DrugBank: Aldosterone (DB04630)

targets (1) enzymes (3) transporters (3)

Identification

Name

Aldosterone

Accession Number

DB04630

Type

small molecule

Groups

experimental

Description

A hormone secreted by the adrenal cortex that regulates electrolyte and water balance by increasing the renal retention of sodium and the excretion of potassium. [PubChem]

Structure

Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure

Synonyms

(+)-aldosterone
11beta,21-Dihydroxy-3,20-diketo-4-pregnen-18-al
11beta,21-Dihydroxy-3,20-diketopregn-4-ene-18-al
11beta,21-dihydroxy-3,20-dioxo-4-pregnen-18-al
11beta,21-dihydroxy-3,20-dioxo-pregn-4-ene-18-al
11beta,21-dihydroxy-3,20-dioxopregn-4-en-18-al
11beta,21-Dihydroxypregn-4-ene-3,18,20-trione
18-Aldocorticosterone
18-Formyl-11beta,21-dihydroxy-4-pregnene-3,20-dione
18-Oxocorticosterone
Aldocorten
Aldocortene
Aldocortin
Aldosterona [inn-spanish]
Aldosteronum [inn-latin]
D-aldosterone
Electrocortin
Elektrocortin

Salts

Not Available

Brand names

Not Available

Brand mixtures

Not Available

Categories

Not Available

CAS number

52-39-1

Weight

Average: 360.444
Monoisotopic: 360.193674006

Chemical Formula

C₂₁H₂₈O₅

InChI Key

InChIKey=PQSUYGKTWSAVDQ-ZVIOFETBSA-N

InChI

InChI=1S/C21H28O5/c1-20-7-6-13(24)8-12(20)2-3-14-15-4-5-16(18(26)10-22)21(15,11-23)9-17(25)19(14)20/h8,11,14-17,19,22,25H,2-7,9-10H2,1H3/t14-,15-,16+,17-,19+,20-,21+/m0/s1

Plain Text

IUPAC Name

(1S,2R,10S,11S,14S,15R,17S)-17-hydroxy-14-(2-hydroxyacetyl)-2-methyl-5-oxotetracyclo[8.7.0.0^{2,7}.0^{11,15}]heptadec-6-ene-15-carbaldehyde

SMILES

[H][C@@]1(CC[C@@]2([H])[C@]3([H])CCC4=CC(=O)CC[C@]4(C)[C@@]3([H])[C@@]([H])(O)C[C@]12C=O)C(=O)CO

Plain Text

Mass Spec

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Taxonomy

Kingdom

Not Available

Classes

Not Available

Substructures

Not Available

Pharmacology

Indication

Not Available

Pharmacodynamics

At the late distal tubule and collecting duct, aldosterone has two main actions: 1) aldosterone acts on mineralocorticoid receptors (MR) on principal cells in the distal tubule of the kidney nephron, increasing the permeability of their apical (luminal) membrane to potassium and sodium and activates their basolateral Na+/K+ pumps, stimulating ATP hydrolysis leading to phosphorylation of the pump and a conformational change in the pump exposes the Na+ ions to the outside. The phosphorylated form of the pump has a low affinity for Na+ ions, hence reabsorbing sodium (Na+) ions and water into the blood, and secreting potassium (K+) ions into the urine; 2) aldosterone stimulates H+ secretion by intercalated cells in the collecting duct, regulating plasma bicarbonate (HCO3−) levels and its acid/base balance; and 3) aldosterone may act on the central nervous system via the posterior pituitary gland to release vasopressin (ADH) which serves to conserve water by direct actions on renal tubular resorption.

Mechanism of action

Not Available

Absorption

Not Available

Volume of distribution

Not Available

Protein binding

Not Available

Metabolism

Not Available

Route of elimination

Not Available

Half life

Not Available

Clearance

Not Available

Toxicity

Not Available

Affected organisms

Humans and other mammals

Pathways

Not Available

Pharmacoeconomics

Manufacturers

Not Available

Packagers

Not Available

Dosage forms

Not Available

Prices

Not Available

Patents

Not Available

Properties

State

solid

Experimental Properties

Property	Value	Source
melting point	166.5 °C	PhysProp
water solubility	51.2 mg/L (at 37 °C)	YALKOWSKY,SH & DANNENFELSER,RM (1992)
logP	1.08	HANSCH,C ET AL. (1995)

Predicted Properties

Property	Value	Source
water solubility	1.48e-01 g/l	ALOGPS
logP	1.54	ALOGPS
logP	1.06	ChemAxon
logS	-3.4	ALOGPS
pKa (strongest acidic)	13.82	ChemAxon
pKa (strongest basic)	-2.9	ChemAxon
physiological charge	0	ChemAxon
hydrogen acceptor count	5	ChemAxon
hydrogen donor count	2	ChemAxon
polar surface area	91.67	ChemAxon
rotatable bond count	3	ChemAxon
refractivity	96.79	ChemAxon
polarizability	38.87	ChemAxon

References

Synthesis Reference

Not Available

General Reference

Williams JS, Williams GH: 50th anniversary of aldosterone. J Clin Endocrinol Metab. 2003 Jun;88(6):2364-72. Pubmed

External Links

Resource	Link
KEGG Compound	C01780
PubChem Compound	5839
PubChem Substance	46505770
ChemSpider	5633
ChEBI	27584
ChEMBL	27584
Therapeutic Targets Database	DAP001344
PharmGKB	PA164924487
HET	AS4
Wikipedia	http://en.wikipedia.org/wiki/Aldosterone

ATC Codes

H02AA01

AHFS Codes

Not Available

PDB Entries

Not Available

FDA label

Not Available

MSDS

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Interactions

Drug Interactions

Not Available

Food Interactions

Not Available

Targets
1. Mineralocorticoid receptor Pharmacological action: unknown Receptor for both mineralocorticoids (MC) such as aldosterone and glucocorticoids (GC) such as corticosterone or cortisol. Binds to mineralocorticoid response elements (MRE) and transactivates target genes. The effect of MC is to increase ion and water transport and thus raise extracellular fluid volume and blood pressure and lower potassium levels Organism class: human UniProt ID: P08235 Gene: NR3C2 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: Bruner KL, Derfoul A, Robertson NM, Guerriero G, Fernandes-Alnemri T, Alnemri ES, Litwack G: The unliganded mineralocorticoid receptor is associated with heat shock proteins 70 and 90 and the immunophilin FKBP-52. Recept Signal Transduct. 1997;7(2):85-98. Pubmed Bunda S, Liu P, Wang Y, Liu K, Hinek A: Aldosterone induces elastin production in cardiac fibroblasts through activation of insulin-like growth factor-I receptors in a mineralocorticoid receptor-independent manner. Am J Pathol. 2007 Sep;171(3):809-19. Pubmed Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. Pubmed

Targets

1. Mineralocorticoid receptor

Pharmacological action: unknown

Receptor for both mineralocorticoids (MC) such as aldosterone and glucocorticoids (GC) such as corticosterone or cortisol. Binds to mineralocorticoid response elements (MRE) and transactivates target genes. The effect of MC is to increase ion and water transport and thus raise extracellular fluid volume and blood pressure and lower potassium levels

Organism class: human
UniProt ID: P08235 Link_out

Gene: NR3C2 Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

Bruner KL, Derfoul A, Robertson NM, Guerriero G, Fernandes-Alnemri T, Alnemri ES, Litwack G: The unliganded mineralocorticoid receptor is associated with heat shock proteins 70 and 90 and the immunophilin FKBP-52. Recept Signal Transduct. 1997;7(2):85-98. Pubmed
Bunda S, Liu P, Wang Y, Liu K, Hinek A: Aldosterone induces elastin production in cardiac fibroblasts through activation of insulin-like growth factor-I receptors in a mineralocorticoid receptor-independent manner. Am J Pathol. 2007 Sep;171(3):809-19. Pubmed
Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. Pubmed

Enzymes
1. Cytochrome P450 11B1, mitochondrial Actions: substrate Has steroid 11-beta-hydroxylase activity. In addition to this activity, the 18 or 19-hydroxylation of steroids and the aromatization of androstendione to estrone have also been ascribed to cytochrome P450 XIB UniProt ID: P15538 Gene: CYP11B1 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed 2. Cytochrome P450 11B2, mitochondrial Actions: substrate Preferentially catalyzes the conversion of 11- deoxycorticosterone to aldosterone via corticosterone and 18- hydroxycorticosterone UniProt ID: P19099 Gene: CYP11B2 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed 3. Cytochrome P450 17A1 Actions: inducer Conversion of pregnenolone and progesterone to their 17- alpha-hydroxylated products and subsequently to dehydroepiandrosterone (DHEA) and androstenedione. Catalyzes both the 17-alpha-hydroxylation and the 17,20-lyase reaction. Involved in sexual development during fetal life and at puberty UniProt ID: P05093 Gene: CYP17A1 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

Enzymes

1. Cytochrome P450 11B1, mitochondrial

Actions: substrate

Has steroid 11-beta-hydroxylase activity. In addition to this activity, the 18 or 19-hydroxylation of steroids and the aromatization of androstendione to estrone have also been ascribed to cytochrome P450 XIB

UniProt ID: P15538 Link_out

Gene: CYP11B1 Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

2. Cytochrome P450 11B2, mitochondrial

Actions: substrate

Preferentially catalyzes the conversion of 11- deoxycorticosterone to aldosterone via corticosterone and 18- hydroxycorticosterone

UniProt ID: P19099 Link_out

Gene: CYP11B2 Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

3. Cytochrome P450 17A1

Actions: inducer

Conversion of pregnenolone and progesterone to their 17- alpha-hydroxylated products and subsequently to dehydroepiandrosterone (DHEA) and androstenedione. Catalyzes both the 17-alpha-hydroxylation and the 17,20-lyase reaction. Involved in sexual development during fetal life and at puberty

UniProt ID: P05093 Link_out

Gene: CYP17A1 Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

Transporters
1. Multidrug resistance protein 1 Actions: substrate, inducer Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells UniProt ID: P08183 Gene: ABCB1 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: Romiti N, Tramonti G, Chieli E: Influence of different chemicals on MDR-1 P-glycoprotein expression and activity in the HK-2 proximal tubular cell line. Toxicol Appl Pharmacol. 2002 Sep 1;183(2):83-91. Pubmed Ueda K, Okamura N, Hirai M, Tanigawara Y, Saeki T, Kioka N, Komano T, Hori R: Human P-glycoprotein transports cortisol, aldosterone, and dexamethasone, but not progesterone. J Biol Chem. 1992 Dec 5;267(34):24248-52. Pubmed 2. Organic cation/carnitine transporter 2 Actions: inhibitor Sodium-ion dependent, high affinity carnitine transporter. Involved in the active cellular uptake of carnitine. Transports one sodium ion with one molecule of carnitine. Also transports organic cations such as tetraethylammonium (TEA) without the involvement of sodium. Also Relative uptake activity ratio of carnitine to TEA is 11.3 UniProt ID: O76082 Gene: SLC22A5 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: Ohashi R, Tamai I, Yabuuchi H, Nezu JI, Oku A, Sai Y, Shimane M, Tsuji A: Na(+)-dependent carnitine transport by organic cation transporter (OCTN2): its pharmacological and toxicological relevance. J Pharmacol Exp Ther. 1999 Nov;291(2):778-84. Pubmed 3. Solute carrier organic anion transporter family member 1A2 Actions: inhibitor Mediates the Na(+)-independent transport of organic anions such as sulfobromophthalein (BSP) and conjugated (taurocholate) and unconjugated (cholate) bile acids (By similarity) UniProt ID: P46721 Gene: SLCO1A2 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: Kanai N, Lu R, Bao Y, Wolkoff AW, Schuster VL: Transient expression of oatp organic anion transporter in mammalian cells: identification of candidate substrates. Am J Physiol. 1996 Feb;270(2 Pt 2):F319-25. Pubmed Bossuyt X, Muller M, Hagenbuch B, Meier PJ: Polyspecific drug and steroid clearance by an organic anion transporter of mammalian liver. J Pharmacol Exp Ther. 1996 Mar;276(3):891-6. Pubmed

Transporters

1. Multidrug resistance protein 1

Actions: substrate, inducer

Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells

UniProt ID: P08183 Link_out

Gene: ABCB1 Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

Romiti N, Tramonti G, Chieli E: Influence of different chemicals on MDR-1 P-glycoprotein expression and activity in the HK-2 proximal tubular cell line. Toxicol Appl Pharmacol. 2002 Sep 1;183(2):83-91. Pubmed
Ueda K, Okamura N, Hirai M, Tanigawara Y, Saeki T, Kioka N, Komano T, Hori R: Human P-glycoprotein transports cortisol, aldosterone, and dexamethasone, but not progesterone. J Biol Chem. 1992 Dec 5;267(34):24248-52. Pubmed

2. Organic cation/carnitine transporter 2

Actions: inhibitor

Sodium-ion dependent, high affinity carnitine transporter. Involved in the active cellular uptake of carnitine. Transports one sodium ion with one molecule of carnitine. Also transports organic cations such as tetraethylammonium (TEA) without the involvement of sodium. Also Relative uptake activity ratio of carnitine to TEA is 11.3

UniProt ID: O76082 Link_out

Gene: SLC22A5 Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

Ohashi R, Tamai I, Yabuuchi H, Nezu JI, Oku A, Sai Y, Shimane M, Tsuji A: Na(+)-dependent carnitine transport by organic cation transporter (OCTN2): its pharmacological and toxicological relevance. J Pharmacol Exp Ther. 1999 Nov;291(2):778-84. Pubmed

3. Solute carrier organic anion transporter family member 1A2

Actions: inhibitor

Mediates the Na(+)-independent transport of organic anions such as sulfobromophthalein (BSP) and conjugated (taurocholate) and unconjugated (cholate) bile acids (By similarity)

UniProt ID: P46721 Link_out

Gene: SLCO1A2 Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

Kanai N, Lu R, Bao Y, Wolkoff AW, Schuster VL: Transient expression of oatp organic anion transporter in mammalian cells: identification of candidate substrates. Am J Physiol. 1996 Feb;270(2 Pt 2):F319-25. Pubmed
Bossuyt X, Muller M, Hagenbuch B, Meier PJ: Polyspecific drug and steroid clearance by an organic anion transporter of mammalian liver. J Pharmacol Exp Ther. 1996 Mar;276(3):891-6. Pubmed

Comments

Drug created on September 11, 2007 11:49 / Updated on February 08, 2013 16:23