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MedKoo Cat#: 510292 | Name: CP640186 HCl
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Description:

WARNING: This product is for research use only, not for human or veterinary use.

CP-640186 is a potent inhibitor of mammalian ACCs and can reduce body weight and improve insulin sensitivity in test animals. CP-640186 has recently been shown to be a potent inhibitor of isoforms of mammalian ACCs with IC50 values of about 55 nM. This is currently the only reported potent inhibitor of mammalian ACCs. In cell cultures as well as in animal models, CP-640186 can reduce tissue malonyl-CoA levels, inhibit fatty acid biosynthesis, and stimulate fatty acid oxidation. Most importantly, CP-640186 can reduce body fat mass and body weight, and improve insulin sensitivity, validating ACCs as targets for antiobesity and antidiabetes drugs.

Chemical Structure

CP640186 HCl
CP640186 HCl
CAS#591778-70-0 (HCl)

Theoretical Analysis

MedKoo Cat#: 510292

Name: CP640186 HCl

CAS#: 591778-70-0 (HCl)

Chemical Formula: C30H36ClN3O3

Exact Mass: 0.0000

Molecular Weight: 522.09

Elemental Analysis: C, 69.02; H, 6.95; Cl, 6.79; N, 8.05; O, 9.19

Price and Availability

Size Price Availability Quantity
5mg USD 85.00 Ready to ship
10mg USD 160.00 Ready to ship
25mg USD 350.00 Ready to ship
50mg USD 550.00 Ready to ship
100mg USD 950.00 Ready to ship
200mg USD 1,650.00 Ready to ship
500mg USD 2,950.00 Ready to ship
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Related CAS #
591778-70-0 (HCl) 591778-68-6 (free base)
Synonym
CP640186; CP-640186; CP 640186; CP640,186; CP-640,186; CP 640,186.
IUPAC/Chemical Name
(R)-anthracen-9-yl(3-(morpholine-4-carbonyl)-[1,4'-bipiperidin]-1'-yl)methanone hydrochloride
InChi Key
DUBNXJIOBFRASV-GJFSDDNBSA-N
InChi Code
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
SMILES Code
O=C(C1=C2C=CC=CC2=CC3=CC=CC=C13)N4CCC(N5C[C@H](C(N6CCOCC6)=O)CCC5)CC4.[H]Cl
Appearance
Light yellow solid powder
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO, not in water
Shelf Life
>2 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
More Info
Related CAS# 591778-70-0 (CP-640186 HCl salt); 591778-68-6 (CP-640186 free base).
Biological target:
CP-640186 hydrochloride is a potent 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
In vitro activity:
The reduction in malonyl-CoA levels that occurs in lipogenic tissues after inhibition of ACC1 by CP-640186 leads to a reduction in fatty acid synthesis both in cultured hepatic cells and in lipogenic tissues of experimental animals (see above). The reduction in malonyl-CoA concentration that occurs in oxidative tissues after inhibition of ACC2 by CP-640186 theoretically should lead to a derepression of mitochondrial CPT-1 activity (malonyl-CoA allosterically inhibits CPT-1 (Refs. 18 and 19)) and an increase in fatty acid utilization in these tissues. In this regard, the acute effects of CP-640186 on skeletal muscle fatty acid metabolism ([14C]palmitate oxidation) were assessed in cultured mouse muscle (C2C12) cells and in isolated rat epitrochlearis muscle strips. In both C2C12 cells and muscle strips, CP-640186 increased fatty acid metabolism in a concentration-dependent manner. In C2C12 cells, CP-640186 stimulated [14C]palmitate acid oxidation with an EC50 of 57 nm and a maximal stimulation of 280% (Fig. 5, upper panel). Likewise, in isolated rat epitrochlearis muscle, CP-640186 stimulated [14C]palmitate acid oxidation with an EC50 of 1.3 μm and a maximal stimulation of 240% (Fig. 5, lower panel). These observations indicate that isozyme-nonselective ACC inhibition has the potential to favorably affect risk factors associated with the metabolic syndrome. Reference: 2003 Sep 26;278(39):37099-111. https://pubmed.ncbi.nlm.nih.gov/12842871/
In vivo activity:
To assess changes in malonyl-CoA concentration in these tissues in response to CP-640186 treatment, the method for assessing tissue malonyl-CoA concentration developed by McGarry et al.was adapted to an up to 30 rat/experiment scale (6 groups of 5 animals each). Fasting overnight reduced liver, heart, soleus muscle, and quadriceps muscle malonyl-CoA concentrations by ∼60% (Table III), with no further reduction noted when animals were starved for 48 h (not shown), and refeeding either chow (Table III) or a semi-purified high carbohydrate diet (not shown) for 24 h after an overnight fast returned tissue malonyl-CoA concentrations to initial levels. 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% (p = 0.009), heart levels were reduced by 63% (p = 0.0001), soleus muscle levels were reduced by 59% (p = 0.007), and quadriceps muscle levels were reduced by 80% (p = 0.002) within 1 h of administration (Table III). The reduction in malonyl-CoA concentration induced by CP-640186 in all tissues evaluated was dose-dependent with ED50 values of 6 mg/kg (soleus muscle), 8 mg/kg (cardiac muscle), 15 mg/kg (quadriceps muscle), and 55 mg/kg (liver) noted 1 h after administration (Fig. 4). CP-640186 also increased whole body fatty acid oxidation acutely in chow-fed and in fasted/high carbohydrate diet-refed rats, shifting energy metabolism away from carbohydrate utilization and toward increased fat utilization. hese observations indicate that isozyme-nonselective ACC inhibition has the potential to favorably affect risk factors associated with the metabolic syndrome. Reference: 2003 Sep 26;278(39):37099-111. https://pubmed.ncbi.nlm.nih.gov/12842871/
Solvent mg/mL mM
Solubility
DMSO 39.0 74.70
H2O 50.0 95.77
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 522.09 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol:
1. 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. doi: 10.1074/jbc.M304481200. Epub 2003 Jul 3. PMID: 12842871.
In vitro protocol:
1. 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. doi: 10.1074/jbc.M304481200. Epub 2003 Jul 3. PMID: 12842871.
In vivo protocol:
1. 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. doi: 10.1074/jbc.M304481200. Epub 2003 Jul 3. PMID: 12842871.
1: Yamashita T, Kamata M, Endo S, Yamamoto M, Kakegawa K, Watanabe H, Miwa K, Yamano T, Funata M, Sakamoto J, Tani A, Mol CD, Zou H, Dougan DR, Sang B, Snell G, Fukatsu K. 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. doi: 10.1016/j.bmcl.2011.08.117. Epub 2011 Sep 6. PubMed PMID: 21944854. 2: Hess D, Chisholm JW, Igal RA. 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. doi: 10.1371/journal.pone.0011394. PubMed PMID: 20613975; PubMed Central PMCID: PMC2894866. 3: Xiang S, Callaghan MM, Watson KG, Tong L. A different mechanism for the inhibition of the carboxyltransferase domain of acetyl-coenzyme A carboxylase by tepraloxydim. Proc Natl Acad Sci U S A. 2009 Dec 8;106(49):20723-7. doi: 10.1073/pnas.0908431106. Epub 2009 Nov 19. PubMed PMID: 19926852; PubMed Central PMCID: PMC2791573. 4: Madauss KP, Burkhart WA, Consler TG, Cowan DJ, Gottschalk WK, Miller AB, Short SA, Tran TB, Williams SP. The human ACC2 CT-domain C-terminus is required for full functionality and has a novel twist. Acta Crystallogr D Biol Crystallogr. 2009 May;65(Pt 5):449-61. doi: 10.1107/S0907444909008014. Epub 2009 Apr 18. PubMed PMID: 19390150; PubMed Central PMCID: PMC2725780. 5: Hu HY, Huang YC, Yu HT, Zhang Y. (Anthracen-9-yl)(piperidin-1-yl)-methanone. Acta Crystallogr Sect E Struct Rep Online. 2008 Oct 15;64(Pt 11):o2120. doi: 10.1107/S1600536808033205. PubMed PMID: 21580982; PubMed Central PMCID: PMC2959661. 6: Patil PB, Minteer SD, Mielke AA, Lewis LR, Casmaer CA, Barrientos EJ, Ju JS, Smith JL, Fisher JS. Malonyl coenzyme A affects insulin-stimulated glucose transport in myotubes. Arch Physiol Biochem. 2007 Feb;113(1):13-24. PubMed PMID: 17522981. 7: 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. PubMed PMID: 15341732. 8: 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. Epub 2003 Jul 3. PubMed PMID: 12842871.