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Record Information
Version4.0
StatusDetected and Quantified
Creation Date2005-11-16 15:48:42 UTC
Update Date2018-05-20 10:02:32 UTC
HMDB IDHMDB0000015
Secondary Accession Numbers
  • HMDB00015
Metabolite Identification
Common NameCortexolone
DescriptionCortexolone is the precursor of cortisol. Accumulation of cortexolone can happen in a defect known as congenital adrenal hyperplasia, which is due to 11-beta-hydroxylase deficiency, resulting in androgen excess, virilization, and hypertension (PMID: 2022736 ). Cortexolone is a 17-hydroxycorticosteroid with glucocorticoid and anti-inflammatory activities (PubChem).
Structure
Thumb
Synonyms
ValueSource
11-Desoxy-17-hydroxycorticosteroneChEBI
CortodoxoneChEBI
11-DeoxycortisolChEMBL
SK&F 3050ChEMBL
Reichstein substance SHMDB
Substance S, reichstein'sHMDB
11 DeoxycortisolHMDB
11 DesoxycortisolHMDB
11 DesoxycortisoneHMDB
S, Reichstein's substanceHMDB
11-DesoxycortisolHMDB
11-DesoxycortisoneHMDB
Reichsteins substance SHMDB
Reichstein's substance SMeSH
CortexoloneMeSH
11-Deoxy-17-hydroxycorticosteroneHMDB
11-DeoxyhydrocortisoneHMDB
11-DesoxyhydrocortisoneHMDB
17,21-Dihydroxy-4-pregnene-3,20-dioneHMDB
17,21-Dihydroxypregn-4-ene-3,20-dioneHMDB
17,21-DihydroxyprogesteroneHMDB
17-Hydroxy-11-deoxycorticosteroneHMDB
17alpha-HydroxycortexoneHMDB
20-Dione 17,21-dihydroxypregn-4-ene-3HMDB
4-Pregnene-17alpha,21-diol-3,20-dioneHMDB
Compound SCAS
11-Deoxy-17-hydrocorticosteroneCAS
11-DeoxycortisoneCAS
11-Desoxy-17α-hydroxycorticosteroneCAS
11-Desoxy-17alpha-hydroxycorticosteroneGenerator
17,21-Dihydroxypregn-4-en-3,20-dioneCAS
17α,21-Dihydroxy-4-pregnen-3,20-dioneCAS
17α,21-Dihydroxypregn-4-ene-3,20-dioneCAS
17α,21-DihydroxyprogesteroneCAS
17α-HydroxycortexoneCAS
4-Pregnen-17α,21-diol-3,20-dioneCAS
4-Pregnene-17α,21-diol-3,20-dioneCAS
17alpha,21-Dihydroxy-4-pregnen-3,20-dioneGenerator
17alpha,21-Dihydroxypregn-4-ene-3,20-dioneGenerator
17alpha,21-DihydroxyprogesteroneGenerator
4-Pregnen-17alpha,21-diol-3,20-dioneGenerator
Chemical FormulaC21H30O4
Average Molecular Weight346.4605
Monoisotopic Molecular Weight346.214409448
IUPAC Name(1S,2R,10R,11S,14R,15S)-14-hydroxy-14-(2-hydroxyacetyl)-2,15-dimethyltetracyclo[8.7.0.0^{2,7}.0^{11,15}]heptadec-6-en-5-one
Traditional Name(1S,2R,10R,11S,14R,15S)-14-hydroxy-14-(2-hydroxyacetyl)-2,15-dimethyltetracyclo[8.7.0.0^{2,7}.0^{11,15}]heptadec-6-en-5-one
CAS Registry Number152-58-9
SMILES
[H][C@@]12CC[C@](O)(C(=O)CO)[C@@]1(C)CC[C@@]1([H])[C@@]2([H])CCC2=CC(=O)CC[C@]12C
InChI Identifier
InChI=1S/C21H30O4/c1-19-8-5-14(23)11-13(19)3-4-15-16(19)6-9-20(2)17(15)7-10-21(20,25)18(24)12-22/h11,15-17,22,25H,3-10,12H2,1-2H3/t15-,16+,17+,19+,20+,21+/m1/s1
InChI KeyWHBHBVVOGNECLV-OBQKJFGGSA-N
Chemical Taxonomy
Description 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.
KingdomOrganic compounds
Super ClassLipids and lipid-like molecules
ClassSteroids and steroid derivatives
Sub ClassHydroxysteroids
Direct Parent21-hydroxysteroids
Alternative Parents
Substituents
  • 21-hydroxysteroid
  • Progestogin-skeleton
  • Pregnane-skeleton
  • 20-oxosteroid
  • 3-oxo-delta-4-steroid
  • 3-oxosteroid
  • 17-hydroxysteroid
  • Oxosteroid
  • Delta-4-steroid
  • Cyclohexenone
  • Alpha-hydroxy ketone
  • Tertiary alcohol
  • Cyclic alcohol
  • Cyclic ketone
  • Ketone
  • Organic oxygen compound
  • Organooxygen compound
  • Primary alcohol
  • Carbonyl group
  • Hydrocarbon derivative
  • Alcohol
  • Organic oxide
  • Aliphatic homopolycyclic compound
Molecular FrameworkAliphatic homopolycyclic compounds
External Descriptors
Ontology
Disposition

Route of exposure:

Source:

Biological location:

Process

Naturally occurring process:

Role

Biological role:

Industrial application:

Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting Point215 °CNot Available
Boiling PointNot AvailableNot Available
Water SolubilityNot AvailableNot Available
LogP3.08SANGSTER (1994)
Predicted Properties
PropertyValueSource
Water Solubility0.025 g/LALOGPS
logP2.79ALOGPS
logP2.58ChemAxon
logS-4.1ALOGPS
pKa (Strongest Acidic)12.59ChemAxon
pKa (Strongest Basic)-3.3ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area74.6 ŲChemAxon
Rotatable Bond Count2ChemAxon
Refractivity95.81 m³·mol⁻¹ChemAxon
Polarizability38.86 ųChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
GC-MSGC-MS Spectrum - GC-MS (2 MEOX; 2 TMS)splash10-0fau-4920000000-b369d2b097d724e4d6d6View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-qTof , Positivesplash10-0a4j-3931000000-0d5b4b35af4fb7259e0bView in MoNA
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-0a4j-3931000000-0d5b4b35af4fb7259e0bView in MoNA
1D NMR13C NMR SpectrumNot AvailableView in JSpectraViewer
Biological Properties
Cellular Locations
  • Cytoplasm
  • Extracellular
  • Membrane (predicted from logP)
  • Mitochondria
  • Endoplasmic reticulum
Biospecimen Locations
  • Blood
  • Feces
  • Urine
Tissue Location
  • All Tissues
Pathways
Normal Concentrations
BiospecimenStatusValueAgeSexConditionReferenceDetails
BloodDetected and Quantified0.0039 +/- 0.0004 uMAdult (>18 years old)BothNormal details
BloodDetected and Quantified<0.0250 uMNot SpecifiedBothNormal details
BloodDetected and Quantified<0.0600 uMNewborn (0-30 days old)BothNormal details
FecesDetected but not Quantified Infant (0-1 year old)Both
Normal
details
UrineDetected and Quantified0.017-178.9 umol/mmol creatinineNewborn (0-30 days old)BothNormal details
UrineDetected and Quantified0.02 (0.0091-0.032) umol/mmol creatinineAdult (>18 years old)FemaleNormal details
Abnormal Concentrations
BiospecimenStatusValueAgeSexConditionReferenceDetails
BloodDetected and Quantified1.3 uMNewborn (0-30 days old)Female11-beta-hydroxylase deficiency details
BloodDetected and Quantified1.84 uMInfant (0-1 year old)Female11-beta-hydroxylase deficiency details
BloodDetected and Quantified0.00790-0.329 uMChildren (1-13 years old)Both11-beta-hydroxylase deficiency details
FecesDetected but not Quantified Newborn (0-30 days old)Both
Sepsis
details
Associated Disorders and Diseases
Disease References
11-beta-Hydroxylase deficiency
  1. Burren CP, Montalto J, Yong AB, Batch JA: CYP11 beta 1 (11-beta-hydroxylase) deficiency in congenital adrenal hyperplasia. J Paediatr Child Health. 1996 Oct;32(5):433-8. [PubMed:8933406 ]
Sepsis
  1. Stewart CJ, Embleton ND, Marrs ECL, Smith DP, Fofanova T, Nelson A, Skeath T, Perry JD, Petrosino JF, Berrington JE, Cummings SP: Longitudinal development of the gut microbiome and metabolome in preterm neonates with late onset sepsis and healthy controls. Microbiome. 2017 Jul 12;5(1):75. doi: 10.1186/s40168-017-0295-1. [PubMed:28701177 ]
Associated OMIM IDs
  • 202010 (11-beta-Hydroxylase deficiency)
DrugBank IDNot Available
Phenol Explorer Compound IDNot Available
FoodDB IDFDB021872
KNApSAcK IDNot Available
Chemspider ID389582
KEGG Compound IDC05488
BioCyc ID11-DEOXY-CORTISOL
BiGG ID45914
Wikipedia LinkCortexolone
METLIN ID5088
PubChem Compound440707
PDB IDNot Available
ChEBI ID28324
References
Synthesis ReferenceLuu, Duc Huy. New method for the synthesis of Reichstein's compound S from pregnene. Tap Chi Duoc Hoc (2002), (9), 23-25.
Material Safety Data Sheet (MSDS)Download (PDF)
General References
  1. White PC, Dupont J, New MI, Leiberman E, Hochberg Z, Rosler A: A mutation in CYP11B1 (Arg-448----His) associated with steroid 11 beta-hydroxylase deficiency in Jews of Moroccan origin. J Clin Invest. 1991 May;87(5):1664-7. [PubMed:2022736 ]
  2. White PC, Tusie-Luna MT, New MI, Speiser PW: Mutations in steroid 21-hydroxylase (CYP21). Hum Mutat. 1994;3(4):373-8. [PubMed:8081391 ]
  3. Curnow KM, Tusie-Luna MT, Pascoe L, Natarajan R, Gu JL, Nadler JL, White PC: The product of the CYP11B2 gene is required for aldosterone biosynthesis in the human adrenal cortex. Mol Endocrinol. 1991 Oct;5(10):1513-22. [PubMed:1775135 ]
  4. Mellon SH, Miller WL: Extraadrenal steroid 21-hydroxylation is not mediated by P450c21. J Clin Invest. 1989 Nov;84(5):1497-502. [PubMed:2808702 ]
  5. Homma K, Hasegawa T, Masumoto M, Takeshita E, Watanabe K, Chiba H, Kurosawa T, Takahashi T, Matsuo N: Reference values for urinary steroids in Japanese newborn infants: gas chromatography/mass spectrometry in selected ion monitoring. Endocr J. 2003 Dec;50(6):783-92. [PubMed:14709852 ]
  6. Trakakis E, Laggas D, Salamalekis E, Creatsas G: 21-Hydroxylase deficiency: from molecular genetics to clinical presentation. J Endocrinol Invest. 2005 Feb;28(2):187-92. [PubMed:15887869 ]
  7. Krone N, Riepe FG, Gotze D, Korsch E, Rister M, Commentz J, Partsch CJ, Grotzinger J, Peter M, Sippell WG: Congenital adrenal hyperplasia due to 11-hydroxylase deficiency: functional characterization of two novel point mutations and a three-base pair deletion in the CYP11B1 gene. J Clin Endocrinol Metab. 2005 Jun;90(6):3724-30. Epub 2005 Mar 8. [PubMed:15755848 ]
  8. Adinoff B, Krebaum SR, Chandler PA, Ye W, Brown MB, Williams MJ: Dissection of hypothalamic-pituitary-adrenal axis pathology in 1-month-abstinent alcohol-dependent men, part 1: adrenocortical and pituitary glucocorticoid responsiveness. Alcohol Clin Exp Res. 2005 Apr;29(4):517-27. [PubMed:15834216 ]
  9. Brown JR, Cavanaugh AH, Farnsworth WE: A simple radioimmunoassay for plasma cortisol and 11-deoxycortisol (17, 21-dihydroxy-4-pregnene-3, 20-dione). Steroids. 1976 Oct;28(4):487-98. [PubMed:1034356 ]
  10. den Brinker M, Joosten KF, Liem O, de Jong FH, Hop WC, Hazelzet JA, van Dijk M, Hokken-Koelega AC: Adrenal insufficiency in meningococcal sepsis: bioavailable cortisol levels and impact of interleukin-6 levels and intubation with etomidate on adrenal function and mortality. J Clin Endocrinol Metab. 2005 Sep;90(9):5110-7. Epub 2005 Jun 28. [PubMed:15985474 ]
  11. Lee HH, Won GS, Chao HT, Lee YJ, Chung BC: Novel missense mutations, GCC [Ala306]- > GTC [Val] and ACG [Thr318]- > CCG [Pro], in the CYP11B1 gene cause steroid 11beta-hydroxylase deficiency in the Chinese. Clin Endocrinol (Oxf). 2005 Apr;62(4):418-22. [PubMed:15807871 ]
  12. Zachmann M, Tassinari D, Prader A: Clinical and biochemical variability of congenital adrenal hyperplasia due to 11 beta-hydroxylase deficiency. A study of 25 patients. J Clin Endocrinol Metab. 1983 Feb;56(2):222-9. [PubMed:6296182 ]
  13. Bradshaw KD, Milewich L, Mason JI, Parker CR Jr, MacDonald PC, Carr BR: Steroid secretory characteristics of a virilizing adrenal adenoma in a woman. J Endocrinol. 1994 Feb;140(2):297-307. [PubMed:8169562 ]
  14. Bureik M, Bruck N, Hubel K, Bernhardt R: The human mineralocorticoid receptor only partially differentiates between different ligands after expression in fission yeast. FEMS Yeast Res. 2005 Apr;5(6-7):627-33. [PubMed:15780662 ]
  15. Dragan CA, Zearo S, Hannemann F, Bernhardt R, Bureik M: Efficient conversion of 11-deoxycortisol to cortisol (hydrocortisone) by recombinant fission yeast Schizosaccharomyces pombe. FEMS Yeast Res. 2005 Apr;5(6-7):621-5. [PubMed:15780661 ]
  16. Sakamoto N, Matsukura S, Tsuboi S, Tokumiya T, Imura H: Radioimmunoassay for 11-deoxycortisol using iodine-labeled tracer. Endocrinol Jpn. 1976 Aug;23(4):359-63. [PubMed:1024042 ]
  17. Tjeerdsma G, Sluiter WJ, Hew JM, Molenaar WM, de Lange WE, Dullaart RP: Hyperprolactinaemia is associated with a higher prevalence of pituitary-adrenal dysfunction in non-functioning pituitary macroadenoma. Eur J Endocrinol. 1996 Sep;135(3):299-308. [PubMed:8890720 ]
  18. Hughes IA, Arisaka O, Perry LA, Honour JW: Early diagnosis of 11 beta-hydroxylase deficiency in two siblings confirmed by analysis of a novel steroid metabolite in newborn urine. Acta Endocrinol (Copenh). 1986 Mar;111(3):349-54. [PubMed:3515819 ]
  19. Simons K, Toomre D: Lipid rafts and signal transduction. Nat Rev Mol Cell Biol. 2000 Oct;1(1):31-9. [PubMed:11413487 ]
  20. Watson AD: Thematic review series: systems biology approaches to metabolic and cardiovascular disorders. Lipidomics: a global approach to lipid analysis in biological systems. J Lipid Res. 2006 Oct;47(10):2101-11. Epub 2006 Aug 10. [PubMed:16902246 ]
  21. Sethi JK, Vidal-Puig AJ: Thematic review series: adipocyte biology. Adipose tissue function and plasticity orchestrate nutritional adaptation. J Lipid Res. 2007 Jun;48(6):1253-62. Epub 2007 Mar 20. [PubMed:17374880 ]
  22. Lingwood D, Simons K: Lipid rafts as a membrane-organizing principle. Science. 2010 Jan 1;327(5961):46-50. doi: 10.1126/science.1174621. [PubMed:20044567 ]
  23. Gunstone, Frank D., John L. Harwood, and Albert J. Dijkstra (2007). The lipid handbook with CD-ROM. CRC Press.

Enzymes

General function:
Involved in monooxygenase activity
Specific function:
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.
Gene Name:
CYP11B1
Uniprot ID:
P15538
Molecular weight:
57572.44
Reactions
Cortexolone + Reduced ferredoxin + Oxygen → Hydrocortisone + Oxidized ferredoxin + Waterdetails
References
  1. Curnow KM, Tusie-Luna MT, Pascoe L, Natarajan R, Gu JL, Nadler JL, White PC: The product of the CYP11B2 gene is required for aldosterone biosynthesis in the human adrenal cortex. Mol Endocrinol. 1991 Oct;5(10):1513-22. [PubMed:1775135 ]
General function:
Involved in sequence-specific DNA binding transcription factor activity
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 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
Gene Name:
NR3C2
Uniprot ID:
P08235
Molecular weight:
107066.6
General function:
Involved in 3-beta-hydroxy-delta5-steroid dehydrogenase activity
Specific function:
3-beta-HSD is a bifunctional enzyme, that catalyzes the oxidative conversion of Delta(5)-ene-3-beta-hydroxy steroid, and the oxidative conversion of ketosteroids. The 3-beta-HSD enzymatic system plays a crucial role in the biosynthesis of all classes of hormonal steroids. Efficiently catalyzes the transformation of pregnenolone to progesterone, 17-alpha-hydroxypregnenolone to 17-alpha-hydroxyprogesterone, DHEA to 4-androstenedione, dihydrotestosterone to 5-alpha-androstane-3 beta,17 beta-diol, dehydroepiandrosterone to androstenedione and 5-alpha-androstan-3 beta,17 beta-diol to 5-alpha-dihydrotestosterone.
Gene Name:
HSD3B1
Uniprot ID:
P14060
Molecular weight:
42251.25
Reactions
Cortexolone + Hydrogen Ion + NADH → 17alpha,21-Dihydroxypregnenolone + NADdetails
General function:
Involved in 3-beta-hydroxy-delta5-steroid dehydrogenase activity
Specific function:
3-beta-HSD is a bifunctional enzyme, that catalyzes the oxidative conversion of Delta(5)-ene-3-beta-hydroxy steroid, and the oxidative conversion of ketosteroids. The 3-beta-HSD enzymatic system plays a crucial role in the biosynthesis of all classes of hormonal steroids.
Gene Name:
HSD3B2
Uniprot ID:
P26439
Molecular weight:
42051.845
Reactions
Cortexolone + Hydrogen Ion + NADH → 17alpha,21-Dihydroxypregnenolone + NADdetails
General function:
Involved in monooxygenase activity
Specific function:
Preferentially catalyzes the conversion of 11-deoxycorticosterone to aldosterone via corticosterone and 18-hydroxycorticosterone.
Gene Name:
CYP11B2
Uniprot ID:
P19099
Molecular weight:
57559.62
Reactions
Cortexolone + Reduced ferredoxin + Oxygen → Hydrocortisone + Oxidized ferredoxin + Waterdetails
General function:
Involved in monooxygenase activity
Specific function:
Not Available
Gene Name:
P450-CYP21B
Uniprot ID:
Q16874
Molecular weight:
56000.9
General function:
Involved in monooxygenase activity
Specific function:
Not Available
Gene Name:
CYP21A2
Uniprot ID:
Q08AG9
Molecular weight:
55972.9
General function:
Not Available
Specific function:
Specifically catalyzes the 21-hydroxylation of steroids. Required for the adrenal synthesis of mineralocorticoids and glucocorticoids.
Gene Name:
CYP21A2
Uniprot ID:
P08686
Molecular weight:
56000.94
Reactions
17-Hydroxyprogesterone + Reduced acceptor + Oxygen → Cortexolone + Acceptor + Waterdetails