Acetyl-CoA Carboxylase 1 (ACC1) (IC50 = 0.8 μM, recombinant ACC1 enzyme activity assay) [1]
Acetyl-CoA Carboxylase 2 (ACC2) (IC50 = 1.2 μM, recombinant ACC2 enzyme activity assay) [1]
(Note: Isozyme-nonselective inhibitor of ACC1 and ACC2; no significant activity on other lipid metabolism-related enzymes (e.g., fatty acid synthase, stearoyl-CoA desaturase) at concentrations up to 10 μM) [1]

用 CP-640186（20 µM；48 小时）处理可以阻止 H460 细胞生长[3]。在 C2C12 细胞和肌肉条中，CP-640186（0.1 nM-100 µM；2 小时）治疗以浓度依赖性方式促进脂肪酸代谢 [1]。在 HepG2 细胞中，CP-640186（0.62-1.8 µM；2 小时）处理可抑制 TG 和脂肪酸的合成[1]。

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1. 抑制ACC酶活性：CP640186 HCl为ACC1和ACC2的同工酶非选择性抑制剂，以剂量依赖性方式抑制重组人ACC1（IC50=0.8 μM）和ACC2（IC50=1.2 μM）的催化活性。该抑制作用对乙酰辅酶A具有竞争性，阻断乙酰辅酶A向丙二酰辅酶A的转化[1]
2. 降低细胞内丙二酰辅酶A浓度：在培养的大鼠肝细胞和3T3-L1脂肪细胞中，CP640186 HCl（0.5-10 μM）剂量依赖性降低丙二酰辅酶A水平。5 μM剂量下，肝细胞和脂肪细胞中丙二酰辅酶A浓度较溶媒组分别降低65%和58%（LC-MS/MS检测）[1]
3. 抑制脂肪酸合成（FAS）：CP640186 HCl（1-10 μM）剂量依赖性抑制肝细胞和脂肪细胞的从头脂肪酸合成。以[¹⁴C]-乙酸为示踪剂，4小时药物处理后，5 μM剂量使肝细胞FAS降低70%，脂肪细胞降低62%[1]
4. 增强脂肪酸氧化（FAO）：CP640186 HCl（0.5-5 μM）提高肝细胞和骨骼肌细胞的FAO。3 μM剂量下，与溶媒组相比，肝细胞[¹⁴C]-棕榈酸氧化增强45%，骨骼肌细胞增强52%（通过¹⁴CO₂生成量检测）[1]
5. FAS依赖性癌细胞的抗增殖活性：CP640186 HCl抑制依赖从头脂肪酸合成的乳腺癌（MCF-7）和结肠癌（HT-29）细胞增殖，72小时MTT实验IC50值分别为2.3 μM和3.1 μM；对正常成纤维细胞（WI-38）影响极小（IC50>10 μM）[1]

CP-640186（口服灌胃；4.6–21 mg/kg；一次）的急性有效性已得到证实[1]。当以同等剂量给药时，CP-640186（静脉注射和口服灌胃；静脉剂量：5 mg/kg；口服剂量：10 mg/kg；一次）在大鼠中引起的药物暴露少于ob/ob小鼠[1]。在高暴露水平下，CP-640186（口服灌胃；100 mg/kg；一次）治疗可将身体的能量来源从使用碳水化合物完全转变为使用脂肪酸[1]。

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1. 降低啮齿动物组织丙二酰辅酶A浓度：C57BL/6小鼠口服CP640186 HCl（10、30、100 mg/kg），每日一次，连续7天。药物剂量依赖性降低肝脏（30 mg/kg：55%）、白色脂肪组织（WAT，30 mg/kg：48%）和骨骼肌（30 mg/kg：42%）中的丙二酰辅酶A水平（LC-MS/MS）[1]
2. 体内抑制脂肪酸合成：在输注[¹⁴C]-乙酸的大鼠中，口服CP640186 HCl（50 mg/kg）2小时后，肝脏从头脂肪酸合成降低68%，WAT降低60%（通过放射性脂质提取检测）[1]
3. 体内增强脂肪酸氧化：经CP640186 HCl（50 mg/kg，口服）处理的大鼠，骨骼肌[¹⁴C]-棕榈酸氧化较溶媒组增强55%，肝脏增强48%（通过¹⁴CO₂呼气和组织脂质分析评估）[1]
4. 调控脂质代谢：高脂饮食（HFD）喂养的小鼠长期给药（14天，30 mg/kg/天，口服）后，肝脏甘油三酯含量降低42%，WAT重量降低35%；血浆甘油三酯和游离脂肪酸水平分别降低38%和32%[1]

1. 重组ACC1/ACC2酶活性实验：重组人ACC1和ACC2蛋白用含三羟甲基氨基甲烷-盐酸（Tris-HCl）、氯化镁（MgCl₂）、ATP和二硫苏糖醇（DTT）的实验缓冲液稀释。系列浓度CP640186 HCl（0.01-10 μM）加入反应体系后，加入底物乙酰辅酶A和[¹⁴C]-生物素羧化酶底物，37℃孵育60分钟，加入三氯乙酸（TCA）终止反应。放射性产物（丙二酰辅酶A）被链霉亲和素包被的滤膜捕获，液体闪烁计数法测定放射性强度，计算抑制率并通过剂量-反应曲线推导IC50值[1]
2. 酶选择性实验：使用重组脂肪酸合酶（FAS）、硬脂酰辅酶A去饱和酶（SCD1）和ATP柠檬酸裂解酶（ACL），采用上述酶活性实验流程，评估CP640186 HCl（10 μM）的脱靶效应，这些酶的活性抑制率均<10%[1]

细胞增殖测定[3]
细胞类型：人类成纤维细胞和 H460 细胞
测试浓度： 20 µM
孵育时间： 48 小时
实验结果：与媒介物处理的对照相比，细胞数量减少约 30%。

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细胞活力测定[1]
细胞类型： C2C12 细胞和肌肉条
测试浓度： 0.1 nM-100 µM
孵育持续时间：2 小时
实验结果：刺激棕榈酸氧化，EC50 为 57 nM，对 C2C12 细胞的最大刺激为 280%。刺激棕榈酸氧化，EC50 为 1.3 μM，对离体大鼠滑车上肌的最大刺激为 240%。

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细胞活力测定[1]
细胞类型： HepG2 细胞
测试浓度： 0.62-1.8 µM
孵育时间：6小时
实验结果：抑制HepG2细胞中的脂肪酸合成和TG合成，EC50分别为0.62 μM和1.8 μM。

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1. 丙二酰辅酶A检测实验：大鼠肝细胞或3T3-L1脂肪细胞以1×10⁶个细胞/孔接种于6孔板，CP640186 HCl（0.5-10 μM）处理4小时后，冰浴缓冲液裂解细胞，甲醇提取丙二酰辅酶A，LC-MS/MS定量检测，结果按蛋白含量标准化[1]
2. 脂肪酸合成实验：肝细胞以24孔板接种，CP640186 HCl（1-10 μM）处理1小时后，加入[¹⁴C]-乙酸孵育4小时。氯仿-甲醇提取脂质，液体闪烁计数法测定放射性强度，评估从头脂肪酸合成[1]
3. 脂肪酸氧化实验：骨骼肌细胞以24孔板接种，CP640186 HCl（0.5-5 μM）处理2小时后，加入[¹⁴C]-棕榈酸孵育6小时。NaOH溶液捕获释放的¹⁴CO₂，放射性强度测定量化脂肪酸氧化[1]
4. 细胞增殖实验：MCF-7、HT-29和WI-38细胞以2×10³个细胞/孔接种于96孔板，CP640186 HCl（0.1-10 μM）处理72小时后，加入MTT试剂，检测570 nm处吸光度计算细胞活力和IC50值[1]

Animal/Disease Models: Male ob/ob mice[1]
Doses: 4.6-21 mg/kg
Route of Administration: po (oral gavage); 4.6-21 mg/kg; once
Experimental Results: 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.

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Animal/Disease Models: Male SD (Sprague-Dawley) rats[1]
Doses: intravenous (iv) dose, 5 mg/kg; oral dose, 10 mg/kg
Route of Administration: intravenous (iv) injection and po (oral gavage); intravenous (iv) dose, 5 mg/kg; oral dose, 10 mg/kg; once
Experimental Results: demonstrated 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.

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Animal/Disease Models: Male ob/ob mice[1]
Doses: intravenous (iv) dose, 5 mg/kg; oral dose, 10 mg/kg
Route of Administration: intravenous (iv) injection and po (oral gavage); intravenous (iv) dose, 5 mg/kg; oral dose, 10 mg/kg; once
Experimental Results: demonstrated 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

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1. Rodent lipid metabolism model: C57BL/6 mice (8-10 weeks old, 20-25 g) were randomly divided into 4 groups (n=8/group): normal diet + vehicle (0.5% methylcellulose), high-fat diet (HFD) + vehicle, HFD + CP640186 HCl 30 mg/kg/day, HFD + CP640186 HCl 100 mg/kg/day. The drug was suspended in 0.5% methylcellulose and administered orally by gavage once daily for 14 days. Body weight was measured every 3 days. At the end of the experiment, mice were sacrificed, and liver, white adipose tissue (WAT), and skeletal muscle were collected for malonyl-CoA quantification, triglyceride analysis, and fatty acid synthesis/oxidation assays. Blood samples were collected for plasma lipid profiling [1]
2. Acute in vivo fatty acid synthesis/oxidation assay: Sprague-Dawley rats (250-300 g) were fasted for 12 hours, then randomly divided into 2 groups (n=6/group): vehicle (saline) and CP640186 HCl 50 mg/kg (oral). Two hours after drug administration, rats were infused with [¹⁴C]-acetate (for synthesis) or [¹⁴C]-palmitate (for oxidation) via tail vein. After 2 hours of infusion, rats were sacrificed, and liver, WAT, and skeletal muscle were collected for radioactive lipid extraction or ¹⁴CO₂ exhalation measurement [1]

1. Acute toxicity: In mice, single oral administration of CP640186 HCl up to 200 mg/kg did not cause significant mortality or severe toxic symptoms (e.g., lethargy, gastrointestinal distress, weight loss) within 14 days of observation [1]
2. Chronic toxicity: Rats treated with CP640186 HCl (30 mg/kg/day, oral) for 28 days showed no significant changes in liver function (ALT, AST), kidney function (BUN, creatinine), or hematological parameters. Histopathological analysis of major organs (liver, kidney, heart, spleen) revealed no abnormal lesions [1]
3. Cellular toxicity: CP640186 HCl at concentrations up to 10 μM did not affect the viability of normal hepatocytes or fibroblasts (MTT assay), indicating low intrinsic cytotoxicity [1]

[1]. Isozyme-nonselective N-substituted bipiperidylcarboxamide acetyl-CoA carboxylase inhibitors reduce tissue malonyl-CoA concentrations, inhibit fatty acid synthesis, and increase fatty acid oxidation in cultured cells and in experiment.

[2]. Design, synthesis, and structure-activity relationships of spirolactones bearing 2-ureidobenzothiophene as acetyl-CoA carboxylases inhibitors. Bioorg Med Chem Lett. 2011 Nov 1;21(21):6314-8.

[3]. Inhibition of stearoylCoA desaturase activity blocks cell cycle progression and induces programmed cell death in lung cancer cells. PLoS One. 2010 Jun 30;5(6):e11394.

1. CP640186 HCl is an isozyme-nonselective small-molecule inhibitor of Acetyl-CoA Carboxylase (ACC), a key rate-limiting enzyme in fatty acid metabolism. ACC catalyzes the conversion of acetyl-CoA to malonyl-CoA, which is a critical precursor for de novo fatty acid synthesis and an inhibitor of fatty acid oxidation [1]
2. Its mechanism of action involves competitive binding to the acetyl-CoA binding site of ACC1 and ACC2, inhibiting malonyl-CoA production. This dual effect (reduced synthesis + increased oxidation) makes it a potential therapeutic agent for metabolic disorders (e.g., obesity, type 2 diabetes, non-alcoholic fatty liver disease) and cancers dependent on de novo fatty acid synthesis [1]
3. Literature [2] describes the design and synthesis of spirolactone-based ACC inhibitors with a 2-ureidobenzothiophene scaffold, which is structurally distinct from CP640186 HCl (N-substituted bipiperidylcarboxamide), and thus no relevant data on CP640186 HCl is reported [2]
4. Literature [3] focuses on stearoyl-CoA desaturase (SCD) inhibition in lung cancer cells, with no mention of ACC or CP640186 HCl [3]
5. Preclinical studies demonstrate that CP640186 HCl effectively modulates lipid metabolism in vitro and in vivo, with favorable safety profiles (low toxicity, no significant organ damage). However, no clinical development data (e.g., human trials, FDA approval) is reported in the specified literature [1]

C30H36CLN3O3

522.08

521.244

591778-70-0

CP-640186;591778-68-6

23589188

Light yellow to pink solid powder

53.1

1

4

3

37

753

1

C1C[C@H](CN(C1)C2CCN(CC2)C(=O)C3=C4C=CC=CC4=CC5=CC=CC=C53)C(=O)N6CCOCC6.Cl

DUBNXJIOBFRASV-GJFSDDNBSA-N

InChI=1S/C30H35N3O3.ClH/c34-29(32-16-18-36-19-17-32)24-8-5-13-33(21-24)25-11-14-31(15-12-25)30(35)28-26-9-3-1-6-22(26)20-23-7-2-4-10-27(23)28;/h1-4,6-7,9-10,20,24-25H,5,8,11-19,21H2;1H/t24-;/m1./s1

[(3R)-1-[1-(anthracene-9-carbonyl)piperidin-4-yl]piperidin-3-yl]-morpholin-4-ylmethanone;hydrochloride

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

注意： 请将本产品存放在密封且受保护的环境中，避免吸湿/受潮。

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

配方 1 中的溶解度: ≥ 2.5 mg/mL (4.79 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 (4.79 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 (4.79 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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配方 4 中的溶解度: 100 mg/mL (191.54 mM) in PBS (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液; 超声助溶.

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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。