Identification

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Name
Fludrocortisone
Accession Number
DB00687  (APRD00756, DB02478)
Type
Small Molecule
Groups
Approved, Investigational
Description

Fludrocortisone is a synthetic mineralocorticoid used in conjunction with hydrocortisone to replace missing endogenous corticosteroids in patients with adrenal insufficiency.9,11 It is functionally similar to aldosterone, the body's primary endogenous mineralocorticoid, and is structurally analogous to cortisol, differing only by a fluorine atom at the 9-position of the steroid structure - this fluorination is thought to be crucial to fludrocortisone's significant mineralocorticoid potency.7

Structure
Thumb
Synonyms
  • 9alpha-Fluorocortisol
  • Fludrocortison
  • Fludrocortisona
  • Fludrocortisone
  • Fludrocortisonum
  • Fluohydrocortisone
External IDs
StC 1400 / U 5963
Product Ingredients
IngredientUNIICASInChI Key
Fludrocortisone acetateV47IF0PVH4514-36-3SYWHXTATXSMDSB-GSLJADNHSA-N
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
FlorinefTabletOralPaladin Labs Inc1995-12-31Not applicableCanada
Florinef AcetateTablet.1 mg/1OralMonarch Pharmaceuticals, Inc.1955-08-182007-09-20Us
Florinef AcetateTablet0.1 mg/1OralPhysicians Total Care, Inc.1993-11-022011-05-31Us
Florinef Acetate 0.1mgTabletOralSquibb Canada Inc., Division Of Bristol Myers Squibb Canada Inc.1958-12-311997-08-14Canada
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Fludrocortisone AcetateTablet0.1 mg/1OralWest Ward Pharmaceutical2011-07-22Not applicableUs
Fludrocortisone AcetateTablet0.1 mg/1OralAmerican Health Packaging2008-09-09Not applicableUs
Fludrocortisone AcetateTablet0.1 mg/1OralAv Kare, Inc.2009-10-20Not applicableUs
Fludrocortisone AcetateTablet0.1 mg/1OralPhysicians Total Care, Inc.2005-10-06Not applicableUs54868 544620180906 25352 v6ed2v
Fludrocortisone AcetateTablet0.1 mg/1OralTeva Pharmaceuticals USA, Inc.2003-02-14Not applicableUs00555 0997 02 nlmimage10 b107d88e
Fludrocortisone AcetateTablet0.1 mg/1OralAv Pak2011-08-01Not applicableUs
Fludrocortisone AcetateTablet0.1 mg/1OralPD-Rx Pharmaceuticals, Inc.2003-02-14Not applicableUs
Fludrocortisone AcetateTablet0.1 mg/1OralRemedy Repack2011-10-032012-10-03Us
Fludrocortisone AcetateTablet0.1 mg/1Oralbryant ranch prepack2002-03-18Not applicableUs
Fludrocortisone AcetateTablet0.1 mg/1OralNcs Health Care Of Ky, Inc Dba Vangard Labs2002-03-30Not applicableUs
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Unapproved/Other Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
Florinef AcetateFludrocortisone acetate (0.1 mg/1)TabletOralPhysicians Total Care, Inc.1993-11-022011-05-31Us
International/Other Brands
Adixone (Genopharm) / Astonin (Merck) / Cortineff (Polfa Pabianice) / Florinef Acetaat (Bristol-Myers Squibb) / Florinefe (Bristol-Myers Squibb) / Fludrocortison (Bristol-Myers Squibb) / Lonikan (Merck)
Categories
UNII
U0476M545B
CAS number
127-31-1
Weight
Average: 380.4504
Monoisotopic: 380.199902243
Chemical Formula
C21H29FO5
InChI Key
AAXVEMMRQDVLJB-BULBTXNYSA-N
InChI
InChI=1S/C21H29FO5/c1-18-7-5-13(24)9-12(18)3-4-15-14-6-8-20(27,17(26)11-23)19(14,2)10-16(25)21(15,18)22/h9,14-16,23,25,27H,3-8,10-11H2,1-2H3/t14-,15-,16-,18-,19-,20-,21-/m0/s1
IUPAC Name
(1R,3aS,3bS,9aS,9bR,10S,11aS)-9b-fluoro-1,10-dihydroxy-1-(2-hydroxyacetyl)-9a,11a-dimethyl-1H,2H,3H,3aH,3bH,4H,5H,7H,8H,9H,9aH,9bH,10H,11H,11aH-cyclopenta[a]phenanthren-7-one
SMILES
[H][C@@]12CC[C@](O)(C(=O)CO)[C@@]1(C)C[C@H](O)[C@@]1(F)[C@@]2([H])CCC2=CC(=O)CC[C@]12C

Pharmacology

Indication

Fludrocortisone is indicated as partial replacement therapy for primary or secondary adrenocortical insufficiency in Addison's disease. It is also indicated for the treatment of salt-losing androgenital syndrome.14

Associated Conditions
Pharmacodynamics

Fludrocortisone is a synthetic mineralocorticoid used to replace endogenous aldosterone in conditions resulting in missing or inadequate endogenous synthesis.14,15 It acts on the kidneys to increase both sodium reabsorption and potassium excretion.13,11 As its effects are exerted at the transcriptional level, a single dose of fludrocortisone may work over the course of 1-2 days15 despite a relatively short plasma half-life.6,9,10 Like other systemic corticosteroids, fludrocortisone may mask signs of infection by depressing the normal immune response - infections occurring during fludrocortisone therapy should be promptly treated with appropriate antimicrobial therapy.14

Mechanism of action

The main endogenous mineralocorticoid, aldosterone, is produced in the zona glomerulosa of the adrenal cortex - it acts on mineralocorticoid receptors in the kidneys to increase sodium reabsorption and potassium excretion, which in turn helps to regulate plasma electrolyte composition and blood pressure.13 In conditions of adrenal insufficiency, such as Addison’s disease, aldosterone is not produced (or is produced in insufficient quantities) and must be replaced by exogenous mineralocorticoids such as fludrocortisone.11

Fludrocortisone binding to mineralocorticoid receptors causes alterations to DNA transcription and translation of proteins that result in an increased density of sodium channels on the apical side of renal tubule cells and an increased density of Na+-K+-ATPase on the basolateral side.13 These increases in receptor density result in increased plasma sodium concentrations, and thus increased blood pressure, as well as a decreased plasma potassium concentration. Fludrocortisone may also exert a direct effect on plasma sodium levels via action at the Na+-H+ exchanger found in the apical membrane of renal tubule cells.13

Fludrocortisone also acts on glucocorticoid receptors, albeit with a much lower affinity - the glucocorticoid potency of fludrocortisone is approximately 5-10 times that of endogenous cortisol, whereas its mineralocorticoid potency is 200-400 times greater.7

TargetActionsOrganism
AMineralocorticoid receptor
agonist
Humans
UGlucocorticoid receptor
agonist
Humans
Additional Data Available
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Contraindications

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Blackbox Warnings

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Absorption

Absorption of fludrocortisone following oral administration is rapid and complete.16,9,10,6 Pharmacokinetic studies have estimated the Cmax to be 0.0012 to 0.20 μg/L with a Tmax between 0.5 and 2 hours.9,10 The AUC0-∞ of fludrocortisone after oral administration has been variably estimated to be between 1.22 to 3.07 μg.h/L.9,10

Volume of distribution

The apparent volume of distribution of fludrocortisone is 80-85 L.9,6 Distribution into CSF appears minimal - the observed ratio of CSF drug concentration versus plasma drug concentration is 1:6.16

Protein binding

Fludrocortisone is 70-80% protein bound in plasma, mostly to albumin and corticosteroid-binding globulin.16,10

Metabolism

There exists is a paucity of information regarding the specific metabolic pathway in vivo of fludrocortisone. The 9α-fluorination of fludrocortisone appears to greatly simplify its metabolism as compared to other corticosteroids8 - while oxidation via 11-hydroxysteroid dehydrogenases has been observed,3 this reaction is greatly impaired as the fluorine moiety appears to confer "protection" from 11β-oxidation by these enzymes. The reduction in 11β-oxidation is thought to be one of the reasons behind fludrocortisone's profound mineralocorticoid potency.7 An in vitro study generated only two metabolites following incubation in human liver microsomes and cytosol, namely 20β-dihydrofluorocortisol and 6β-hydroxyfluorocortisol, and did not explore in detail the potential enzymes responsible for this reaction.8

Given that fludrocortisone is a corticosteroid, a class of medications known to be metabolized by the CYP3A family,12 and is not recommended to be given with strong inhibitors/inducers of CYP3A,15 it is likely that the CYP3A family of enzymes contributes in some way to its metabolism (though this information does not appear to have been specifically elucidated for fludrocortisone).

Route of elimination

Approximately 80% of an administered dose of fludrocortisone shows up in the urine, with the other 20% likely eliminated via fecal or biliary route.16,10

Half life

The plasma half-life of fludrocortisone has been variably reported to be between 1-3.5 hours,6,9,10 though prescribing information gives an approximate half-life of 18-36 hours.15

Clearance

Population pharmacokinetics have estimated the plasma clearance of fludrocortisone to be 40.8 L/h.9

Toxicity

The oral LD50 of fludrocortisone in rats is >1g/kg.17 Acute overdosage of fludrocortisone is likely to result in symptoms consistent with its adverse effect profile. Patients receiving a single large dose should be treated with plenty of water by mouth and should undergo monitoring of serum electrolytes, particularly potassium and sodium, and be treated appropriately for any developing imbalances.15,16

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
(R)-warfarinFludrocortisone may increase the anticoagulant activities of (R)-warfarin.
(S)-WarfarinFludrocortisone may increase the anticoagulant activities of (S)-Warfarin.
1-TestosteroneThe risk or severity of edema formation can be increased when 1-Testosterone is combined with Fludrocortisone.
1,10-PhenanthrolineThe therapeutic efficacy of 1,10-Phenanthroline can be decreased when used in combination with Fludrocortisone.
16-BromoepiandrosteroneThe risk or severity of edema formation can be increased when 16-Bromoepiandrosterone is combined with Fludrocortisone.
19-norandrostenedioneThe risk or severity of edema formation can be increased when 19-norandrostenedione is combined with Fludrocortisone.
1alpha-Hydroxyvitamin D5The therapeutic efficacy of 1alpha-Hydroxyvitamin D5 can be decreased when used in combination with Fludrocortisone.
1alpha,24S-Dihydroxyvitamin D2The therapeutic efficacy of 1alpha,24S-Dihydroxyvitamin D2 can be decreased when used in combination with Fludrocortisone.
2-MethoxyethanolThe risk or severity of adverse effects can be increased when Fludrocortisone is combined with 2-Methoxyethanol.
2,4-thiazolidinedioneThe risk or severity of hyperglycemia can be increased when Fludrocortisone is combined with 2,4-thiazolidinedione.
Additional Data Available
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    Extended Description

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    Severity

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    Action

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Food Interactions
  • Avoid excess salt/sodium unless otherwise instructed by your physician.
  • Take with food to reduce irritation.

References

Synthesis Reference

U.S. Patent 2,957,013

General References
  1. Agarwal MK, Coupry F, Philippe M: Physiological activity and receptor binding of 9 alpha fluorohydrocortisone. Biochem Biophys Res Commun. 1977 Sep 23;78(2):747-53. doi: 10.1016/0006-291x(77)90242-x. [PubMed:907708]
  2. Lan NC, Graham B, Bartter FC, Baxter JD: Binding of steroids to mineralocorticoid receptors: implications for in vivo occupancy by glucocorticoids. J Clin Endocrinol Metab. 1982 Feb;54(2):332-42. doi: 10.1210/jcem-54-2-332. [PubMed:6274900]
  3. Diederich S, Eigendorff E, Burkhardt P, Quinkler M, Bumke-Vogt C, Rochel M, Seidelmann D, Esperling P, Oelkers W, Bahr V: 11beta-hydroxysteroid dehydrogenase types 1 and 2: an important pharmacokinetic determinant for the activity of synthetic mineralo- and glucocorticoids. J Clin Endocrinol Metab. 2002 Dec;87(12):5695-701. doi: 10.1210/jc.2002-020970. [PubMed:12466373]
  4. Abboud R, Akil M, Charcosset C, Greige-Gerges H: Interaction of glucocorticoids and progesterone derivatives with human serum albumin. Chem Phys Lipids. 2017 Oct;207(Pt B):271-278. doi: 10.1016/j.chemphyslip.2017.04.007. Epub 2017 Apr 21. [PubMed:28435101]
  5. SANDBERG AA, SLAUNWHITE WR Jr, CARTER AC: Transcortin: a corticosteroid-binding protein of plasma. III. The effects of various steroids. J Clin Invest. 1960 Dec;39:1914-26. doi: 10.1172/JCI104216. [PubMed:13746120]
  6. Mitsky VP, Workman RJ, Nicholson WE, Vernikos J, Robertson RM, Robertson D: A sensitive radioimmunoassay for fludrocortisone in human plasma. Steroids. 1994 Sep;59(9):555-8. doi: 10.1016/0039-128x(94)90074-4. [PubMed:7846738]
  7. Oelkers W, Buchen S, Diederich S, Krain J, Muhme S, Schoneshofer M: Impaired renal 11 beta-oxidation of 9 alpha-fluorocortisol: an explanation for its mineralocorticoid potency. J Clin Endocrinol Metab. 1994 Apr;78(4):928-32. [PubMed:8157723]
  8. Abel SM, Back DJ, Maggs JL, Park BK: Cortisol metabolism by human liver in vitro--IV. Metabolism of 9 alpha-fluorocortisol by human liver microsomes and cytosol. J Steroid Biochem Mol Biol. 1993 Dec;46(6):833-9. doi: 10.1016/0960-0760(93)90326-r. [PubMed:8274419]
  9. Hamitouche N, Comets E, Ribot M, Alvarez JC, Bellissant E, Laviolle B: Population Pharmacokinetic-Pharmacodynamic Model of Oral Fludrocortisone and Intravenous Hydrocortisone in Healthy Volunteers. AAPS J. 2017 May;19(3):727-735. doi: 10.1208/s12248-016-0041-9. Epub 2017 Jan 12. [PubMed:28083797]
  10. Banda J, Lakshmanan R, Vvs SP, Gudla SP, Prudhivi R: A highly sensitive method for the quantification of fludrocortisone in human plasma using ultra-high-performance liquid chromatography tandem mass spectrometry and its pharmacokinetic application. Biomed Chromatogr. 2015 Aug;29(8):1213-9. doi: 10.1002/bmc.3410. Epub 2015 Jan 22. [PubMed:25611194]
  11. Charmandari E, Nicolaides NC, Chrousos GP: Adrenal insufficiency. Lancet. 2014 Jun 21;383(9935):2152-67. doi: 10.1016/S0140-6736(13)61684-0. Epub 2014 Feb 4. [PubMed:24503135]
  12. Rendic S: Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448. [PubMed:11996015]
  13. 32. (2012). In Rang and Dale's Pharmacology (7th ed.). Edinburgh: Elsevier/Churchill Livingstone. [ISBN:978-0-7020-3471-8]
  14. DPD Approved Drugs: Florinef [Link]
  15. MedSafe NZ: Florinef [Link]
  16. UK Approved Drugs: Fludrocortisone [Link]
  17. CaymanChem: Fludrocortisone acetate MSDS [Link]
External Links
Human Metabolome Database
HMDB0014825
KEGG Drug
D07967
KEGG Compound
C07004
PubChem Compound
31378
PubChem Substance
46508616
ChemSpider
29111
ChEBI
50885
ChEMBL
CHEMBL1201388
Therapeutic Targets Database
DAP001105
PharmGKB
PA164743961
Guide to Pharmacology
GtP Drug Page
HET
ZK5
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Fludrocortisone
ATC Codes
S02CA07 — Fludrocortisone and antiinfectivesS01CA06 — Fludrocortisone and antiinfectivesH02AA02 — FludrocortisoneS03CA05 — Fludrocortisone and antiinfectives
AHFS Codes
  • 68:04.00 — Adrenals
PDB Entries
1gs4

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0TerminatedTreatmentHearing Loss, Sensorineural1
1CompletedBasic ScienceHealthy Volunteers / Pharmacodynamics1
1CompletedTreatmentDepression1
1CompletedTreatmentMultiple System Atrophy (MSA) / Orthostatic Hypotension / Parkinson's Disease (PD)1
1RecruitingOtherHealthy Volunteers1
1, 2TerminatedBasic ScienceRenin Angiotensin1
2Active Not RecruitingTreatmentAutonomic Disturbances in Parkinson's Disease1
2CompletedBasic ScienceHealthy Volunteers1
2CompletedTreatmentMelanoma1
2Not Yet RecruitingTreatmentCongenital Adrenal Hyperplasia (CAH)1
2Not Yet RecruitingTreatmentShock, Septic1
2RecruitingTreatmentPartial Mineralocorticoid Deficiency1
3CompletedTreatmentAdrenal Insufficiency / Pneumonia / Traumas / Traumatic Brain Injury (TBI)1
3CompletedTreatmentShock, Septic2
3RecruitingTreatmentShock, Cardiogenic1
3WithdrawnTreatmentShock, Septic1
4CompletedTreatmentSyncope, Vasovagal, Neurally-Mediated1
4Not Yet RecruitingTreatmentNeurogenic Orthostatic Hypotension1
4Unknown StatusDiagnosticHigh Blood Pressure (Hypertension)1
4WithdrawnTreatmentAdrenal Insufficiency / Sepsis1
Not AvailableCompletedNot AvailableAcidosis, Renal Tubular / Calcium Nephrolithiasis / Vacuolar Proton-Translocating ATPases1
Not AvailableCompletedTreatmentMajor Depressive Disorder (MDD)1
Not AvailableCompletedTreatmentOrthostatic Hypotension1
Not AvailableRecruitingBasic ScienceMajor Depressive Disorder (MDD)1
Not AvailableWithdrawnNot AvailableType 1 Insulin-Dependent Diabetes Mellitus1

Pharmacoeconomics

Manufacturers
  • King pharmaceuticals inc
  • Barr laboratories inc
  • Impax laboratories inc
Packagers
  • Amerisource Health Services Corp.
  • Avkare Incorporated
  • Barr Pharmaceuticals
  • Bristol-Myers Squibb Co.
  • Cardinal Health
  • E.R. Squibb and Sons LLC
  • Global Pharmaceuticals
  • Heartland Repack Services LLC
  • Impax Laboratories Inc.
  • Kaiser Foundation Hospital
  • Medisca Inc.
  • Physicians Total Care Inc.
  • Resource Optimization and Innovation LLC
  • Vangard Labs Inc.
Dosage forms
FormRouteStrength
TabletOral
TabletOral.1 mg/1
TabletOral0.1 mg/1
Prices
Unit descriptionCostUnit
Fludrocortisone acetate powder73.14USD g
Florinef acetate 0.1 mg tablet1.49USD tablet
Fludrocortisone Acetate 0.1 mg tablet0.81USD tablet
Fludrocortisone 0.1 mg tablet0.75USD tablet
Florinef 0.1 mg Tablet0.25USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.224 mg/mLALOGPS
logP1.35ALOGPS
logP1.32ChemAxon
logS-3.2ALOGPS
pKa (Strongest Acidic)12.55ChemAxon
pKa (Strongest Basic)-3.3ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area94.83 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity96.93 m3·mol-1ChemAxon
Polarizability39.53 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9927
Blood Brain Barrier+0.9731
Caco-2 permeable+0.8415
P-glycoprotein substrateSubstrate0.7911
P-glycoprotein inhibitor INon-inhibitor0.8385
P-glycoprotein inhibitor IINon-inhibitor0.9351
Renal organic cation transporterNon-inhibitor0.7774
CYP450 2C9 substrateNon-substrate0.8799
CYP450 2D6 substrateNon-substrate0.909
CYP450 3A4 substrateSubstrate0.7138
CYP450 1A2 substrateNon-inhibitor0.9306
CYP450 2C9 inhibitorNon-inhibitor0.9023
CYP450 2D6 inhibitorNon-inhibitor0.9201
CYP450 2C19 inhibitorNon-inhibitor0.9285
CYP450 3A4 inhibitorNon-inhibitor0.8772
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.903
Ames testNon AMES toxic0.8895
CarcinogenicityNon-carcinogens0.9479
BiodegradationNot ready biodegradable0.9964
Rat acute toxicity2.1686 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9591
hERG inhibition (predictor II)Inhibitor0.5213
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as 21-hydroxysteroids. These are steroids carrying a hydroxyl group at the 21-position of the steroid backbone.
Kingdom
Organic compounds
Super Class
Lipids and lipid-like molecules
Class
Steroids and steroid derivatives
Sub Class
Hydroxysteroids
Direct Parent
21-hydroxysteroids
Alternative Parents
Gluco/mineralocorticoids, progestogins and derivatives / 20-oxosteroids / 11-beta-hydroxysteroids / 17-hydroxysteroids / 3-oxo delta-4-steroids / Halogenated steroids / Delta-4-steroids / Cyclohexenones / Tertiary alcohols / Alpha-hydroxy ketones
show 8 more
Substituents
Progestogin-skeleton / 21-hydroxysteroid / Pregnane-skeleton / 20-oxosteroid / 3-oxo-delta-4-steroid / 3-oxosteroid / 17-hydroxysteroid / 11-hydroxysteroid / 11-beta-hydroxysteroid / 9-halo-steroid
show 24 more
Molecular Framework
Aliphatic homopolycyclic compounds
External Descriptors
11beta-hydroxy steroid, 17alpha-hydroxy steroid, 3-oxo Delta(4)-steroid, 20-oxo steroid, fluorinated steroid, mineralocorticoid, 21-hydroxy steroid, C21-steroid (CHEBI:50885) / C21 steroids (gluco/mineralocorticoids, progestogens) and derivatives (C07004) / C21 steroids (gluco/mineralocorticoids, progestogins) and derivatives (LMST02030103)

Targets

Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Agonist
General Function
Zinc ion binding
Specific Function
Receptor for both mineralocorticoids (MC) such as aldosterone and glucocorticoids (GC) such as corticosterone or cortisol. Binds to mineralocorticoid response elements (MRE) and transactivates targ...
Gene Name
NR3C2
Uniprot ID
P08235
Uniprot Name
Mineralocorticoid receptor
Molecular Weight
107066.575 Da
References
  1. Agarwal MK, Coupry F, Philippe M: Physiological activity and receptor binding of 9 alpha fluorohydrocortisone. Biochem Biophys Res Commun. 1977 Sep 23;78(2):747-53. doi: 10.1016/0006-291x(77)90242-x. [PubMed:907708]
  2. Lan NC, Graham B, Bartter FC, Baxter JD: Binding of steroids to mineralocorticoid receptors: implications for in vivo occupancy by glucocorticoids. J Clin Endocrinol Metab. 1982 Feb;54(2):332-42. doi: 10.1210/jcem-54-2-332. [PubMed:6274900]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Agonist
General Function
Zinc ion binding
Specific Function
Receptor for glucocorticoids (GC). Has a dual mode of action: as a transcription factor that binds to glucocorticoid response elements (GRE), both for nuclear and mitochondrial DNA, and as a modula...
Gene Name
NR3C1
Uniprot ID
P04150
Uniprot Name
Glucocorticoid receptor
Molecular Weight
85658.57 Da
References
  1. Agarwal MK, Coupry F, Philippe M: Physiological activity and receptor binding of 9 alpha fluorohydrocortisone. Biochem Biophys Res Commun. 1977 Sep 23;78(2):747-53. doi: 10.1016/0006-291x(77)90242-x. [PubMed:907708]
  2. Lan NC, Graham B, Bartter FC, Baxter JD: Binding of steroids to mineralocorticoid receptors: implications for in vivo occupancy by glucocorticoids. J Clin Endocrinol Metab. 1982 Feb;54(2):332-42. doi: 10.1210/jcem-54-2-332. [PubMed:6274900]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Rendic S: Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448. [PubMed:11996015]
  2. Vienna presentation 2012 [File]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid binding
Specific Function
Catalyzes the conversion of cortisol to the inactive metabolite cortisone. Modulates intracellular glucocorticoid levels, thus protecting the nonselective mineralocorticoid receptor from occupation...
Gene Name
HSD11B2
Uniprot ID
P80365
Uniprot Name
Corticosteroid 11-beta-dehydrogenase isozyme 2
Molecular Weight
44126.06 Da
References
  1. Diederich S, Eigendorff E, Burkhardt P, Quinkler M, Bumke-Vogt C, Rochel M, Seidelmann D, Esperling P, Oelkers W, Bahr V: 11beta-hydroxysteroid dehydrogenase types 1 and 2: an important pharmacokinetic determinant for the activity of synthetic mineralo- and glucocorticoids. J Clin Endocrinol Metab. 2002 Dec;87(12):5695-701. doi: 10.1210/jc.2002-020970. [PubMed:12466373]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
11-beta-hydroxysteroid dehydrogenase [nad(p)] activity
Specific Function
Catalyzes reversibly the conversion of cortisol to the inactive metabolite cortisone. Catalyzes reversibly the conversion of 7-ketocholesterol to 7-beta-hydroxycholesterol. In intact cells, the rea...
Gene Name
HSD11B1
Uniprot ID
P28845
Uniprot Name
Corticosteroid 11-beta-dehydrogenase isozyme 1
Molecular Weight
32400.665 Da
References
  1. Diederich S, Eigendorff E, Burkhardt P, Quinkler M, Bumke-Vogt C, Rochel M, Seidelmann D, Esperling P, Oelkers W, Bahr V: 11beta-hydroxysteroid dehydrogenase types 1 and 2: an important pharmacokinetic determinant for the activity of synthetic mineralo- and glucocorticoids. J Clin Endocrinol Metab. 2002 Dec;87(12):5695-701. doi: 10.1210/jc.2002-020970. [PubMed:12466373]

Carriers

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Toxic substance binding
Specific Function
Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
Gene Name
ALB
Uniprot ID
P02768
Uniprot Name
Serum albumin
Molecular Weight
69365.94 Da
References
  1. Abboud R, Akil M, Charcosset C, Greige-Gerges H: Interaction of glucocorticoids and progesterone derivatives with human serum albumin. Chem Phys Lipids. 2017 Oct;207(Pt B):271-278. doi: 10.1016/j.chemphyslip.2017.04.007. Epub 2017 Apr 21. [PubMed:28435101]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid binding
Specific Function
Major transport protein for glucocorticoids and progestins in the blood of almost all vertebrate species.
Gene Name
SERPINA6
Uniprot ID
P08185
Uniprot Name
Corticosteroid-binding globulin
Molecular Weight
45140.49 Da
References
  1. SANDBERG AA, SLAUNWHITE WR Jr, CARTER AC: Transcortin: a corticosteroid-binding protein of plasma. III. The effects of various steroids. J Clin Invest. 1960 Dec;39:1914-26. doi: 10.1172/JCI104216. [PubMed:13746120]

Drug created on June 13, 2005 07:24 / Updated on November 16, 2019 10:26