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
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
More Info
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).
Biological target:
GSK-1292263 is an orally available GPR119 agonist with pEC50s of 6.9 and 6.7 for human and rat GPR119, respectively.
In vitro activity:
Another GPR119 agonist used in clinical trials, GSK1292263, also potentiated the anti-proliferative effect of gefitinib on MCF-7 and MDA-MB-231 cells (Additional file 1: Figure S1A and B).
Reference: J Exp Clin Cancer Res. 2018 Nov 29;37(1):295. https://pubmed.ncbi.nlm.nih.gov/30497501/
|
Solvent |
mg/mL |
mM |
| Solubility |
| DMSO |
28.0 |
61.33 |
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.
Preparing Stock Solutions
The following data is based on the
product
molecular weight
456.56
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 |
Formulation protocol:
1. Im JH, Kang KW, Kim SY, Kim YG, An YJ, Park S, Jeong BH, Choi SY, Lee JS, Kang KW. GPR119 agonist enhances gefitinib responsiveness through lactate-mediated inhibition of autophagy. J Exp Clin Cancer Res. 2018 Nov 29;37(1):295. doi: 10.1186/s13046-018-0949-2. Erratum in: J Exp Clin Cancer Res. 2022 May 17;41(1):176. PMID: 30497501; PMCID: PMC6267899.
In vitro protocol:
1. Im JH, Kang KW, Kim SY, Kim YG, An YJ, Park S, Jeong BH, Choi SY, Lee JS, Kang KW. GPR119 agonist enhances gefitinib responsiveness through lactate-mediated inhibition of autophagy. J Exp Clin Cancer Res. 2018 Nov 29;37(1):295. doi: 10.1186/s13046-018-0949-2. Erratum in: J Exp Clin Cancer Res. 2022 May 17;41(1):176. PMID: 30497501; PMCID: PMC6267899.
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.
