Canrenone
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MedKoo CAT#: 540056

CAS#: 976-71-6

Description: Canrenone is a metabolite of spironolactone, Na/K ATPase partial agonist and aldosterone and androgen receptor antagonist used as a diuretic.

Chemical Structure

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Canrenone
CAS# 976-71-6
Product data Instruction

Theoretical Analysis

MedKoo Cat#: 540056
Name: Canrenone
CAS#: 976-71-6
Chemical Formula: C22H28O3
Exact Mass: 340.20
Molecular Weight: 340.460
Elemental Analysis: C, 77.61; H, 8.29; O, 14.10

Price and Availability

Size Price Availability Quantity
1g USD 150 2 Weeks
2g USD 250 2 Weeks
5g USD 550
10g USD 950 2 Weeks
25g USD 1850 2 Weeks
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Synonym: Canrenone; RP 11641; SC 9376; SC-9376; Spirolactone SC 14266; Luvion; NSC 261713; Phanurane; Aldadiene;

IUPAC/Chemical Name: (8R,9S,10R,13S,14S,17R)-10,13-dimethyl-1,3',4',8,9,10,11,12,13,14,15,16-dodecahydro-5'H-spiro[cyclopenta[a]phenanthrene-17,2'-furan]-3,5'(2H)-dione

InChi Key: UJVLDDZCTMKXJK-WNHSNXHDSA-N

InChi Code: InChI=1S/C22H28O3/c1-20-9-5-15(23)13-14(20)3-4-16-17(20)6-10-21(2)18(16)7-11-22(21)12-8-19(24)25-22/h3-4,13,16-18H,5-12H2,1-2H3/t16-,17+,18+,20+,21+,22-/m1/s1

SMILES Code: C[C@]12CCC(=O)C=C1C=C[C@@H]3[C@@H]2CC[C@@]4(C)[C@H]3CC[C@@]45CCC(=O)O5

Appearance: 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

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:

Product Data:
Product Data
Instruction:
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Biological target: Canrenone (Aldadiene) is an aldosterone antagonist extensively used as a diuretic agent.
In vitro activity: Canrenone dose-dependently reduced platelet-derived growth factor-induced cell proliferation and motility. This effect was not associated with either changes in the phosphorylation of platelet-derived growth factor receptor and phospholipase C gamma or in the activation of the Ras/extracellular signal-regulated kinase pathway, whereas it was accompanied by a dose-dependent inhibition of platelet-derived growth factor-induced phosphatidylinositol 3-kinase activity. In addition, canrenone inhibited the activity of the Na(+)/H(+) exchanger 1 induced by platelet-derived growth factor. The effect of canrenone on Na(+)/H(+) exchanger 1 activity was reproduced by phosphatidylinositol 3-kinase inhibitors, thus supporting an inhibitory action of canrenone on phosphatidylinositol 3-kinase activity. To further address this possibility, the action of canrenone was compared with that of 2 established Na(+)/H(+) exchanger 1 inhibitors: ethylisopropylamiloride and cariporide. Whereas ethylisopropylamiloride was able to inhibit platelet-derived growth factor-induced phosphatidylinositol 3-kinase activity, cariporide was without any effect. Both compounds reproduced the effects of canrenone on platelet-derived growth factor-induced mitogenesis and chemotaxis. Finally, canrenone was able to reduce transforming growth factor-beta1-induced de novo synthesis of procollagen type I/IV and fibronectin and thrombin-induced hepatic stellate cell contraction. Reference: Gastroenterology. 2003 Feb;124(2):504-20. https://linkinghub.elsevier.com/retrieve/pii/S0016508502159099
In vivo activity: In this study, the effects of low doses or concentrations of canrenone were investigated in rats by using isolated papillary muscles, Langendorff-perfused hearts, perfused rat-tail vascular bed, and anesthetized animals. Canrenone (0.5, 1, 2, and 5 mg/ml) produced a dose-dependent negative inotropic effect in papillary muscles contracting isometrically and blocked the positive inotropic effect produced by 660 microM ouabain. In Langendorff-perfused hearts beating spontaneously, a low concentration of canrenone (10 microg/ml) increased the isovolumic systolic pressure obtained at several diastolic pressures. Higher concentrations of canrenone (20, 30 microg/ml) brought the isovolumic pressure toward control values, and 100 microg/ml canrenone produced an isovolumic pressure reduction. In these preparations, 20 microg/ml canrenone reduced significantly the positive inotropic effects of 100 microM ouabain. Investigating the vascular smooth muscle reactivity to phenylephrine (PE; 0.5, 1, and 2 microg bolus injections) in the perfused rat-tail vascular bed, it was observed that canrenone blocked completely the enhancement of PE pressor effect produced by 1-h treatment with 100 microM ouabain. Similar results were obtained with the arterial blood pressure reactivity to PE in anesthetized rats. In these animals, canrenone (1 mg/kg) blocked the sensitizing effect of 18 microg/kg ouabain on PE reactivity. In conclusion, results presented here suggest that canrenone may block ouabain effects at very low concentrations. It blocked myocardial positive inotropic effects of ouabain on both papillary muscle and perfused hearts, and the sensitization of PE pressor effects. The results also suggest that canrenone at very small doses might be used to reduce arterial blood pressure in hypertensive conditions accompanied by increased ouabain plasma levels as the main therapeutic procedure or as an adjunct treatment to prevent ouabain sensitizing effects on pressor responses. Reference: J Cardiovasc Pharmacol. 1998 Nov;32(5):679-85. https://doi.org/10.1097/00005344-199811000-00001

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 68.0 199.72

Preparing Stock Solutions

The following data is based on the product molecular weight 340.46 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:
In vitro protocol: 1. Caligiuri A, De Franco RM, Romanelli RG, Gentilini A, Meucci M, Failli P, Mazzetti L, Rombouts K, Geerts A, Vanasia M, Gentilini P, Marra F, Pinzani M. Antifibrogenic effects of canrenone, an antialdosteronic drug, on human hepatic stellate cells. Gastroenterology. 2003 Feb;124(2):504-20. doi: 10.1053/gast.2003.50058. PMID: 12557155.
In vivo protocol: 1. Vassallo PF, Stefanon I, Rossoni LV, França A, Vassallo DV. Small doses of canrenone block the effects of ouabain on the mechanical activity of the heart and vessels of the rat. J Cardiovasc Pharmacol. 1998 Nov;32(5):679-85. doi: 10.1097/00005344-199811000-00001. PMID: 9821839.

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1: Derosa G, Maffioli P, D'Avino M, Sala C, Mugellini A, Vulpis V, Felis S, Guasti L, Sarzani R, Bestetti A, Vanasia M, Gaudio G; ESCAPE-IT Trial Investigators group.. Efficacy and safety of two dosages of canrenone as add-on therapy in hypertensive patients taking ace-inhibitors or angiotensin II receptor blockers and hydrochlorothiazide at maximum dosage in a randomized clinical trial: The ESCAPE-IT trial. Cardiovasc Ther. 2017 Feb;35(1):47-54. doi: 10.1111/1755-5922.12235. PubMed PMID: 27860389.

2: Derosa G, Romano D, Bianchi L, D'Angelo A, Maffioli P. The effects of canrenone on inflammatory markers in patients with metabolic syndrome. Ann Med. 2015 Feb;47(1):47-52. doi: 10.3109/07853890.2014.969303. Epub 2014 Oct 16. PubMed PMID: 25319120.

3: Fogari R, Derosa G, Zoppi A, Lazzari P, D'Angelo A, Mugellini A. Comparative effect of canrenone or hydrochlorothiazide addition to valsartan/amlodipine combination on urinary albumin excretion in well-controlled type 2 diabetic hypertensive patients with microalbuminuria. Expert Opin Pharmacother. 2014 Mar;15(4):453-9. doi: 10.1517/14656566.2014.874415. Epub 2014 Jan 13. PubMed PMID: 24410484.

4: Derosa G, Bonaventura A, Bianchi L, Romano D, D'Angelo A, Fogari E, Maffioli P. Effects of canrenone in patients with metabolic syndrome. Expert Opin Pharmacother. 2013 Nov;14(16):2161-9. doi: 10.1517/14656566.2013.832756. Epub 2013 Aug 28. PubMed PMID: 23984806.

5: Armanini D, Sabbadin C, Donà G, Clari G, Bordin L. Aldosterone receptor blockers spironolactone and canrenone: two multivalent drugs. Expert Opin Pharmacother. 2014 May;15(7):909-12. doi: 10.1517/14656566.2014.896901. Epub 2014 Mar 11. PubMed PMID: 24617854.

6: Dasgupta A, Johnson MJ, Sengupta TK. Clinically insignificant negative interferences of spironolactone, potassium canrenoate, and their common metabolite canrenone in new dimension vista LOCI digoxin immunoassay. J Clin Lab Anal. 2012 May;26(3):143-7. doi: 10.1002/jcla.21501. PubMed PMID: 22628228.

7: Suyagh M, Hawwa AF, Collier PS, Millership JS, Kole P, Millar M, Shields MD, Halliday HL, McElnay JC. Population pharmacokinetic model of canrenone after intravenous administration of potassium canrenoate to paediatric patients. Br J Clin Pharmacol. 2012 Nov;74(5):864-72. doi: 10.1111/j.1365-2125.2012.04257.x. PubMed PMID: 22376078; PubMed Central PMCID: PMC3495151.

8: DeFrance A, Armbruster D, Petty D, Cooper KC, Dasgupta A. Abbott ARCHITECT clinical chemistry and immunoassay systems: digoxin assays are free of interferences from spironolactone, potassium canrenoate, and their common metabolite canrenone. Ther Drug Monit. 2011 Feb;33(1):128-31. doi: 10.1097/FTD.0b013e3181fd4c30. PubMed PMID: 21079546.

9: Huang DM, Zhang TZ, Cui FJ, Sun WJ, Zhao LM, Yang MY, Wang YJ. Simultaneous identification and quantification of canrenone and 11-α-hydroxy-canrenone by LC-MS and HPLC-UVD. J Biomed Biotechnol. 2011;2011:917232. doi: 10.1155/2011/917232. Epub 2011 Dec 13. PubMed PMID: 22203787; PubMed Central PMCID: PMC3238810.

10: Knights KM, Bowalgaha K, Miners JO. Spironolactone and canrenone inhibit UGT2B7-catalyzed human liver and kidney microsomal aldosterone 18beta-glucuronidation: a potential drug interaction. Drug Metab Dispos. 2010 Jul;38(7):1011-4. doi: 10.1124/dmd.110.032870. Epub 2010 Mar 19. PubMed PMID: 20304966.

11: de Simone G, Chinali M, Mureddu GF, Cacciatore G, Lucci D, Latini R, Masson S, Vanasia M, Maggioni AP, Boccanelli A; AREA-in-CHF Investigators.. Effect of canrenone on left ventricular mechanics in patients with mild systolic heart failure and metabolic syndrome: the AREA-in-CHF study. Nutr Metab Cardiovasc Dis. 2011 Oct;21(10):783-91. doi: 10.1016/j.numecd.2010.02.012. Epub 2010 Jun 17. PubMed PMID: 21939839.

12: Dasgupta A, Johnson MJ. Effect of spironolactone, potassium canrenoate, and their common metabolite canrenone on Dimension Vista Digoxin Assay. J Clin Lab Anal. 2010;24(6):413-7. doi: 10.1002/jcla.20421. PubMed PMID: 21089173.

13: Fiore C, Sartorato P, Pagnin E, Ragazzi E, Calò LA, Armanini D. Effect of canrenone and amiloride on the prooxidative effect induced by aldosterone in human mononuclear leukocytes in vitro. J Endocrinol Invest. 2009 Dec;32(11):895-8. doi: 10.3275/6299. Epub 2009 May 21. PubMed PMID: 19509473.

14: Costa AR, Torres LB, Medei E, Ricardo RA, França JP, Smaili S, Nascimento JH, Oshiro ME, Bassani JW, Ferreira AT, Tucci PJ. The negative inotropic action of canrenone is mediated by L-type calcium current blockade and reduced intracellular calcium transients. Br J Pharmacol. 2009 Sep;158(2):580-7. doi: 10.1111/j.1476-5381.2009.00329.x. Epub 2009 Aug 6. PubMed PMID: 19663883; PubMed Central PMCID: PMC2757698.

15: Boccanelli A, Mureddu GF, Cacciatore G, Clemenza F, Di Lenarda A, Gavazzi A, Porcu M, Latini R, Lucci D, Maggioni AP, Masson S, Vanasia M, de Simone G; AREA IN-CHF Investigators.. Anti-remodelling effect of canrenone in patients with mild chronic heart failure (AREA IN-CHF study): final results. Eur J Heart Fail. 2009 Jan;11(1):68-76. doi: 10.1093/eurjhf/hfn015. PubMed PMID: 19147459.

16: Sora DI, Udrescu S, Albu F, David V, Medvedovici A. Analytical issues in HPLC/MS/MS simultaneous assay of furosemide, spironolactone and canrenone in human plasma samples. J Pharm Biomed Anal. 2010 Sep 5;52(5):734-40. doi: 10.1016/j.jpba.2010.03.004. Epub 2010 Mar 7. PubMed PMID: 20307949.

17: Voicu V, Gheorghe MC, Sora ID, Sârbu C, Medvedovici A. Incurred sample reanalysis: different evaluation approaches on data obtained for spironolactone and its active metabolite canrenone. Bioanalysis. 2011 Jun;3(12):1343-56. doi: 10.4155/bio.11.83. PubMed PMID: 21679029.

18: Suyagh MF, Kole PL, Millership J, Collier P, Halliday H, McElnay JC. Development and validation of a dried blood spot-LC-APCI-MS assay for estimation of canrenone in paediatric samples. J Chromatogr B Analyt Technol Biomed Life Sci. 2010 Mar 15;878(9-10):769-76. doi: 10.1016/j.jchromb.2010.01.031. Epub 2010 Feb 1. PubMed PMID: 20153705.

19: Dasgupta A, Tso G, Wells A. Effect of spironolactone, potassium canrenoate and their common metabolite canrenone on serum digoxin measurement by digoxin III, a new digoxin immunoassay. Ther Drug Monit. 2008 Dec;30(6):744-7. doi: 10.1097/FTD.0b013e31818b0e6a. PubMed PMID: 18824952.

20: Bosone D, Costa A, Ghiotto N, Ramusino MC, Zoppi A, D'Angelo A, Fogari R. Effect of ramipril/hydrochlorothiazide and ramipril/canrenone combination on atrial fibrillation recurrence in hypertensive type 2 diabetic patients with and without cardiac autonomic neuropathy. Arch Med Sci. 2017 Apr 1;13(3):550-557. doi: 10.5114/aoms.2016.62448. Epub 2016 Sep 22. PubMed PMID: 28507568; PubMed Central PMCID: PMC5420627.