WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 500890
CAS#: 1032823-75-8 (free base)
Description: GSK-1292263 is a novel GPR119 agonist that is currently under development for the treatment of type 2 diabetes. GSK1292263 improves glucose regulation in animal models of diabetes, but has no effect on plasma glucose in type 2 diabetics. Unexpectedly, GSK1292263 lowered fasting LDLc and triglycerides (TG), while increasing HDLc in the diabetic subjects. GSK1292263 has significant effects on plasma lipids and lipoprotein particles in dyslipidemic patients when dosed alone and with atorvastatin.
MedKoo Cat#: 500890
CAS#: 1032823-75-8 (free base)
Chemical Formula: C23H28N4O4S
Exact Mass: 456.18313
Molecular Weight: 456.55782
Elemental Analysis: C, 60.51; H, 6.18; N, 12.27; O, 14.02; S, 7.02
Related CAS #: 1032823-75-8 (free base) 1032824-54-6 (HCl)
Synonym: GSK1292263; GSK 1292263l; GSK-1292263
IUPAC/Chemical Name: 3-isopropyl-5-(4-(((6-(4-(methylsulfonyl)phenyl)pyridin-3-yl)oxy)methyl)piperidin-1-yl)-1,2,4-oxadiazole
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
SMILES Code: O=S(C1=CC=C(C2=CC=C(OCC3CCN(C4=NC(C(C)C)=NO4)CC3)C=N2)C=C1)(C)=O
Appearance: Solid powder
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO, not in water
Shelf Life: >5 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
The following data is based on the product molecular weight 456.55782 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
|Concentration / Solvent Volume / Mass||1 mg||5 mg||10 mg|
|1 mM||1.15 mL||5.76 mL||11.51 mL|
|5 mM||0.23 mL||1.15 mL||2.3 mL|
|10 mM||0.12 mL||0.58 mL||1.15 mL|
|50 mM||0.02 mL||0.12 mL||0.23 mL|
1: Yang JW, Kim HS, Im JH, Kim JW, Jun DW, Lim SC, Lee K, Choi JM, Kim SK, Kang KW. GPR119: a promising target for nonalcoholic fatty liver disease. FASEB J. 2015 Sep 23. pii: fj.15-273771. [Epub ahead of print] PubMed PMID: 26399788.
2: Nunez DJ, Bush MA, Collins DA, McMullen SL, Gillmor D, Apseloff G, Atiee G, Corsino L, Morrow L, Feldman PL. Gut hormone pharmacology of a novel GPR119 agonist (GSK1292263), metformin, and sitagliptin in type 2 diabetes mellitus: results from two randomized studies. PLoS One. 2014 Apr 3;9(4):e92494. doi: 10.1371/journal.pone.0092494. eCollection 2014. PubMed PMID: 24699248; PubMed Central PMCID: PMC3974707.
3: Kang SU. GPR119 agonists: a promising approach for T2DM treatment? A SWOT analysis of GPR119. Drug Discov Today. 2013 Dec;18(23-24):1309-15. doi: 10.1016/j.drudis.2013.09.011. Epub 2013 Sep 20. Review. PubMed PMID: 24060477.
4: Polli JW, Hussey E, Bush M, Generaux G, Smith G, Collins D, McMullen S, Turner N, Nunez DJ. Evaluation of drug interactions of GSK1292263 (a GPR119 agonist) with statins: from in vitro data to clinical study design. Xenobiotica. 2013 Jun;43(6):498-508. doi: 10.3109/00498254.2012.739719. Epub 2012 Dec 21. PubMed PMID: 23256625.
The safety, tolerability, pharmacokinetics and pharmacodynamics of single and multiple oral doses of GSK-1292263 were evaluated in a recently completed randomized, placebo-controlled clinical trial in healthy volunteers (ClinicalTrials.gov Identifier NCT00783549). A total of 69 subjects received single escalating doses of GSK-1292263 (10-400 mg) prior to administration of a 250-mg dose given once daily for 2 and 5 days, which was also evaluated in combination with sitagliptin (100 mg). Treatment with GSK-1292263 at all doses was described as well tolerated, with the most common drug-related effects being mild headache, dizziness, hyperhidrosis, flushing and post-OGTT hypoglycemia. Hypoglycemia was not reported with the 5-day dosing schedule. Pharmacokinetic profiling revealed dose-proportional AUC and Cmax at single lower doses, but not at single higher ones. Following repeated once-daily dosing (5 days), drug accumulation was observed consistent with a mean half-life of 12-18 hours. A dose-dependent increase in glucose AUC(0-3 h) during OGTT was seen in GSK-1292263-treated subjects. The treatment was also associated with an increase in PYY during the prandial periods. Coadministration with sitagliptin led to increases in the plasma concentrations of active GLP-1 but reduced the levels of total GLP-1, GIP and PYY. Sitagliptin affected the exposure to GSK-1292263 (50% increase) but GSK-1292263 did not affect sitagliptin exposure. The data support further evaluation of GSK-1292263 for the treatment of type 2 diabetes (Source: Nunez, D.J. et al. Diabetes [70th Annu Meet Sci Sess Am Diabetes Assoc (ADA) (June 25-29, Orlando) 2010] 2010, 59(Suppl. 1): Abst 80-OR).