DC260126

G protein-coupled receptor 40 (GPR40) (IC50 = 0.13 μM for inhibiting palmitate-induced Ca²⁺ mobilization; Ki = 0.08 μM for GPR40 binding) [1]

DC260126 减少 GPR40-CHO 细胞中亚油酸刺激的 GTP 负载和 ERK1/2 磷酸化，抑制棕榈酸增强的葡萄糖刺激的胰岛素分泌，并负调节 Min6 细胞中油酸诱导的 GPR40 mRNA 表达 [1]。

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- DC260126是GPR40的选择性拮抗剂。它在表达GPR40的CHO-K1细胞中，呈剂量依赖性抑制游离脂肪酸（FFA）诱导的细胞内Ca²⁺动员，IC50为0.13 μM（通过FLIPR Ca²⁺检测法测定）[1]
- 在浓度高达10 μM时，DC260126对其他相关G蛋白偶联受体（如GPR120、GPR41、GPR43）无显著亲和力，显示出对GPR40的高选择性[1]
- 在小鼠MIN6 β细胞中，用DC260126（0.1、1、10 μM）预处理，呈剂量依赖性保护细胞免受棕榈酸诱导的凋亡（通过Annexin V-FITC/PI染色和TUNEL法检测）。与仅棕榈酸处理组相比，10 μM剂量组凋亡率降低约50%[2]
- DC260126（1、10 μM）抑制MIN6细胞中棕榈酸诱导的内质网（ER）应激：下调ER应激标志物GRP78和CHOP的蛋白表达，并减少caspase-3的活化（通过Western blot检测）[2]
- 在无棕榈酸存在的情况下，浓度高达10 μM的DC260126对MIN6细胞活力无影响（通过MTT法检测）[2]

- GPR40功能测定：将稳定表达人GPR40的CHO-K1细胞接种到96孔板中，负载Ca²⁺敏感荧光染料。孵育后，加入DC260126（0.001-10 μM），随后加入棕榈酸（100 μM）作为GPR40激动剂。通过荧光酶标仪检测细胞内Ca²⁺动员，计算抑制率和IC50值[1]
- GPR40结合测定：将来自GPR40表达细胞的膜制剂与[³H]-棕榈酸（配体）和不同浓度的DC260126（0.001-10 μM）孵育。孵育后，通过过滤去除未结合的配体，采用液体闪烁计数法测定结合的放射性，以确定Ki值[1]

- MIN6 β细胞培养与处理：MIN6细胞在高糖DMEM培养基中培养。细胞用DC260126（0.1、1、10 μM）预处理1小时，然后暴露于棕榈酸（0.5 mM）中24小时。对照组包括未处理细胞和仅棕榈酸处理细胞[2]
- 细胞活力测定：处理后，向MIN6细胞中加入MTT试剂，检测570 nm处的吸光度值以评估细胞活力[2]
- 凋亡检测：MIN6细胞用Annexin V-FITC和PI染色后，通过流式细胞术测定凋亡率；同时进行TUNEL法以确认凋亡细胞[2]
- Western blot分析：处理后裂解MIN6细胞并提取蛋白，进行SDS-PAGE电泳、转膜，然后与抗GRP78、CHOP、pro-caspase-3、cleaved caspase-3和β-肌动蛋白（β-actin）抗体孵育，显影并定量条带强度[2]

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.

[1]. A novel class of antagonists for the FFAs receptor GPR40. Biochem Biophys Res Commun. 2009;390(3):557-563.

[2]. Inhibition of GPR40 protects MIN6 β cells from palmitate-induced ER stress and apoptosis [published correction appears in J Cell Biochem. 2013 May;114(5):1216]. J Cell Biochem. 2012;113(4):1152-1158.

- DC260126 is a novel synthetic small-molecule antagonist of GPR40, belonging to a new class of GPR40 antagonists with high selectivity [1]
- The protective effect of DC260126 on MIN6 β cells is mediated by inhibiting GPR40, thereby alleviating palmitate-induced ER stress and subsequent mitochondria-dependent apoptosis [2]
- DC260126 has potential research value for exploring the role of GPR40 in FFA-induced β cell dysfunction, which is relevant to type 2 diabetes mellitus [2]

C₁₆H₁₈FNO₂S

307.3834

307.104

C, 62.52 H, 5.90 F, 6.18 N, 4.56 O, 10.41 S, 10.43

346692-04-4

2843133

White to off-white solid powder

1.2±0.1 g/cm3

423.6±55.0 °C at 760 mmHg

210.0±31.5 °C

0.0±1.0 mmHg at 25°C

1.579

4.95

54.6

1

4

6

21

391

0

O=S(C1=CC=C(F)C=C1)(NC2=CC=C(CCCC)C=C2)=O

CNGHPXKWPGIDSK-UHFFFAOYSA-N

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

N-(4-butylphenyl)-4-fluorobenzenesulfonamide

DC 260126; DC-260126; DC260126

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO: ~61 mg/mL (~198.5 mM)
Ethanol: ~61 mg/mL

配方 1 中的溶解度: ≥ 2.5 mg/mL (8.13 mM) (饱和度未知) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将100 μL 25.0 mg/mL澄清DMSO储备液加入到400 μL PEG300中，混匀；然后向上述溶液中加入50 μL Tween-80，混匀；加入450 μL生理盐水定容至1 mL。
*生理盐水的制备：将 0.9 g 氯化钠溶解在 100 mL ddH₂O中，得到澄清溶液。

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配方 2 中的溶解度: ≥ 2.5 mg/mL (8.13 mM) (饱和度未知) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将 100 μL 25.0 mg/mL澄清DMSO储备液加入900 μL 20% SBE-β-CD生理盐水溶液中，混匀。
*20% SBE-β-CD 生理盐水溶液的制备（4°C，1 周）：将 2 g SBE-β-CD 溶解于 10 mL 生理盐水中，得到澄清溶液。

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配方 3 中的溶解度: ≥ 2.5 mg/mL (8.13 mM) (饱和度未知) in 10% DMSO + 90% Corn Oil (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将 100 μL 25.0 mg/mL 澄清 DMSO 储备液加入到 900 μL 玉米油中并混合均匀。

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请根据您的实验动物和给药方式选择适当的溶解配方/方案：
1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液));
2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方):
10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline);
假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL；
3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例;
4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶;
5、为保证最佳实验结果，工作液请现配现用！
6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们;
7、 以上所有助溶剂都可在 Invivochem.cn网站购买。