infomation | GSK1292263 has been investigated for the treatment of DIABETES MELLITUS, TYPE 2. |
Solubility Data
| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2 mg/mL (4.38 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 20.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. Solubility in Formulation 2: 30% Propylene glycol , 5% Tween 80 , 65% D5W: 30 mg/mL (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1903 mL | 10.9515 mL | 21.9029 mL | |
| 5 mM | 0.4381 mL | 2.1903 mL | 4.3806 mL | |
| 10 mM | 0.2190 mL | 1.0951 mL | 2.1903 mL |