Synonym
AS1269574; AS-1269574; AS 1269574
IUPAC/Chemical Name
2-[[2-(4-bromophenyl)-6-methylpyrimidin-4-yl]amino]ethanol
InChi Key
DUKPGOOUJNUIOI-UHFFFAOYSA-N
InChi Code
InChI=1S/C13H14BrN3O/c1-9-8-12(15-6-7-18)17-13(16-9)10-2-4-11(14)5-3-10/h2-5,8,18H,6-7H2,1H3,(H,15,16,17)
SMILES Code
CC1=CC(NCCO)=NC(C2=CC=C(Br)C=C2)=N1
Purity
>98% (or refer to the Certificate of Analysis)
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
Shelf Life
>2 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
Biological target:
AS1269574 is a GPR119 agonist, with an EC50 of 2.5 μM in HEK293 cells expressing human GPR119 and activates TRPA1 cation channels to stimulate glucagon-like peptide-1 (GLP-1) secretion.
In vitro activity:
Here, the the preliminary in vitro effects of AS1269574 on insulin secretion and glucose tolerance were examined. To confirm the direct effects of AS1269574 on pancreatic β-cells, we examined GSIS by mouse pancreatic MIN-6 β-cells exposed to AS1269574 at concentrations of 1 and 10 μM. MIN-6 β-cells pre-exposed to 16.8 mM glucose significantly increased insulin secretion when treated with either 1 or 10 μM AS1269574 for 20 min (0.29 ± 0.031 (p < 0.05) and 0.44 ± 0.031 mUnits/20 min (p < 0.01), respectively) compared with the DMSO vehicle control (0.23 ± 0.022 mUnits/20 min). In contrast, AS1269574 had no effect on insulin release by MIN-6 cells under low-glucose (2.8 mM) pre-treatment conditions. Taken together, these results suggest that AS1269574 represents a novel structural class of small molecule GPR119 agonists with GSIS and promising potential for the treatment of type 2 diabetes.
Reference: Biochem Biophys Res Commun. 2010 Sep 24;400(3):437-41. https://pubmed.ncbi.nlm.nih.gov/20804735/
In vivo activity:
The aim was to explore the participation of spinal GPR55 and GPR119 in the processing of neuropathic pain in rats. To confirm the role of spinal GPR55 and GPR119 receptors in the processing of neuropathic pain, increasing doses of the agonist GPR55 (O1602) and the G-protein antagonist peptide were co-administered via intrathecal route with the greatest dose tested of the GPR55 antagonist CID16020046 and the GPR119 agonist AS1269574, respectively. The reduction in the allodynia produced by intrathecal administration of the selective GPR119 agonist AS1269574 (300 μg/rat, i.t.) was reversed, in a dose-dependent manner, with increasing doses of G-protein antagonist peptide (0.001–1 ng/rat, i.t.). G-protein antagonist peptide (1 ng/rat, i.t.) was not able to decrease the 50% paw withdrawal threshold when injected separately, which suggests a selective effect against the activation of spinal GPR119 receptors when co-administered with AS1269574.
Reference: Pharmaceuticals (Basel). 2022 Jan 5;15(1):67. https://pubmed.ncbi.nlm.nih.gov/35056124/
|
Solvent |
mg/mL |
mM |
| Solubility |
| DMSO |
250.0 |
811.24 |
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
308.18
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. Yoshida S, Ohishi T, Matsui T, Shibasaki M. Identification of a novel GPR119 agonist, AS1269574, with in vitro and in vivo glucose-stimulated insulin secretion. Biochem Biophys Res Commun. 2010 Sep 24;400(3):437-41. doi: 10.1016/j.bbrc.2010.08.097. Epub 2010 Sep 16. PMID: 20804735.
2. Chepurny OG, Holz GG, Roe MW, Leech CA. GPR119 Agonist AS1269574 Activates TRPA1 Cation Channels to Stimulate GLP-1 Secretion. Mol Endocrinol. 2016 Jun;30(6):614-29. doi: 10.1210/me.2015-1306. Epub 2016 Apr 15. PMID: 27082897; PMCID: PMC4884340.
3. Zúñiga-Romero Á, Rivera-Plata Q, Arrieta J, Flores-Murrieta FJ, Rodríguez-Silverio J, Reyes-García JG, Huerta-Cruz JC, Ramírez-Martínez G, Rocha-González HI. GPR55 and GPR119 Receptors Contribute to the Processing of Neuropathic Pain in Rats. Pharmaceuticals (Basel). 2022 Jan 5;15(1):67. doi: 10.3390/ph15010067. PMID: 35056124; PMCID: PMC8778754.
In vitro protocol:
1. Yoshida S, Ohishi T, Matsui T, Shibasaki M. Identification of a novel GPR119 agonist, AS1269574, with in vitro and in vivo glucose-stimulated insulin secretion. Biochem Biophys Res Commun. 2010 Sep 24;400(3):437-41. doi: 10.1016/j.bbrc.2010.08.097. Epub 2010 Sep 16. PMID: 20804735.
2. Chepurny OG, Holz GG, Roe MW, Leech CA. GPR119 Agonist AS1269574 Activates TRPA1 Cation Channels to Stimulate GLP-1 Secretion. Mol Endocrinol. 2016 Jun;30(6):614-29. doi: 10.1210/me.2015-1306. Epub 2016 Apr 15. PMID: 27082897; PMCID: PMC4884340.
In vivo protocol:
1. Yoshida S, Ohishi T, Matsui T, Shibasaki M. Identification of a novel GPR119 agonist, AS1269574, with in vitro and in vivo glucose-stimulated insulin secretion. Biochem Biophys Res Commun. 2010 Sep 24;400(3):437-41. doi: 10.1016/j.bbrc.2010.08.097. Epub 2010 Sep 16. PMID: 20804735.
2. . Zúñiga-Romero Á, Rivera-Plata Q, Arrieta J, Flores-Murrieta FJ, Rodríguez-Silverio J, Reyes-García JG, Huerta-Cruz JC, Ramírez-Martínez G, Rocha-González HI. GPR55 and GPR119 Receptors Contribute to the Processing of Neuropathic Pain in Rats. Pharmaceuticals (Basel). 2022 Jan 5;15(1):67. doi: 10.3390/ph15010067. PMID: 35056124; PMCID: PMC8778754.
1: Chepurny OG, Holz GG, Roe MW, Leech CA. GPR119 Agonist AS1269574 Activates TRPA1 Cation Channels to Stimulate GLP-1 Secretion. Mol Endocrinol. 2016 Jun;30(6):614-29. doi: 10.1210/me.2015-1306. PubMed PMID: 27082897; PubMed Central PMCID: PMC4884340.
2: Moran BM, Abdel-Wahab YH, Flatt PR, McKillop AM. Activation of GPR119 by fatty acid agonists augments insulin release from clonal β-cells and isolated pancreatic islets and improves glucose tolerance in mice. Biol Chem. 2014 Apr;395(4):453-64. doi: 10.1515/hsz-2013-0255. PubMed PMID: 24323890.
3: Chepurny OG, Bertinetti D, Diskar M, Leech CA, Afshari P, Tsalkova T, Cheng X, Schwede F, Genieser HG, Herberg FW, Holz GG. Stimulation of proglucagon gene expression by human GPR119 in enteroendocrine L-cell line GLUTag. Mol Endocrinol. 2013 Aug;27(8):1267-82. doi: 10.1210/me.2013-1029. PubMed PMID: 23798572; PubMed Central PMCID: PMC3725342.
4: Yoshida S, Ohishi T, Matsui T, Tanaka H, Oshima H, Yonetoku Y, Shibasaki M. Novel GPR119 agonist AS1535907 contributes to first-phase insulin secretion in rat perfused pancreas and diabetic db/db mice. Biochem Biophys Res Commun. 2010 Nov 12;402(2):280-5. doi: 10.1016/j.bbrc.2010.10.015. PubMed PMID: 20937249.
5: Yoshida S, Tanaka H, Oshima H, Yamazaki T, Yonetoku Y, Ohishi T, Matsui T, Shibasaki M. AS1907417, a novel GPR119 agonist, as an insulinotropic and β-cell preservative agent for the treatment of type 2 diabetes. Biochem Biophys Res Commun. 2010 Oct 1;400(4):745-51. doi: 10.1016/j.bbrc.2010.08.141. PubMed PMID: 20816753.
6: Yoshida S, Ohishi T, Matsui T, Shibasaki M. Identification of a novel GPR119 agonist, AS1269574, with in vitro and in vivo glucose-stimulated insulin secretion. Biochem Biophys Res Commun. 2010 Sep 24;400(3):437-41. doi: 10.1016/j.bbrc.2010.08.097. PubMed PMID: 20804735.
