General Information of Drug (ID: DM9S2JW)

Drug Name
Aldosterone
Synonyms
ALDOSTERONE; 52-39-1; Electrocortin; Aldocortin; Aldocortene; Aldocorten; (+)-Aldosterone; Elektrocortin; d-Aldosterone; Reichstein X; 18-Oxocorticosterone; Aldosteronum; Aldosterona; Aldosteronum [INN-Latin]; Aldosterona [INN-Spanish]; [3H]aldosterone; 18-Aldocorticosterone; Aldosterone [INN:BAN:DCF]; 11beta,21-Dihydroxypregn-4-ene-3,18,20-trione; 11beta,21-Dihydroxy-3,20-diketo-4-pregnen-18-al; 11beta,21-Dihydroxy-3,20-diketopregn-4-ene-18-al; NSC 73856; 18-Formyl-11beta,21-dihydroxy-4-pregnene-3,20-dione; UNII-4964P6T9RB; Aldocorten; D-Aldosterone; Aldosterone, (11 beta,17 alpha)-Isomer; Aldosterone, (+-)-Isomer; (11BETA)-11,21-DIHYDROXY-3,20-DIOXOPREGN-4-EN-18-AL; (8S,9S,10R,11S,13R,14S,17S)-11-hydroxy-17-(2-hydroxyacetyl)-10-methyl-3-oxo-1,2,6,7,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthrene-13-carbaldehyde; 11beta,21-Dihydroxy-3,20-dioxo-4-pregnen-18-al; 11beta,21-Dihydroxy-3,20-dioxo-4-pregnen-18-al, 18,11-halbacetal; 11beta,21-dihydroxy-3,20-dioxo-pregn-4-ene-18-al; 11beta,21-dihydroxy-3,20-dioxopregn-4-en-18-al
Indication
Disease Entry ICD 11 Status REF
Hypertension BA00-BA04 Approved [1], [2]
Therapeutic Class
Antihypertensive Agents
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 0 Molecular Weight (mw) 360.4
Topological Polar Surface Area (xlogp) 1.1
Rotatable Bond Count (rotbonds) 3
Hydrogen Bond Donor Count (hbonddonor) 2
Hydrogen Bond Acceptor Count (hbondacc) 5
Chemical Identifiers
Formula
C21H28O5
IUPAC Name
(8S,9S,10R,11S,13R,14S,17S)-11-hydroxy-17-(2-hydroxyacetyl)-10-methyl-3-oxo-1,2,6,7,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthrene-13-carbaldehyde
Canonical SMILES
C[C@]12CCC(=O)C=C1CC[C@@H]3[C@@H]2[C@H](C[C@]4([C@H]3CC[C@@H]4C(=O)CO)C=O)O
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
InChIKey
PQSUYGKTWSAVDQ-ZVIOFETBSA-N
Cross-matching ID
PubChem CID
5839
ChEBI ID
CHEBI:27584
CAS Number
52-39-1
DrugBank ID
DB04630
TTD ID
D0I1LH
VARIDT ID
DR00629
INTEDE ID
DR0057

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Mineralocorticoid receptor (MR) TT26PHO MCR_HUMAN Agonist [3]
Solute carrier family 12 member 1 (SLC12A1) TTS087L S12A1_HUMAN Blocker [4], [5]

Drug Transporter (DTP)
DTP Name DTP ID UniProt ID MOA REF
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [6]

Drug-Metabolizing Enzyme (DME)
DME Name DME ID UniProt ID MOA REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Substrate [7]
Cytochrome P450 3A5 (CYP3A5) DEIBDNY CP3A5_HUMAN Substrate [8]
UDP-glucuronosyltransferase 2B7 (UGT2B7) DEB3CV1 UD2B7_HUMAN Substrate [9]
Steroid 11-beta-hydroxylase (CYP11B1) DEPE0RD C11B1_HUMAN Substrate [10]
Aldosterone synthase (CYP11B2) DE6TYUK C11B2_HUMAN Substrate [11]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease Hypertension
ICD Disease Classification BA00-BA04
Molecule Name Molecule Type Gene Name p-value Fold-Change Z-score
Mineralocorticoid receptor (MR) DTT NR3C2 7.31E-01 -5.31E-04 -1.53E-03
P-glycoprotein 1 (ABCB1) DTP P-GP 2.30E-01 3.06E-01 7.43E-01
Steroid 11-beta-hydroxylase (CYP11B1) DME CYP11B1 2.70E-01 9.19E-02 9.75E-01
Cytochrome P450 3A5 (CYP3A5) DME CYP3A5 8.58E-01 -3.73E-03 -1.00E-02
Aldosterone synthase (CYP11B2) DME CYP11B2 1.08E-01 -2.14E-01 -1.14E+00
Cytochrome P450 3A4 (CYP3A4) DME CYP3A4 2.76E-01 -4.64E-01 -9.16E-01
Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This Drug

References

1 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 2872).
2 Treatment of hypertension with olmesartan medoxomil, alone and in combination with a diuretic: an update. J Hum Hypertens. 2007 Sep;21(9):699-708.
3 Stimulation of testosterone production in rat Leydig cells by aldosterone is mineralocorticoid receptor mediated. Mol Cell Endocrinol. 2005 Nov 24;243(1-2):35-42.
4 Nongenomic effect of aldosterone on ion transport pathways of red blood cells. Cell Physiol Biochem. 2008;22(1-4):269-78.
5 Aldosterone regulates the Na-K-2Cl cotransporter in vascular smooth muscle. Hypertension. 2003 May;41(5):1131-5.
6 MDR1 genotype-dependent regulation of the aldosterone system in humans. Pharmacogenet Genomics. 2007 Feb;17(2):137-44.
7 Aldosterone receptor antagonists: effective but often forgotten. Circulation. 2010 Feb 23;121(7):934-9.
8 CYP3A5 genotype is associated with elevated blood pressure. Pharmacogenet Genomics. 2005 Oct;15(10):737-41.
9 Human uridine diphosphate-glucuronosyltransferase UGT2B7 conjugates mineralocorticoid and glucocorticoid metabolites. Endocrinology. 2003 Jun;144(6):2659-68.
10 Quantitative assessment of CYP11B1 and CYP11B2 expression in aldosterone-producing adenomas. Eur J Endocrinol. 2002 Dec;147(6):795-802.
11 Heteroaryl-substituted naphthalenes and structurally modified derivatives: selective inhibitors of CYP11B2 for the treatment of congestive heart failure and myocardial fibrosis. J Med Chem. 2005 Oct 20;48(21):6632-42.
12 Expression levels and activation of a PXR variant are directly related to drug resistance in osteosarcoma cell lines. Cancer. 2007 Mar 1;109(5):957-65.
13 Contribution of human hepatic cytochrome P450 isoforms to regioselective hydroxylation of steroid hormones. Xenobiotica. 1998 Jun;28(6):539-47.
14 Comprehensive evaluation of tamoxifen sequential biotransformation by the human cytochrome P450 system in vitro: prominent roles for CYP3A and CYP2D6. J Pharmacol Exp Ther. 2004 Sep;310(3):1062-75.
15 Isoform-specific regulation of cytochromes P450 expression by estradiol and progesterone. Drug Metab Dispos. 2013 Feb;41(2):263-9.
16 Metabolic interactions between acetaminophen (paracetamol) and two flavonoids, luteolin and quercetin, through in-vitro inhibition studies. J Pharm Pharmacol. 2017 Dec;69(12):1762-1772.
17 Potent mechanism-based inhibition of CYP3A4 by imatinib explains its liability to interact with CYP3A4 substrates. Br J Pharmacol. 2012 Apr;165(8):2787-98.
18 Effects of morin on the pharmacokinetics of etoposide in rats. Biopharm Drug Dispos. 2007 Apr;28(3):151-6.
19 The metabolism of zidovudine by human liver microsomes in vitro: formation of 3'-amino-3'-deoxythymidine. Biochem Pharmacol. 1994 Jul 19;48(2):267-76.
20 Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675.
21 Drug related genetic polymorphisms affecting adverse reactions to methotrexate, vinblastine, doxorubicin and cisplatin in patients with urothelial cancer. J Urol. 2008 Dec;180(6):2389-95.
22 Human prostate CYP3A5: identification of a unique 5'-untranslated sequence and characterization of purified recombinant protein. Biochem Biophys Res Commun. 1999 Jul 14;260(3):676-81.
23 Polymorphisms in cytochrome P4503A5 (CYP3A5) may be associated with race and tumor characteristics, but not metabolism and side effects of tamoxifen in breast cancer patients. Cancer Lett. 2005 Jan 10;217(1):61-72.
24 Drug Interactions Flockhart Table
25 Induction of hepatic CYP2E1 by a subtoxic dose of acetaminophen in rats: increase in dichloromethane metabolism and carboxyhemoglobin elevation. Drug Metab Dispos. 2007 Oct;35(10):1754-8.
26 Urinary 6 beta-hydroxycortisol excretion in rheumatoid arthritis. Br J Rheumatol. 1997 Jan;36(1):54-8.
27 Clinical pharmacokinetics of imatinib. Clin Pharmacokinet. 2005;44(9):879-94.
28 Kinetics and regulation of cytochrome P450-mediated etoposide metabolism. Drug Metab Dispos. 2004 Sep;32(9):993-1000.
29 Differential mechanism-based inhibition of CYP3A4 and CYP3A5 by verapamil. Drug Metab Dispos. 2005 May;33(5):664-71.
30 Studies on the origin of circulating 18-hydroxycortisol and 18-oxocortisol in normal human subjects. J Clin Endocrinol Metab. 2004 Sep;89(9):4628-33.
31 Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448.
32 Functional expression of human mitochondrial CYP11B2 in fission yeast and identification of a new internal electron transfer protein, etp1. Biochemistry. 2002 Feb 19;41(7):2311-21.
33 Metabolism and transport of tamoxifen in relation to its effectiveness: new perspectives on an ongoing controversy. Future Oncol. 2014 Jan;10(1):107-22.
34 Determination of UDP-glucuronosyltransferase UGT2B7 activity in human liver microsomes by ultra-performance liquid chromatography with MS detection. J Chromatogr B Analyt Technol Biomed Life Sci. 2008 Jul 1;870(1):84-90.
35 Pharmacokinetic and pharmacodynamic interaction of lorazepam and valproic acid in relation to UGT2B7 genetic polymorphism in healthy subjects. Clin Pharmacol Ther. 2008 Apr;83(4):595-600.
36 PharmGKB summary: mycophenolic acid pathway. Pharmacogenet Genomics. 2014 Jan;24(1):73-9.
37 Pitavastatin: a review in hypercholesterolemia. Am J Cardiovasc Drugs. 2017 Apr;17(2):157-168.
38 Troglitazone glucuronidation in human liver and intestine microsomes: high catalytic activity of UGT1A8 and UGT1A10. Drug Metab Dispos. 2002 Dec;30(12):1462-9.
39 Ezetimibe: a review of its metabolism, pharmacokinetics and drug interactions. Clin Pharmacokinet. 2005;44(5):467-94.
40 Pharmacogenomics of statins: understanding susceptibility to adverse effects. Pharmgenomics Pers Med. 2016 Oct 3;9:97-106.
41 Human intestinal transporter database: QSAR modeling and virtual profiling of drug uptake, efflux and interactions. Pharm Res. 2013 Apr;30(4):996-1007.
42 MDR1 (ABCB1) G1199A (Ser400Asn) polymorphism alters transepithelial permeability and sensitivity to anticancer agents. Cancer Chemother Pharmacol. 2009 Jun;64(1):183-8.
43 Mammalian drug efflux transporters of the ATP binding cassette (ABC) family in multidrug resistance: A review of the past decade. Cancer Lett. 2016 Jan 1;370(1):153-64.
44 Folate transporter expression decreases in the human placenta throughout pregnancy and in pre-eclampsia. Pregnancy Hypertens. 2012 Apr;2(2):123-31.
45 Comparative studies on in vitro methods for evaluating in vivo function of MDR1 P-glycoprotein. Pharm Res. 2001 Dec;18(12):1660-8.
46 Antiestrogens and steroid hormones: substrates of the human P-glycoprotein. Biochem Pharmacol. 1994 Jul 19;48(2):287-92.
47 Association of genetic polymorphisms in the influx transporter SLCO1B3 and the efflux transporter ABCB1 with imatinib pharmacokinetics in patients with chronic myeloid leukemia. Ther Drug Monit. 2011 Apr;33(2):244-50.
48 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
49 Mineralocorticoid receptor-mediated inhibition of the hypothalamic-pituitary-adrenal axis in aged humans. J Gerontol A Biol Sci Med Sci. 2003 Oct;58(10):B900-5.
50 Characterization of rat brain aldosterone receptors reveals high affinity for corticosterone. Endocrinology. 1983 Dec;113(6):2043-51.
51 Biochemical mechanisms of New Molecular Entities (NMEs) approved by United States FDA during 2001-2004: mechanisms leading to optimal efficacy and ... Curr Top Med Chem. 2006;6(5):461-78.
52 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
53 ZK91587: a novel synthetic antimineralocorticoid displays high affinity for corticosterone (type I) receptors in the rat hippocampus. Life Sci. 1988;43(19):1537-43.
54 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 626).
55 Nonsteroidal antagonists of the mineralocorticoid receptor. Curr Opin Nephrol Hypertens. 2015 Sep;24(5):417-24.
56 Update of diuretics in the treatment of hypertension. Am J Ther. 2007 Mar-Apr;14(2):154-60.
57 Nerve Terminal GABAA Receptors Activate Ca2+/Calmodulin-dependent Signaling to Inhibit Voltage-gated Ca2+ Influx and Glutamate Release. J Biol Chem. 2009 Mar 27;284(13):8726-37.
58 Na-K-Cl cotransport regulates intracellular volume and monolayer permeability of trabecular meshwork cells. Am J Physiol. 1995 Apr;268(4 Pt 1):C1067-74.
59 Genetic variation in the renal sodium transporters NKCC2, NCC, and ENaC in relation to the effects of loop diuretic drugs. Clin Pharmacol Ther. 2007 Sep;82(3):300-9.
60 DrugBank: a knowledgebase for drugs, drug actions and drug targets. Nucleic Acids Res. 2008 Jan;36(Database issue):D901-6.
61 Function and regulation of epithelial sodium transporters in the kidney of a salt-sensitive hypertensive rat model. J Hypertens. 2007 May;25(5):1065-72.
62 The 45-year story of the development of an anti-aldosterone more specific than spironolactone. Mol Cell Endocrinol. 2004 Mar 31;217(1-2):45-52.