| 产品介绍 |
CP-640186 是一种具有口服活性的、可透过细胞的乙酰-CoA 羧化酶 (ACC) 抑制剂，其对大鼠肝脏 ACC1 和大鼠骨骼肌 ACC2 的 IC50s 分别为 53 nM 和 61 nM。乙酰-CoA羧化酶 (ACC) 是脂肪酸代谢的一个关键酶，能够合成丙二酰-CoA。CP-640186 还可以刺激肌肉脂肪酸的氧化。
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| 生物活性 |
CP-640186 is an orally active and cell-permeable Acetyl-CoA carboxylase (ACC) inhibitor with IC50s of 53 nM and 61 nM for rat liver ACC1 and rat skeletal muscle ACC2 respectively. Acetyl-CoA carboxylase (ACC) is a key enzyme of fatty acid metabolism that enables the synthesis of malonyl-CoA. CP-640186 can also stimulate muscle fatty acid oxidation.
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| 体外研究 |
CP-640186 (20 µM; 48 h) treatment can inhibit H460 cell growth.
CP-640186 (0.1 nM-100 µM; 2 h) treatment increases fatty acid metabolism in a concentration-dependent manner in C2C12 cells and muscle strips.
CP-640186 (0.62-1.8 µM; 2 h) treatment inhibits fatty acid synthesis and TG synthesis in HepG2 cells.
西域 has not independently confirmed the accuracy of these methods. They are for reference only.
Cell Proliferation Assay
| Cell Line: |
Human fibroblasts and H460 cells |
| Concentration: |
20 µM |
| Incubation Time: |
48 hours |
| Result: |
Led to a ∼30% decrease in cell number compared to vehicle-treated controls. |
Cell Viability Assay
| Cell Line: |
C2C12 cells and muscle strips |
| Concentration: |
0.1 nM-100 µM |
| Incubation Time: |
2 hours |
| Result: |
Stimulated palmitate acid oxidation with an EC50 of 57 nM and a maximal stimulation of 280% in C2C12 cells.
Stimulated palmitate acid oxidation with an EC50 of 1.3 μM and a maximal stimulation of 240% in isolated rat epitrochlearis muscle. |
Cell Viability Assay
| Cell Line: |
HepG2 cells |
| Concentration: |
0.62-1.8 µM |
| Incubation Time: |
6 hours |
| Result: |
Inhibited fatty acid synthesis and TG synthesis in HepG2 cells with EC50s of 0.62 μM and 1.8 μM, respecticely. |
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体内研究
(In Vivo) |
CP-640186 (oral gavage; 4.6-21 mg/kg; once) demonstrates acute efficacy.
CP-640186 (intravenous injection and oral gavage; Intravenous dose, 5 mg/kg; oral dose, 10 mg/kg; once) shows lowe drug exposure in the rat than the ob/ob mouse at equal doses.
CP-640186 (oral gavage; 100 mg/kg; once) treatment shows a complete shift from carbohydrate utilization to fatty acid utilization as a source of energy at high exposure level.
西域 has not independently confirmed the accuracy of these methods. They are for reference only.
| Animal Model: |
Male ob/ob mice |
| Dosage: |
4.6-21 mg/kg |
| Administration: |
Oral gavage; 4.6-21 mg/kg; once |
| Result: |
Demonstrated acute efficacy for up to 8 h after oral administration, exhibiting ED50 values of 4.6, 9.7, and 21 mg/kg, at 1, 4, and 8 h, respectively, after treatment. |
| Animal Model: |
Male Sprague-Dawley rats |
| Dosage: |
Intravenous dose, 5 mg/kg; oral dose, 10 mg/kg |
| Administration: |
Intravenous injection and oral gavage; Intravenous dose, 5 mg/kg; oral dose, 10 mg/kg; once |
| Result: |
Showed a plasma half-life of 1.5 h, a bioavailability of 39%, a Clp of 65 ml/min/kg, a Vdss of 5 liters/kg, an oral Tmax of 1.0 h, an oral Cmax of 345 ng/mL, and an oral AUC0-∞ of 960 ng•h/mL. |
| Animal Model: |
Male ob/ob mice |
| Dosage: |
Intravenous dose, 5 mg/kg; oral dose, 10 mg/kg |
| Administration: |
Intravenous injection and oral gavage; Intravenous dose, 5 mg/kg; oral dose, 10 mg/kg; once |
| Result: |
Showed a plasma half-life of 1.1 h, a bioavailability of 50%, a Clp of 54 ml/min/kg, an oral Tmax of 0.25 h, an oral Cmax of 2177 ng/mL, and an oral AUC0-∞ of 3068 ng•h/mL. |
| Animal Model: |
Twenty male Sprague-Dawley rats (350-400 g) fasted and then refed a high sucrose diet for 2 days; additional eight rats fasted for 24 h |
| Dosage: |
100 mg/kg |
| Administration: |
Oral gavage; 100 mg/kg; once |
| Result: |
Resulted in time-dependent reductions in RQ (a ratio of CO2 production to O2 consumption) of up to 64%. |
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| 体内研究 |
CP-640186 (oral gavage; 4.6-21 mg/kg; once) demonstrates acute efficacy.
CP-640186 (intravenous injection and oral gavage; Intravenous dose, 5 mg/kg; oral dose, 10 mg/kg; once) shows lowe drug exposure in the rat than the ob/ob mouse at equal doses.
CP-640186 (oral gavage; 100 mg/kg; once) treatment shows a complete shift from carbohydrate utilization to fatty acid utilization as a source of energy at high exposure level.
西域 has not independently confirmed the accuracy of these methods. They are for reference only.
| Animal Model: |
Male ob/ob mice |
| Dosage: |
4.6-21 mg/kg |
| Administration: |
Oral gavage; 4.6-21 mg/kg; once |
| Result: |
Demonstrated acute efficacy for up to 8 h after oral administration, exhibiting ED50 values of 4.6, 9.7, and 21 mg/kg, at 1, 4, and 8 h, respectively, after treatment. |
| Animal Model: |
Male Sprague-Dawley rats |
| Dosage: |
Intravenous dose, 5 mg/kg; oral dose, 10 mg/kg |
| Administration: |
Intravenous injection and oral gavage; Intravenous dose, 5 mg/kg; oral dose, 10 mg/kg; once |
| Result: |
Showed a plasma half-life of 1.5 h, a bioavailability of 39%, a Clp of 65 ml/min/kg, a Vdss of 5 liters/kg, an oral Tmax of 1.0 h, an oral Cmax of 345 ng/mL, and an oral AUC0-∞ of 960 ng•h/mL. |
| Animal Model: |
Male ob/ob mice |
| Dosage: |
Intravenous dose, 5 mg/kg; oral dose, 10 mg/kg |
| Administration: |
Intravenous injection and oral gavage; Intravenous dose, 5 mg/kg; oral dose, 10 mg/kg; once |
| Result: |
Showed a plasma half-life of 1.1 h, a bioavailability of 50%, a Clp of 54 ml/min/kg, an oral Tmax of 0.25 h, an oral Cmax of 2177 ng/mL, and an oral AUC0-∞ of 3068 ng•h/mL. |
| Animal Model: |
Twenty male Sprague-Dawley rats (350-400 g) fasted and then refed a high sucrose diet for 2 days; additional eight rats fasted for 24 h |
| Dosage: |
100 mg/kg |
| Administration: |
Oral gavage; 100 mg/kg; once |
| Result: |
Resulted in time-dependent reductions in RQ (a ratio of CO2 production to O2 consumption) of up to 64%. |
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|---|
| 体内研究 |
CP-640186 (oral gavage; 4.6-21 mg/kg; once) demonstrates acute efficacy.
CP-640186 (intravenous injection and oral gavage; Intravenous dose, 5 mg/kg; oral dose, 10 mg/kg; once) shows lowe drug exposure in the rat than the ob/ob mouse at equal doses.
CP-640186 (oral gavage; 100 mg/kg; once) treatment shows a complete shift from carbohydrate utilization to fatty acid utilization as a source of energy at high exposure level.
西域 has not independently confirmed the accuracy of these methods. They are for reference only.
| Animal Model: |
Male ob/ob mice |
| Dosage: |
4.6-21 mg/kg |
| Administration: |
Oral gavage; 4.6-21 mg/kg; once |
| Result: |
Demonstrated acute efficacy for up to 8 h after oral administration, exhibiting ED50 values of 4.6, 9.7, and 21 mg/kg, at 1, 4, and 8 h, respectively, after treatment. |
| Animal Model: |
Male Sprague-Dawley rats |
| Dosage: |
Intravenous dose, 5 mg/kg; oral dose, 10 mg/kg |
| Administration: |
Intravenous injection and oral gavage; Intravenous dose, 5 mg/kg; oral dose, 10 mg/kg; once |
| Result: |
Showed a plasma half-life of 1.5 h, a bioavailability of 39%, a Clp of 65 ml/min/kg, a Vdss of 5 liters/kg, an oral Tmax of 1.0 h, an oral Cmax of 345 ng/mL, and an oral AUC0-∞ of 960 ng•h/mL. |
| Animal Model: |
Male ob/ob mice |
| Dosage: |
Intravenous dose, 5 mg/kg; oral dose, 10 mg/kg |
| Administration: |
Intravenous injection and oral gavage; Intravenous dose, 5 mg/kg; oral dose, 10 mg/kg; once |
| Result: |
Showed a plasma half-life of 1.1 h, a bioavailability of 50%, a Clp of 54 ml/min/kg, an oral Tmax of 0.25 h, an oral Cmax of 2177 ng/mL, and an oral AUC0-∞ of 3068 ng•h/mL. |
| Animal Model: |
Twenty male Sprague-Dawley rats (350-400 g) fasted and then refed a high sucrose diet for 2 days; additional eight rats fasted for 24 h |
| Dosage: |
100 mg/kg |
| Administration: |
Oral gavage; 100 mg/kg; once |
| Result: |
Resulted in time-dependent reductions in RQ (a ratio of CO2 production to O2 consumption) of up to 64%. |
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| 性状 | Solid |
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| 溶解性数据 |
In Vitro:
DMSO : 100 mg/mL (205.92 mM; Need ultrasonic)
配制储备液
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浓度
溶剂体积
质量
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1 mg |
5 mg |
10 mg |
| 1 mM |
2.0592 mL |
10.2961 mL |
20.5922 mL |
| 5 mM |
0.4118 mL |
2.0592 mL |
4.1184 mL |
| 10 mM |
0.2059 mL |
1.0296 mL |
2.0592 mL |
*
请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80°C, 6 months; -20°C, 1 month。-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。
In Vivo:
请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照 In Vitro 方式配制澄清的储备液，再依次添加助溶剂：
——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用；
以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶
-
1.
请依序添加每种溶剂： 10% DMSO 40% PEG300 5% Tween-80 45% saline Solubility: ≥ 2.5 mg/mL (5.15 mM); Clear solution
此方案可获得 ≥ 2.5 mg/mL (5.15 mM，饱和度未知) 的澄清溶液。 以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；向上述体系中加入50 μL Tween-80，混合均匀；然后继续加入 450 μL生理盐水定容至 1 mL。
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2.
请依序添加每种溶剂： 10% DMSO 90% (20% SBE-β-CD in saline) Solubility: ≥ 2.5 mg/mL (5.15 mM); Clear solution
此方案可获得 ≥ 2.5 mg/mL (5.15 mM，饱和度未知) 的澄清溶液。 以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL 20% 的 SBE-β-CD 生理盐水水溶液中，混合均匀。
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3.
请依序添加每种溶剂： 10% DMSO 90% corn oil Solubility: ≥ 2.5 mg/mL (5.15 mM); Clear solution
此方案可获得 ≥ 2.5 mg/mL (5.15 mM，饱和度未知) 的澄清溶液，此方案不适用于实验周期在半个月以上的实验。 以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。
*以上所有助溶剂都可在 西域 网站选购。
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| 运输条件 |
Room temperature in continental US; may vary elsewhere.
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| 储存方式 |
| Powder |
-20°C |
3 years |
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4°C |
2 years |
| In solvent |
-80°C |
6 months |
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-20°C |
1 month |
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| 参考文献 | |
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