| Size | Price | Stock | Qty |
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| 100mg |
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| 250mg |
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| Targets |
Canrenone (aldadiene, SC 9376) inhibits corticosteroid biosynthesis by competing with endogenous precursors for mitochondrial hydroxylases, specifically 11β- and 18-hydroxylase, in the rat adrenal gland. [1]
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| ln Vitro |
In a dose-dependent way, canrenone suppresses the synthesis of aldosterone, corticosterone, 18-hydroxydeoxycorticosterone, and 18-hydroxycorticosterone [1]. The effects of canrenone on platelet-derived growth factor-induced cell motility and proliferation are dose-dependent. Na+/H+ exchanger 1 activity generated by platelet-derived growth factor is inhibited by canrenone [2].
In rat adrenal quarters from sodium-deficient rats, Canrenone (10⁻⁴ M) inhibited both basal and potassium-stimulated aldosterone production by 70–85%. Basal aldosterone production was 1.640 ± 0.089 nmol/mg N × 2 h without inhibitor vs. 0.477 ± 0.061 nmol/mg N × 2 h with inhibitor (P < 0.001). Potassium-stimulated (9.4 mM K⁺) aldosterone production was 5.782 ± 0.191 nmol/mg N × 2 h without inhibitor vs. 1.135 ± 0.047 nmol/mg N × 2 h with inhibitor (P < 0.001). [1] In adrenal quarters from normally fed rats, canrenone (10⁻⁴ M) inhibited basal aldosterone production from 0.905 ± 0.039 to 0.144 ± 0.019 nmol/mg N × 2 h (P < 0.001), and potassium-stimulated aldosterone production from 2.114 ± 0.097 to 0.511 ± 0.033 nmol/mg N × 2 h (P < 0.001). [1] Canrenone (5 × 10⁻⁶ to 10⁻⁴ M) produced a dose-dependent inhibition of both corticosterone and aldosterone production in DBA-stimulated adrenal quarters of sodium-deficient rats. [1] In DBA-stimulated adrenal quarters of normally fed rats, canrenone dose-dependently inhibited the production of 18-hydroxydeoxycorticosterone. [1] Canrenone also inhibited the production of 18-hydroxycorticosterone in a dose-dependent manner. [1] Adrenal tissue incubated with canrenone (2 × 10⁻⁴ M) accumulated canrenone at 17.53 nmoles/100 mg wet weight and produced a hydroxylated metabolite (metabolite 2) at 14.18 nmoles/100 mg after 2 hours. [1] The production of canrenone metabolites (metabolites 1 and 2) was reduced when corticosteroid synthesis was simultaneously stimulated by DBA (10⁻⁴ M). [1] Mass spectrometry identified both metabolites as hydroxylation products of canrenone; metabolite 1 showed cleavage of a CH₂OH group, indicating hydroxylation of a methyl group. The hydroxylation sites were assigned to positions 11 and 18. [1] |
| ln Vivo |
The primary active metabolite of spironolactone in rats is canrenone, which has a short half-life. The effects of spironolactone and canrenone on RAAS vary with duration of treatment, suggesting that spironolactone is more effective and canrenone's antimineralocorticoid activity is diminished [3].
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| Cell Assay |
Adrenal quarters from male Wistar rats (160–180 g) were prepared and incubated. Incubations were performed in medium containing either 3.4 or 9.4 mEq/L K⁺. Canrenone was dissolved in absolute ethanol and added to the incubation medium to final concentrations ranging from 5 × 10⁻⁶ M to 10⁻⁴ M; the final ethanol concentration was 69 mM. [1]
After incubation, corticosteroids were extracted, purified by thin-layer chromatography (TLC) using solvent systems I (benzene:acetone:H₂O, 3:2:0.02), II (ethyl acetate:cyclohexane, 4:1), and III (chloroform:methanol:H₂O, 20:1:0.05), and quantified by gas chromatography or fluorimetry. Aldosterone was analyzed by gas chromatography; corticosterone, 18-hydroxydeoxycorticosterone, and 18-hydroxycorticosterone were analyzed by gas chromatography after periodic acid oxidation and methylation with diazomethane. [1] For metabolite analysis, adrenal tissue was sonicated in water after incubation, and canrenone and its metabolites were extracted with benzene, purified by TLC, and quantified fluorimetrically using the method for corticosterone. Mass spectrometry was performed on a Varian MAT CH-7 instrument. [1] |
| Animal Protocol |
Male Wistar rats (AF/Han strain, 160–180 g) were used. Rats were maintained on either a standard diet (sodium 96 mEq/kg, potassium 143 mEq/kg) or a low-sodium diet (sodium 15.7 mEq/kg, potassium 113 mEq/kg) with distilled water ad libitum for 14 days. Rats were killed by decapitation, and adrenal glands were quickly removed, trimmed of fat, and quartered for incubation. No in vivo dosing of Canrenone was performed in this study; all experiments were conducted ex vivo on isolated adrenal tissue. [1]
Male Wistar rats (AF/Han strain, 160–180 g) were used. Rats were maintained on either a standard diet (sodium 96 mEq/kg, potassium 143 mEq/kg) or a low-sodium diet (sodium 15.7 mEq/kg, potassium 113 mEq/kg) with distilled water ad libitum for 14 days. Rats were killed by decapitation, and adrenal glands were quickly removed, trimmed of fat, and quartered for incubation. No in vivo dosing of Canrenone was performed in this study; all experiments were conducted ex vivo on isolated adrenal tissue. [1] |
| ADME/Pharmacokinetics |
Canrenone accumulates in adrenal tissue due to its high lipid solubility and the high lipid content of the adrenal gland. After 2 hours of incubation with 2 × 10⁻⁴ M canrenone, adrenal tissue concentration was 17.53 nmoles/100 mg wet weight. [1]
Canrenone is metabolized in the adrenal gland by hydroxylation at positions 11 and 18, producing more water-soluble metabolites that can be released into the incubation medium. [1] |
| References |
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| Additional Infomation |
Canrenone is a steroidal lactone. Canrenone has been used in research trials for the diagnosis of heart failure. Canrenone is an aldosterone antagonist with potassium-sparing and diuretic effects. Canrenone specifically antagonizes aldosterone on renal mineralocorticoid receptors, thereby increasing sodium excretion and inhibiting potassium excretion. Canrenone is the main active metabolite of spironolactone and potassium canrenoneate. It is a synthetic pregnadiene compound with anti-aldosterone activity.
Canrenone (aldadiene, SC 9376) is the main metabolite of spironolactone and is considered responsible for the therapeutic effects of spironolactone in vivo. It inhibits aldosterone and corticosteroid biosynthesis by competing with endogenous precursors for 11β- and 18-hydroxylase enzymes in adrenal mitochondria. This inhibition is dose-dependent and affects both basal and stimulated steroid production. The accumulation of canrenone in the adrenal cortex may explain the formation of "spironolactone bodies" (concentric lamellar structures in mitochondria) observed during spironolactone therapy. [1] |
| Molecular Formula |
C22H26O6
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|---|---|
| Molecular Weight |
386.44
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| Exact Mass |
340.203
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| CAS # |
976-71-6
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| Related CAS # |
Canrenone-d6;Canrenone-d4
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| PubChem CID |
13789
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| Appearance |
White to light yellow solid powder
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| Density |
1.2±0.1 g/cm3
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| Boiling Point |
541.1±50.0 °C at 760 mmHg
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| Melting Point |
158-160ºC
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| Flash Point |
237.6±30.2 °C
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| Vapour Pressure |
0.0±1.4 mmHg at 25°C
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| Index of Refraction |
1.581
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| LogP |
2.99
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
0
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| Heavy Atom Count |
25
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| Complexity |
719
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| Defined Atom Stereocenter Count |
6
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| SMILES |
C[C@]12CC[C@@H]3[C@]4(CCC(=O)C=C4C=C[C@H]3[C@@H]1CC[C@]12CCC(=O)O1)C
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| InChi Key |
UJVLDDZCTMKXJK-WNHSNXHDSA-N
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| 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
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| Chemical Name |
(8R,9S,10R,13S,14S,17R)-10,13-dimethylspiro[2,8,9,11,12,14,15,16-octahydro-1H-cyclopenta[a]phenanthrene-17,5'-oxolane]-2',3-dione
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| Synonyms |
Aldadiene BRN-0046602 BRN 0046602
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ≥ 100 mg/mL (~293.72 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 3 mg/mL (8.81 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 30.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 3 mg/mL (8.81 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 30.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 3 mg/mL (8.81 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.5877 mL | 12.9386 mL | 25.8772 mL | |
| 5 mM | 0.5175 mL | 2.5877 mL | 5.1754 mL | |
| 10 mM | 0.2588 mL | 1.2939 mL | 2.5877 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT03263962 | COMPLETED | Drug: Canrenone | Cardiac Heart Failure Patients | University of Pavia | 2017-07-13 | |
| NCT04977960 | UNKNOWN STATUS | Drug: Potassium Canrenoate | COVID-19 Acute Respiratory Distress Syndrome | Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico | 2022-09 | Phase 2 |
| NCT00403910 | COMPLETED | Drug: Canrenone | Heart Failure | Heart Care Foundation | 2002-09 | Phase 3 |
| NCT02687178 | COMPLETED | Drug: Canrenone 50 vs canrenone 100 mg | Essential Hypertension | University of Pavia | 2010-10 | Phase 4 |
| NCT03536806 | UNKNOWN STATUS | Drug: Saline 0.9% Drug: Canrenone |
Atrial Fibrillation, Paroxysmal | National Institute of Cardiology, Warsaw, Poland | 2018-06 | Phase 4 |
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