| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg |
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| Other Sizes |
| Targets |
G protein-coupled receptor 40 (GPR40) (IC50 = 0.13 μM for inhibiting palmitate-induced Ca²⁺ mobilization; Ki = 0.08 μM for GPR40 binding) [1]
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| ln Vitro |
DC260126 suppresses palmitic acid potentiated glucose-stimulated insulin secretion, decreases GTP-loading and ERK1/2 phosphorylation stimulated by linoleic acid in GPR40-CHO cells, and negatively regulates GPR40 mRNA expression induced by oleic acid in Min6 cells[1].
- DC260126 acts as a selective antagonist of GPR40. It dose-dependently inhibited free fatty acid (FFA)-induced intracellular Ca²⁺ mobilization in GPR40-expressing CHO-K1 cells, with an IC50 of 0.13 μM (detected by FLIPR Ca²⁺ assay) [1] - DC260126 showed no significant affinity for other related GPCRs (e.g., GPR120, GPR41, GPR43) at concentrations up to 10 μM, demonstrating high selectivity for GPR40 [1] - In mouse MIN6 β cells, pretreatment with DC260126 (0.1, 1, 10 μM) dose-dependently protected cells from palmitate-induced apoptosis (detected by Annexin V-FITC/PI staining and TUNEL assay). The apoptotic rate was reduced by ~50% at 10 μM compared with the palmitate-only group [2] - DC260126 (1, 10 μM) inhibited palmitate-induced endoplasmic reticulum (ER) stress in MIN6 cells: downregulated the protein expression of ER stress markers GRP78 and CHOP, and reduced the activation of caspase-3 (detected by Western blot) [2] - DC260126 did not affect the viability of MIN6 cells at concentrations up to 10 μM in the absence of palmitate (detected by MTT assay) [2] |
| Enzyme Assay |
- GPR40 functional assay: CHO-K1 cells stably expressing human GPR40 were seeded in 96-well plates and loaded with a Ca²⁺-sensitive fluorescent dye. After incubation, DC260126 (0.001-10 μM) was added, followed by the addition of palmitate (100 μM) as a GPR40 agonist. Intracellular Ca²⁺ mobilization was measured by a fluorescence microplate reader to calculate the inhibition rate and IC50 value [1]
- GPR40 binding assay: Membranes prepared from GPR40-expressing cells were incubated with [³H]-palmitate (ligand) and different concentrations of DC260126 (0.001-10 μM). After incubation, unbound ligand was removed by filtration, and the bound radioactivity was measured by liquid scintillation counting to determine the Ki value [1] |
| Cell Assay |
- MIN6 β cell culture and treatment: MIN6 cells were cultured in high-glucose DMEM medium. Cells were pretreated with DC260126 (0.1, 1, 10 μM) for 1 hour, then exposed to palmitate (0.5 mM) for 24 hours. Control groups included untreated cells and palmitate-only treated cells [2]
- Cell viability assay: After treatment, MTT reagent was added to MIN6 cells, and absorbance at 570 nm was measured to evaluate cell viability [2] - Apoptosis detection: MIN6 cells were stained with Annexin V-FITC and PI, then analyzed by flow cytometry to determine the apoptotic rate; TUNEL assay was also performed to confirm apoptotic cells [2] - Western blot analysis: MIN6 cells were lysed after treatment, and proteins were extracted. SDS-PAGE electrophoresis, membrane transfer, and incubation with antibodies against GRP78, CHOP, pro-caspase-3, cleaved caspase-3, and β-actin were performed. Bands were visualized and quantified [2] |
| Animal Protocol |
Mice: Male C57BL/KsJ-Lep db (db/db) animals are kept in a 12-hour light-dark cycle at 23°C with free access to water and a regular diet of chow. Nine-week-old male db/db mice are split into four groups (n=6) to examine the dose-dependent effect of DC260126. Using a tail vein injection, mice are given either DC260126 (3, 10, 30 mg/kg) or vehicle (5% DMSO in PBS) once a day for five days. On day five, all mouse groups undergo a 6-hour fast, after which blood samples are taken from the orbital venous plexus and separated by centrifugation to extract serum. Next, an ELISA kit is used to measure the serum insulin concentration. In these long-term studies, eighteen six-week-old male, obese db/db mice are placed into two groups and given either DC260126 (10 mg/kg) or vehicle (5% DMSO in PBS) once a day by tail vein injection for 24 days.
Rats: Zucker rats that are obese and female (fa/fa) are kept in a 12:12 light-dark cycle, given free access to water, and fed a high-fat diet consisting of 15% fat, 1% cholesterol, 0.5% sodium cholate, and 15% sucrose, with the exception of times when they are fasted prior to certain experiments. Based on body weight, two groups of six rats each are created at eight weeks of age. During eight weeks, rats receive intraperitoneal injections of DC260126 (6 mg/kg) or vehicle (propylene glycol) once a day. Periodically, food consumption and body weight are assessed. Following a 12-hour fast at the conclusion of the experiment, blood is drawn from the mice. Adipose, renal, and liver tissues are quickly removed and weighed. For western blotting analysis, liver samples are kept at -80°C after being snap frozen in liquid nitrogen. |
| References |
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| Additional Infomation |
DC260126 is a novel synthetic small molecule GPR40 antagonist, belonging to a group of highly selective novel GPR40 antagonists [1]. The protective effect of DC260126 on MIN6 β cells is achieved by inhibiting GPR40, thereby alleviating palmitate-induced endoplasmic reticulum stress and subsequent mitochondrial-dependent apoptosis [2]. DC260126 has potential research value in exploring the role of GPR40 in FFA-induced β cell dysfunction, which is closely related to type 2 diabetes [2].
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| Molecular Formula |
C₁₆H₁₈FNO₂S
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|---|---|
| Molecular Weight |
307.3834
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| Exact Mass |
307.104
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| Elemental Analysis |
C, 62.52 H, 5.90 F, 6.18 N, 4.56 O, 10.41 S, 10.43
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| CAS # |
346692-04-4
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| PubChem CID |
2843133
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| Appearance |
White to off-white solid powder
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| Density |
1.2±0.1 g/cm3
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| Boiling Point |
423.6±55.0 °C at 760 mmHg
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| Flash Point |
210.0±31.5 °C
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| Vapour Pressure |
0.0±1.0 mmHg at 25°C
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| Index of Refraction |
1.579
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| LogP |
4.95
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
21
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| Complexity |
391
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O=S(C1=CC=C(F)C=C1)(NC2=CC=C(CCCC)C=C2)=O
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| InChi Key |
CNGHPXKWPGIDSK-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C16H18FNO2S/c1-2-3-4-13-5-9-15(10-6-13)18-21(19,20)16-11-7-14(17)8-12-16/h5-12,18H,2-4H2,1H3
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| Chemical Name |
N-(4-butylphenyl)-4-fluorobenzenesulfonamide
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| Synonyms |
DC 260126; DC-260126; DC260126
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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: ~61 mg/mL (~198.5 mM)
Ethanol: ~61 mg/mL |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (8.13 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (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 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (8.13 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (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 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (8.13 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.2533 mL | 16.2665 mL | 32.5330 mL | |
| 5 mM | 0.6507 mL | 3.2533 mL | 6.5066 mL | |
| 10 mM | 0.3253 mL | 1.6267 mL | 3.2533 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.
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