CP-640186 hydrochloride

• CAT Number: I006242
• CAS Number: 591778-70-0
• Molecular Formula: C30H36ClN3O3
• Molecular Weight: 522.08
• Purity: ≥95%
• Synonyms: [(3R)-1-[1-(anthracene-9-carbonyl)piperidin-4-yl]piperidin-3-yl]-morpholin-4-ylmethanone;hydrochloride
• InChI: 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
• InChIKey: DUBNXJIOBFRASV-GJFSDDNBSA-N
• SMILES: C1CC(CN(C1)C2CCN(CC2)C(=O)C3=C4C=CC=CC4=CC5=CC=CC=C53)C(=O)N6CCOCC6.Cl

CP-640186 hydrochloride 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 hydrochloride can also stimulate muscle fatty acid oxidation[1][2].
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].
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].

Reference

[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
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[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.
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[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.
 [Content Brief]