| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Other Sizes |
Purity: ≥98%
| Targets |
GPR40 ( pIC50 = 6.9 )
GW-1100 targets GPR40/FFA1 (free fatty acid receptor 1), a G-protein coupled receptor activated by long-chain fatty acids such as docosahexaenoic acid (DHA). The compound is a selective antagonist with a pIC50 of 6.9 for GPR40-mediated signaling. |
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| ln Vitro |
GW-1100 (GW1100) dose-inhibitively inhibits the Ca2+ rise mediated by GPR40 stimulated by GW9508 and linoleic acid (pIC50 values of 5.99±0.03 and 5.99±0.06, respectively). GW-1100 at a concentration of 1 μM increased GW9508's There was a significant right shift in the concentration-response curve (pEC50=7.17±0.08 in the absence and pEC50=6.79±0.09 in the presence of 1 μM GW-1100; P<0.05; n=3). At GW-1100 concentrations of 3 μM or higher, a significant decrease in the maximum response was observed and a sustained drift in the pEC50 response [2] was observed. GW-1100 (GW1100) reduces intracellular FFAR1 ligand induction in CHO-K1/bFFAR1 cells and neutrophils CHO-K1/bFFAR1 cells were treated with 10 μM GW1100 or vehicle (0.1% DMSO) for 15 min followed by vehicle , oleic acid, linoleic acid or GW9508 stimulation. GW-1100 was significantly reduced by 300 μM oleic acid (AUC) (60-150 s), p<0.05), 100 μM linoleic acid (AUC (60-150 s), p<0.05) and 10 μM GW9508 (AUC (60-150 s), p<0.05)[3].
In vitro, GW-1100 (1 μM) causes a significant rightward shift in the concentration-response curve of GW9508 (pEC50 from 7.17 to 6.79). At 3 μM and above, it significantly reduces the maximum response. In CHO-K1/bFFAR1 cells, GW-1100 significantly reduces intracellular calcium increases induced by 300 μM oleic acid, 100 μM linoleic acid, and 10 μM GW9508. The compound dose-dependently inhibits GPR40-mediated Ca²⁺ elevations with pIC50 values of 5.99±0.03 and 5.99±0.06 for GW9508 and linoleic acid, respectively. |
| ln Vivo |
Intracerebroventricular injection of DHA (50 μg) and GW9508 (1.0 μg), a GPR40-selective hemostatic agent, significantly reduced mechanical allodynia and thermal hyperalgesia on day 7 after CFA injection, but not GW on day 1. Intraventricular quiescence with -1100 (10 μg), a GPR40 antagonist, inhibits these effects [4].
In vivo, intracerebroventricular injection of GW-1100 (10 μg) inhibits the analgesic effects of DHA (50 μg) and GW9508 (1.0 μg) in a CFA-induced inflammatory pain model. The GPR40 antagonists reduced mechanical and thermal hyperalgesia observed on day 7 post-CFA injection. |
| Enzyme Assay |
For receptor binding and functional assays, cells expressing human GPR40/FFAR1 (e.g., CHO-K1 cells) are loaded with calcium-sensitive dyes. Cells are pre-incubated with GW-1100 and then stimulated with agonists such as GW9508 or linoleic acid. Intracellular calcium changes are measured using fluorometric imaging plate readers (FLIPR) or fluorescence microscopy.
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| Cell Assay |
CHO-K1/pcDNA3 or CHO-K1/bFFAR1.In a recording buffer (10 mM HEPES, 140 mM NaCl, 2 mM CaCl2, 21 mM MgCl2, 25 mM KCl, 10 mM glucose, pH 7.4), 1 cell (2×106 cells/2 mL) is loaded with 2.5 μM Fura-2AM fluorescent indicator dye and left for 30 minutes. The cells are then rinsed three times with the recording buffer and put back into the incubator for 10, minutes. Propionic acid (1, 10 and 30 mM), oleic acid (0-500 μM), linoleic acid (0-200 μM), GW9508 (0-100 μM), ionomycin (2 μM), thapsigargin (2 μM), and vehicle (0.1% DMSO) are all incubated with the cells. The fatty acid concentrations utilized in each experiment fall within the range of what healthy, peripartum cows would normally have. In an additional series of tests, after 15 minutes of incubation with either 10 μM GW-1100, 3 minutes with 2 μM U73122, or 15 minutes with vehicle (0.1% DMSO), cells are stimulated with 300 μM oleic acid, 100 μM linoleic acid, or 10 μM GW9508. With a 340/380 nm dual wavelength excitation, cellular fluorescence (Ca2+) is measured at 509 nm emission using an LS55 spectrofluorimeter. Cuvettes are stirred continuously to maintain a temperature of 37°C[3].
Cellular assays utilize CHO-K1/bFFAR1 cells or HEK-293 cells stably expressing GPR40. Cells are incubated with GW-1100 (typically 0.1-30 μM) for 15 minutes, then stimulated with fatty acids (oleic acid, linoleic acid) or GW9508. Intracellular calcium mobilization is measured using fluorescence-based assays. Inhibition of calcium elevation is calculated to determine pIC50 values. |
| Animal Protocol |
Mice: Male ddY mice, four weeks of age, are kept in cages at 23–24°C with a 12-hour light–dark cycle (lights on from 8 am to 8 pm), as well as unlimited access to food and drink. Before conducting the von Frey test (with a final concentration of 1% DMSO), the following substances are dissolved in 1% DMSO: DHA (50 µg/mouse), the selective GPR40-agonist GW9508 (1.0-25 µg/mouse), and the GPR40 antagonist GW1100 (1-10 µg/mouse). The dosages of GW9508 are determined by our earlier publication, while the selection of GW-1100 is based on our preliminary experiments and earlier reports. DHA and GW9508 are given intracerebroventricular (i.c.v.) 10 minutes prior to CFA injection, and GW1100 is given via the same route 10 minutes prior to GW9508 injection in a non-anesthetized state. After CFA treatment, mice receive intraperitoneal injections of flavopiridol (5 and 15 nmol/mouse), a cyclin-dependent kinase inhibitor, twice daily (at 9:00 and 19:00) into their left lateral ventricle.
In vivo studies are conducted in rodent models of inflammatory pain (e.g., CFA-induced paw inflammation). GW-1100 is administered intracerebroventricularly at 10 μg. Pain behaviors are assessed using von Frey filaments for mechanical allodynia and hot plate or Hargreaves tests for thermal hyperalgesia. The effects of GPR40 agonists (DHA or GW9508) on pain behaviors are evaluated in the presence or absence of GW-1100. |
| ADME/Pharmacokinetics |
GW-1100 (molecular weight 520.58) is a small-molecule GPR40 antagonist. It is soluble in DMSO (30 mg/mL, 57.63 mM) and practically insoluble in water. The compound is typically stored at low temperature and formulated in DMSO for in vitro studies.
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| Toxicity/Toxicokinetics |
Preclinical toxicity studies of GW-1100 have been limited to in vitro and in vivo pharmacology studies. As a GPR40 antagonist, the compound is expected to modulate metabolic pathways involving free fatty acid signaling. No significant toxicity has been reported in the available literature. The compound's safety profile supports its use as a research tool.
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| References |
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| Additional Infomation |
GW-1100 is a selective GPR40/FFAR1 antagonist developed as a research tool for studying the role of free fatty acid receptor 1 in metabolism and pain. Its mechanism involves blocking GPR40-mediated signaling, inhibiting fatty acid-induced calcium mobilization and downstream effects. The compound has been used to demonstrate the involvement of GPR40 in pain modulation and metabolic regulation.
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| Molecular Formula |
C27H25FN4O4S
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|---|---|
| Molecular Weight |
520.5752
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| Exact Mass |
520.158
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| Elemental Analysis |
C, 62.30; H, 4.84; F, 3.65; N, 10.76; O, 12.29; S, 6.16
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| CAS # |
306974-70-9
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| PubChem CID |
11692123
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| Appearance |
White to off-white solid powder
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| Density |
1.3±0.1 g/cm3
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| Boiling Point |
690.2±65.0 °C at 760 mmHg
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| Flash Point |
371.2±34.3 °C
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| Vapour Pressure |
0.0±2.2 mmHg at 25°C
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| Index of Refraction |
1.625
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| LogP |
4.96
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
11
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| Heavy Atom Count |
37
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| Complexity |
832
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O=C1C(CC2=CN=C(N=C2)OCC)=CN(C(SCC3=CC=C(C=C3)F)=N1)C4=CC=C(C(OCC)=O)C=C4
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| InChi Key |
PTPNCCWOTBBVJR-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C27H25FN4O4S/c1-3-35-25(34)20-7-11-23(12-8-20)32-16-21(13-19-14-29-26(30-15-19)36-4-2)24(33)31-27(32)37-17-18-5-9-22(28)10-6-18/h5-12,14-16H,3-4,13,17H2,1-2H3
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| Chemical Name |
ethyl 4-[5-[(2-ethoxypyrimidin-5-yl)methyl]-2-[(4-fluorophenyl)methylsulfanyl]-4-oxopyrimidin-1-yl]benzoate
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| Synonyms |
GW 1100; GW-1100; GW1100
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| HS Tariff Code |
2934.99.9001
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| 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)
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| Solubility (In Vitro) |
DMSO: ~50 mg/mL (~96.1 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: 5 mg/mL (9.60 mM) in 10% DMSO + 40% PEG300 50% PBS (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
Solubility in Formulation 2: ≥ 2.5 mg/mL (4.80 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. View More
Solubility in Formulation 3: 0.06 mg/mL (0.12 mM) in 1% DMSO 99% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.9209 mL | 9.6047 mL | 19.2093 mL | |
| 5 mM | 0.3842 mL | 1.9209 mL | 3.8419 mL | |
| 10 mM | 0.1921 mL | 0.9605 mL | 1.9209 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.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
 Antinociceptive effect of GW9508 and DHA on CFA-induced mechanical allodynia and thermal hyperalgesia.GW9508 (1.0 µg) and DHA (50 µg) i.c.v. administered in CFA-injected mice, whereas GW1100 (10 µg) was administered via the i.c.v. route 10 min before GW9508 or DHA injection;PLoS One. 2013; 8(12): e81563. |
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