[CAS NO. 591778-70-0] CP-640186hydrochloride
PRODUCTS SPECIFICATIONS [591778-70-0]
DESCRIPTION [591778-70-0]
Overview
| MDL | - |
|---|---|
| Molecular Weight | 522.08 |
| Molecular Formula | C30H36ClN3O3 |
| SMILES | O=C([C@H]1CN(C2CCN(C(C3=C(C=CC=C4)C4=CC5=C3C=CC=C5)=O)CC2)CCC1)N6CCOCC6.Cl |
7 Publications Citing Use of MCE
- [1]J Exp Med. 2021 Dec 6;218(12):e20210639.
- [2]Front Oncol. 2021 Apr 22;11:665763.
- [3]Front Oncol. 2021 Apr 6.
- [4]Nutrients. 2021 May 21;13(6):1740.
- [5]Viruses. 2019 Dec 10;11(12):1145.
- [6]Am J Transl Res. 2019 Nov 15;11(11):7104-7114.
- [7]Department of Microbiology & Immunology. Seoul National University Graduate School. 2015 Aug.
Summary
CP-640186 hydrochloride is an orally active and cell-permeable Acetyl-CoA carboxylase ( ACC ) inhibitor with IC 50 s 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 hydrochloride can also stimulate muscle fatty acid oxidation [1] [2] .
IC50 & Target
IC50: 53 nM (rat liver ACC1) and 61 nM (rat skeletal muscle ACC2) [1]
In Vitro
CP-640186 (20 µM; 48 h) treatment can inhibit H460 cell growth
[3]
.
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
[1]
.
CP-640186 (0.62-1.8 µM; 2 h) treatment inhibits fatty acid synthesis and TG synthesis in HepG2 cells
[1]
.
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Cell Proliferation Assay [3]
| 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 [1]
| Cell Line: | C2C12 cells and muscle strips |
| Concentration: | 0.1 nM-100 µM |
| Incubation Time: | 2 hours |
| Result: |
Stimulated palmitate acid oxidation with an EC
50
of 57 nM and a maximal stimulation of 280% in C2C12 cells.
Stimulated palmitate acid oxidation with an EC 50 of 1.3 μM and a maximal stimulation of 240% in isolated rat epitrochlearis muscle. |
Cell Viability Assay [1]
| 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 EC 50 s of 0.62 μM and 1.8 μM, respecticely. |
In Vivo
CP-640186 (oral gavage; 4.6-21 mg/kg; once) demonstrates acute efficacy
[1]
.
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
[1]
.
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
[1]
.
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
| Animal Model: | Male ob/ob mice [1] |
| 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 ED 50 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 [1] |
| 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 Cl p of 65 ml/min/kg, a V dss of 5 liters/kg, an oral T max of 1.0 h, an oral C max of 345 ng/mL, and an oral AUC 0-∞ of 960 ng•h/mL. |
| Animal Model: | Male ob/ob mice [1] |
| 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 Cl p of 54 ml/min/kg, an oral T max of 0.25 h, an oral C max of 2177 ng/mL, and an oral AUC 0-∞ 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 [1] |
| Dosage: | 100 mg/kg |
| Administration: | Oral gavage; 100 mg/kg; once |
| Result: | Resulted in time-dependent reductions in RQ (a ratio of CO 2 production to O 2 consumption) of up to 64%. |
Appearance
Solid
Shipping
Room temperature in continental US; may vary elsewhere.
Storage
4°C, sealed storage, away from moisture
* In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)
Solvent & Solubility
H 2 O : 50 mg/mL ( 95.77 mM ; Need ultrasonic)
DMSO : ≥ 48 mg/mL ( 91.94 mM )
* "≥" means soluble, but saturation unknown.
Stock Solutions
| Concentration Solvent Mass | 1 mg | 5 mg | 10 mg |
|---|
| 1 mM | 1.9154 mL | 9.5771 mL | 19.1542 mL |
| 5 mM | 0.3831 mL | 1.9154 mL | 3.8308 mL |
| 10 mM | 0.1915 mL | 0.9577 mL | 1.9154 mL |
-
1.
Add each solvent one by one: PBS
Solubility: 100 mg/mL (191.54 mM); Clear solution; Need ultrasonic
-
2.
-
3.
Add each solvent one by one: 10% DMSO >> 90% (20% SBE-β-CD in saline)
Solubility: ≥ 2.5 mg/mL (4.79 mM); Clear solution
-
4.
Add each solvent one by one: 10% DMSO >> 90% corn oil
Solubility: ≥ 2.5 mg/mL (4.79 mM); Clear solution
References
- [1] Harwood HJ Jr, 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 experiment
- [2] Yamashita T, et al. 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] Daniel Hess, et al. 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.