产品说明书

CP-640186 HCl

Print
Chemical Structure| 591778-70-0 同义名 : CP-640186 hydrochloride
CAS号 : 591778-70-0
货号 : A695585
分子式 : C30H36ClN3O3
纯度 : 98%+
分子量 : 522.078
MDL号 : MFCD28167776
存储条件：

粉末 Keep in dark place,Inert atmosphere,Room temperature

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 50 mg/mL(95.77 mM)，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO

H2O: 50 mg/mL(95.77 mM)，配合低频超声助溶
动物实验配方：
生物活性
描述 Acetyl-coenzyme A carboxylases (ACCs) are crucial for the metabolism of fatty acids and are promising targets for drug, such as CP-640186 Hydrochloride, development against obesity, diabetes, and other diseases. ACCs catalyzes the conversion of acetyl-CoA to malonyl-CoA. CP-640186 is a novel isozyme-nonselective inhibitor of mammalian ACCs with IC50 values of about 50 nM, including two isoforms of mammalian ACCs and can reduce body weight and improve insulin sensitivity in test animals. It is believed to target the carboxyltransferase (CT) domain of enzymes[3]. Inhibition that induced by CP-640186 hydrochloride was reversible, uncompetitive with respect to ATP, and non-competitive with respect to bicarbonate, acetyl-CoA, and citrate, indicating interaction with the enzymatic carboxyl transfer reaction. In a vitro study, CP-640186 hydrochloride inhibited both rat liver ACC1 and rat skeletal muscle ACC2 with IC50 53 nM and 61 nM, respectively. In a vivo study, mice were given food and water which were treated at a volume of 0.25 ml/25 g of body weight with an aqueous solution containing 0.5% methyl cellulose plus CP-640186 hydrochloride. 1 to 4h after CP-640186 hydrochloride administration, mice were injected with 0.2 ml of [2-14C]acetate then radiolabel test was performed, suggesting that hepatic fatty acid synthesis was inhibited by CP-640186 hydrochloride. Single-dose oral treatment with 100 mg/kg CP-640186 also reduced tissue malonyl-CoA concentrations in chow-fed animals such that liver levels were reduced by 58%, heart levels were reduced by 63%, soleus muscle levels were reduced by 59%, and quadriceps muscle levels were reduced by 80% within 1h of administration[4].
作用机制 CP-640186 hydrochloride is bound in the active site at the interface of a dimer of the carboxyltransferase domain. In other words, CP-640186 hydrochloride has tight interactions with the biotin binding site in the carboxyltransferase domain and three regions for CP-640186 hydrochloride binding in the active site of carboxyltransferase[3].
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

1.92mL

0.38mL

0.19mL

9.58mL

1.92mL

0.96mL

19.15mL

3.83mL

1.92mL
参考文献

[1]Zhang H, Tweel B, et al. Crystal structure of the carboxyltransferase domain of acetyl-coenzyme A carboxylase in complex with CP-640186. Structure. 2004 Sep;12(9):1683-91.

[2]Harwood HJ Jr, Petras SF, et al. 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 experimental animals. J Biol Chem. 2003 Sep 26;278(39):37099-111.

[3]Zhang H, Tweel B, Li J, Tong L. Crystal structure of the carboxyltransferase domain of acetyl-coenzyme A carboxylase in complex with CP-640186. Structure. 2004 Sep;12(9):1683-91.

[4]Harwood HJ Jr, Petras SF, Shelly LD, Zaccaro LM, Perry DA, Makowski MR, Hargrove DM, Martin KA, Tracey WR, Chapman JG, Magee WP, Dalvie DK, Soliman VF, Martin WH, Mularski CJ, Eisenbeis SA. 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 experimental animals. J Biol Chem. 2003 Sep 26;278(39):37099-111.