Cortisone acetate

Identification

Summary

Cortisone acetate is a steroid hormone used for the relief of the inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses and endocrine disorders associated with inadequate production of steroid hormones.

Generic Name
Cortisone acetate
DrugBank Accession Number
DB01380
Background

Cortisone acetate was first isolate in 1935 and became more widely researched in 1949.1 Since then, glucocorticoids such as cortisone acetate have been used to treat a number of inflammatory conditions such as endocrine, rheumatic, collagen, dermatologic, allergic, ophthalmic, respiratory, hematologic, neoplastic, edematous, and gastrointestinal diseases and disorders.2,8

Cortisone acetate was granted FDA approval on 13 June 1950.7

Type
Small Molecule
Groups
Approved, Investigational
Structure
Weight
Average: 402.4807
Monoisotopic: 402.204238692
Chemical Formula
C23H30O6
Synonyms
  • Cortisone 21-acetate
  • Cortisone acetate
  • Cortone acetate

Pharmacology

Indication

Cortisone acetate is indicated to treat a wide variety of endocrine, rheumatic, collagen, dermatologic, allergic, ophthalmic, respiratory, hematologic, neoplastic, edematous, and gastrointestinal diseases and disorders.2,8

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Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Management ofAcne rosacea••••••••••••
Management ofAcquired hemolytic anemia••••••••••••
Management ofAcute gouty arthritis••••••••••••
Management ofAcute leukemia••••••••••••
Diagnostic agentAdrenocortical hyperfunction••••••••••••
Contraindications & Blackbox Warnings
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Pharmacodynamics

Corticosteroids bind to the glucocorticoid receptor, inhibiting pro-inflammatory signals, and promoting anti-inflammatory signals.3 The duration of action is moderate as it is generally given once daily.8 Corticosteroids have a wide therapeutic window as patients may require doses that are multiples of what the body naturally produces.3 Patients taking corticosteroids should be counselled regarding the risk of hypothalamic-pituitary-adrenal axis suppression and increased susceptibility to infections.3

Mechanism of action

The short term effects of corticosteroids are decreased vasodilation and permeability of capillaries, as well as decreased leukocyte migration to sites of inflammation.3 Corticosteroids binding to the glucocorticoid receptor mediates changes in gene expression that lead to multiple downstream effects over hours to days.3 Glucocorticoids inhibit neutrophil apoptosis and demargination; they inhibit phospholipase A2, which decreases the formation of arachidonic acid derivatives; they inhibit NF-Kappa B and other inflammatory transcription factors; they promote anti-inflammatory genes like interleukin-10.3 Lower doses of corticosteroids provide an anti-inflammatory effect, while higher doses are immunosuppressive.3 High doses of glucocorticoids for an extended period bind to the mineralocorticoid receptor, raising sodium levels and decreasing potassium levels.3

TargetActionsOrganism
ASteroid hormone receptor ERR2
modulator
Humans
AEstrogen-related receptor gamma
modulator
Humans
AGlucocorticoid receptor
agonist
Humans
ASteroid hormone receptor ERR1
modulator
Humans
UAnnexin A1
inducer
Humans
Absorption

Not Available

Volume of distribution

Not Available

Protein binding

Corticosteroids are generally bound to corticosteroid binding globulin5 and serum albumin4 in plasma.

Metabolism
Not Available
Route of elimination

Corticosteroids are eliminated predominantly in the urine.4

Half-life

Not Available

Clearance

Data regarding the clearance of cortisone acetate is not readily available.8

Adverse Effects
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Toxicity

Data regarding acute overdoses of glucocorticoids are rare.8 Chronic high doses of glucocorticoids can lead to the development of cataract, glaucoma, hypertension, water retention, hyperlipidemia, peptic ulcer, pancreatitis, myopathy, osteoporosis, mood changes, psychosis, dermal atrophy, allergy, acne, hypertrichosis, immune suppression, decreased resistance to infection, moon face, hyperglycemia, hypocalcemia, hypophosphatemia, metabolic acidosis, growth suppression, and secondary adrenal insufficiency.6 Overdose may be treated by adjusting the dose or stopping the corticosteroid as well as initiating symptomatic and supportive treatment.6

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
AbametapirThe serum concentration of Cortisone acetate can be increased when it is combined with Abametapir.
AbataceptThe risk or severity of adverse effects can be increased when Abatacept is combined with Cortisone acetate.
AbemaciclibThe metabolism of Abemaciclib can be increased when combined with Cortisone acetate.
AcalabrutinibThe metabolism of Acalabrutinib can be increased when combined with Cortisone acetate.
AcarboseThe risk or severity of hyperglycemia can be increased when Cortisone acetate is combined with Acarbose.
Food Interactions
  • Take with food. Taking cortisone acetate with food may reduce gastrointestinal upset.

Products

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Active Moieties
NameKindUNIICASInChI Key
CortisoneprodrugV27W9254FZ53-06-5MFYSYFVPBJMHGN-ZPOLXVRWSA-N
Product Images
International/Other Brands
Cortisyl
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Cortisone AcetateTablet10 mg/1OralUNSPECIFIED2006-01-04Not applicableUS flag
Cortisone AcetateTablet5 mg/1OralUNSPECIFIED2006-01-04Not applicableUS flag
Cortisone AcetateTablet25 mgOralBausch Health, Canada Inc.1973-12-31Not applicableCanada flag
Cortone Sus 50mg/mlSuspension50 mg / mLIntramuscularMerck Frosst Canada & Cie, Merck Frosst Canada & Co.1951-12-311999-08-06Canada flag
Cortone Tab 25mgTablet25 mgOralMerck Frosst Canada & Cie, Merck Frosst Canada & Co.1954-12-312002-07-29Canada flag
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Cortisone AcetateTablet25 mg/1OralGolden State Medical Supply, Inc.1972-06-132017-01-02US flag
Cortisone AcetateTablet25 mg/1OralChartwell Rx, Llc1974-10-17Not applicableUS flag
Cortisone AcetateTablet25 mg/1OralHikma Pharmaceuticals USA Inc.2013-08-26Not applicableUS flag
Cortisone AcetateTablet25 mg/1OralHikma Pharmaceuticals USA Inc.1972-06-13Not applicableUS flag
Cortisone AcetateTablet25 mg/1OralHikma Pharmaceuticals USA Inc.2013-08-22Not applicableUS flag

Categories

Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as gluco/mineralocorticoids, progestogins and derivatives. These are steroids with a structure based on a hydroxylated prostane moiety.
Kingdom
Organic compounds
Super Class
Lipids and lipid-like molecules
Class
Steroids and steroid derivatives
Sub Class
Pregnane steroids
Direct Parent
Gluco/mineralocorticoids, progestogins and derivatives
Alternative Parents
20-oxosteroids / 3-oxo delta-4-steroids / 17-hydroxysteroids / 11-oxosteroids / Delta-4-steroids / Cyclohexenones / Alpha-acyloxy ketones / Tertiary alcohols / Alpha-hydroxy ketones / Cyclic alcohols and derivatives
show 4 more
Substituents
11-oxosteroid / 17-hydroxysteroid / 20-oxosteroid / 3-oxo-delta-4-steroid / 3-oxosteroid / Alcohol / Aliphatic homopolycyclic compound / Alpha-acyloxy ketone / Alpha-hydroxy ketone / Carbonyl group
show 16 more
Molecular Framework
Aliphatic homopolycyclic compounds
External Descriptors
corticosteroid hormone (CHEBI:3897) / C21 steroids (gluco/mineralocorticoids, progestogens) and derivatives (C08173) / C21 steroids (gluco/mineralocorticoids, progestogins) and derivatives (LMST02030120)
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
883WKN7W8X
CAS number
50-04-4
InChI Key
ITRJWOMZKQRYTA-RFZYENFJSA-N
InChI
InChI=1S/C23H30O6/c1-13(24)29-12-19(27)23(28)9-7-17-16-5-4-14-10-15(25)6-8-21(14,2)20(16)18(26)11-22(17,23)3/h10,16-17,20,28H,4-9,11-12H2,1-3H3/t16-,17-,20+,21-,22-,23-/m0/s1
IUPAC Name
2-[(1R,3aS,3bS,9aR,9bS,11aS)-1-hydroxy-9a,11a-dimethyl-7,10-dioxo-1H,2H,3H,3aH,3bH,4H,5H,7H,8H,9H,9aH,9bH,10H,11H,11aH-cyclopenta[a]phenanthren-1-yl]-2-oxoethyl acetate
SMILES
[H][C@@]12CC[C@](O)(C(=O)COC(C)=O)[C@@]1(C)CC(=O)[C@@]1([H])[C@@]2([H])CCC2=CC(=O)CC[C@]12C

References

Synthesis Reference

Reichstein,T.; US. Patent 2,403,683; July 9, 1946. Gallagher,T.F.; US. Patent 2,447,325; August 17,1948; assigned to Research Corporation. Sarett, L.H.; U.S. Patent 2,541,104; February 13, 1951; assigned to Merck & Co., Inc.

General References
  1. BOLAND EW, HEADLEY NE: Effects of cortisone acetate on rheumatoid arthritis. J Am Med Assoc. 1949 Oct 1;141(5):301-8. doi: 10.1001/jama.1949.02910050001001. [Article]
  2. Hardy RS, Raza K, Cooper MS: Therapeutic glucocorticoids: mechanisms of actions in rheumatic diseases. Nat Rev Rheumatol. 2020 Mar;16(3):133-144. doi: 10.1038/s41584-020-0371-y. Epub 2020 Feb 7. [Article]
  3. Yasir M, Sonthalia S: Corticosteroid Adverse Effects . [Article]
  4. Czock D, Keller F, Rasche FM, Haussler U: Pharmacokinetics and pharmacodynamics of systemically administered glucocorticoids. Clin Pharmacokinet. 2005;44(1):61-98. doi: 10.2165/00003088-200544010-00003. [Article]
  5. Gardill BR, Vogl MR, Lin HY, Hammond GL, Muller YA: Corticosteroid-binding globulin: structure-function implications from species differences. PLoS One. 2012;7(12):e52759. doi: 10.1371/journal.pone.0052759. Epub 2012 Dec 26. [Article]
  6. Ciriaco M, Ventrice P, Russo G, Scicchitano M, Mazzitello G, Scicchitano F, Russo E: Corticosteroid-related central nervous system side effects. J Pharmacol Pharmacother. 2013 Dec;4(Suppl 1):S94-8. doi: 10.4103/0976-500X.120975. [Article]
  7. FDA Approved Drug Products: Cortone Cortisone Acetate Injection (Discontinued) [Link]
  8. DailyMed Label: Cortisone acetate tablet [Link]
Human Metabolome Database
HMDB0015459
KEGG Drug
D00973
KEGG Compound
C08173
PubChem Compound
5745
PubChem Substance
46508852
ChemSpider
5543
BindingDB
50455157
RxNav
21655
ChEBI
3897
ChEMBL
CHEMBL1650
ZINC
ZINC000003875334
PharmGKB
PA449130
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Cortisone_acetate
MSDS
Download (74.3 KB)

Clinical Trials

Clinical Trials
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PhaseStatusPurposeConditionsCountStart DateWhy Stopped100+ additional columns
4CompletedTreatmentPrimary adrenocoritical insufficiency / Secondary Adrenal Insufficiency1somestatusstop reasonjust information to hide
4Unknown StatusTreatmentCongenital Adrenal Hyperplasia (CAH)1somestatusstop reasonjust information to hide
3CompletedTreatmentAcute ACE-induced Angioedema1somestatusstop reasonjust information to hide
3CompletedTreatmentAdrenal Insufficiency1somestatusstop reasonjust information to hide
2Unknown StatusTreatmentCongenital Adrenal Hyperplasia (CAH)1somestatusstop reasonjust information to hide

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Bergen Brunswig
  • Consolidated Midland Corp.
  • CVS Pharmacy
  • Major Pharmaceuticals
  • Medicine Shop
  • Medisca Inc.
  • Murfreesboro Pharmaceutical Nursing Supply
  • Pharmacia Inc.
  • Qualitest
  • West-Ward Pharmaceuticals
Dosage Forms
FormRouteStrength
Injection
Injection25 MG/ML
TabletOral10 mg/1
TabletOral25 mg/1
TabletOral5 mg/1
TabletOral25 MG
SuspensionIntramuscular50 mg / mL
TabletOral5 mg
Prices
Unit descriptionCostUnit
Cortisone acetate powder24.18USD g
Cortisone Acetate 25 mg Tablet0.47USD tablet
Cortisone 25 mg tablet0.46USD tablet
Cortaid 1% cream0.21USD g
CVS Pharmacy cortisone 1% cream0.18USD g
CVS Pharmacy anti-itch 1% cream0.13USD g
Hydrocortisone 0.5% cream0.11USD g
Medi-cortisone 1% cream0.1USD g
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)227-229Reichstein,T.; US. Patent 2,403,683; July 9, 1946. Gallagher,T.F.; US. Patent 2,447,325; August 17,1948; assigned to Research Corporation. Sarett, L.H.; U.S. Patent 2,541,104; February 13, 1951; assigned to Merck & Co., Inc.
water solubility20 mg/L (at 25 °C)YALKOWSKY,SH & DANNENFELSER,RM (1992)
logP2.10HANSCH,C ET AL. (1995)
Predicted Properties
PropertyValueSource
Water Solubility0.0278 mg/mLALOGPS
logP2.35ALOGPS
logP2.1Chemaxon
logS-4.2ALOGPS
pKa (Strongest Acidic)12.6Chemaxon
pKa (Strongest Basic)-3.8Chemaxon
Physiological Charge0Chemaxon
Hydrogen Acceptor Count5Chemaxon
Hydrogen Donor Count1Chemaxon
Polar Surface Area97.74 Å2Chemaxon
Rotatable Bond Count4Chemaxon
Refractivity105.63 m3·mol-1Chemaxon
Polarizability43.06 Å3Chemaxon
Number of Rings4Chemaxon
Bioavailability1Chemaxon
Rule of FiveYesChemaxon
Ghose FilterYesChemaxon
Veber's RuleNoChemaxon
MDDR-like RuleNoChemaxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.983
Blood Brain Barrier+0.9851
Caco-2 permeable-0.6606
P-glycoprotein substrateSubstrate0.7382
P-glycoprotein inhibitor IInhibitor0.7341
P-glycoprotein inhibitor IIInhibitor0.5925
Renal organic cation transporterNon-inhibitor0.7452
CYP450 2C9 substrateNon-substrate0.8551
CYP450 2D6 substrateNon-substrate0.9294
CYP450 3A4 substrateSubstrate0.7841
CYP450 1A2 substrateNon-inhibitor0.9045
CYP450 2C9 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorNon-inhibitor0.9556
CYP450 2C19 inhibitorNon-inhibitor0.9026
CYP450 3A4 inhibitorNon-inhibitor0.8588
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9246
Ames testNon AMES toxic0.9409
CarcinogenicityNon-carcinogens0.9551
BiodegradationNot ready biodegradable0.9354
Rat acute toxicity2.1280 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9599
hERG inhibition (predictor II)Non-inhibitor0.6638
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-MSsplash10-00dl-5769000000-0de043e0ef22a3c233ec
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSsplash10-0udi-0643900000-f8c82718aaac7d5f1097
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSsplash10-0udi-3900000000-f12188734d2d15075e1a
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0udi-0643900000-f8c82718aaac7d5f1097
MS/MS Spectrum - , positiveLC-MS/MSsplash10-03di-2941000000-b0ec70aa310131ced784
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-000i-0009100000-a446cbe04b2134ad1884
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-0k96-9005400000-64fde279722754e8fdbd
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-0lyc-1669100000-1fd8d42aba77f66a9c2d
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-0a4i-9007000000-56d4e90793e41e09c899
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-0pba-9064100000-7f60c359f9f5662bb735
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-08fu-0943000000-000ebe2ac7b055b9ea9d
Predicted 1H NMR Spectrum1D NMRNot Applicable
Predicted 13C NMR Spectrum1D NMRNot Applicable
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-209.2040396
predicted
DarkChem Lite v0.1.0
[M-H]-206.7025396
predicted
DarkChem Lite v0.1.0
[M-H]-210.4518396
predicted
DarkChem Lite v0.1.0
[M-H]-203.05083
predicted
DeepCCS 1.0 (2019)
[M+H]+209.4531396
predicted
DarkChem Lite v0.1.0
[M+H]+206.8732396
predicted
DarkChem Lite v0.1.0
[M+H]+209.7077396
predicted
DarkChem Lite v0.1.0
[M+H]+204.94624
predicted
DeepCCS 1.0 (2019)
[M+Na]+209.6649396
predicted
DarkChem Lite v0.1.0
[M+Na]+206.5763396
predicted
DarkChem Lite v0.1.0
[M+Na]+210.3525396
predicted
DarkChem Lite v0.1.0
[M+Na]+211.80598
predicted
DeepCCS 1.0 (2019)

Targets

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Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Modulator
General Function
Transcription factor that binds a canonical ESRRB recognition (ERRE) sequence 5'TCAAGGTCA-3' localized on promoter and enhancer of targets genes regulating their expression or their transcription activity (PubMed:17920186, PubMed:19755138). Plays a role, in a LIF-independent manner, in maintainance of self-renewal and pluripotency of embryonic and trophoblast stem cells through different signaling pathways including FGF signaling pathway and Wnt signaling pathways. Upon FGF signaling pathway activation, interacts with KDM1A by directly binding to enhancer site of ELF5 and EOMES and activating their transcription leading to self-renewal of trophoblast stem cells. Also regulates expression of multiple rod-specific genes and is required for survival of this cell type (By similarity). Plays a role as transcription factor activator of GATA6, NR0B1, POU5F1 and PERM1 (PubMed:23836911). Plays a role as transcription factor repressor of NFE2L2 transcriptional activity and ESR1 transcriptional activity (PubMed:17920186, PubMed:19755138). During mitosis remains bound to a subset of interphase target genes, including pluripotency regulators, through the canonical ESRRB recognition (ERRE) sequence, leading to their transcriptional activation in early G1 phase. Can coassemble on structured DNA elements with other transcription factors like SOX2, POU5F1, KDM1A and NCOA3 to trigger ESRRB-dependent gene activation. This mechanism, in the case of SOX2 corecruitment prevents the embryonic stem cells (ESCs) to epiblast stem cells (EpiSC) transition through positive regulation of NR0B1 that inhibits the EpiSC transcriptional program. Also plays a role inner ear development by controlling expression of ion channels and transporters and in early placentation (By similarity)
Specific Function
cis-regulatory region sequence-specific DNA binding
Gene Name
ESRRB
Uniprot ID
O95718
Uniprot Name
Steroid hormone receptor ERR2
Molecular Weight
48053.14 Da
References
  1. Zhou Y, Zhang Y, Zhao D, Yu X, Shen X, Zhou Y, Wang S, Qiu Y, Chen Y, Zhu F: TTD: Therapeutic Target Database describing target druggability information. Nucleic Acids Res. 2024 Jan 5;52(D1):D1465-D1477. doi: 10.1093/nar/gkad751. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Modulator
General Function
Orphan receptor that acts as a transcription activator in the absence of bound ligand. Binds specifically to an estrogen response element and activates reporter genes controlled by estrogen response elements (By similarity). Induces the expression of PERM1 in the skeletal muscle
Specific Function
AF-2 domain binding
Gene Name
ESRRG
Uniprot ID
P62508
Uniprot Name
Estrogen-related receptor gamma
Molecular Weight
51305.485 Da
References
  1. Zhou Y, Zhang Y, Zhao D, Yu X, Shen X, Zhou Y, Wang S, Qiu Y, Chen Y, Zhu F: TTD: Therapeutic Target Database describing target druggability information. Nucleic Acids Res. 2024 Jan 5;52(D1):D1465-D1477. doi: 10.1093/nar/gkad751. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Agonist
General Function
Receptor for glucocorticoids (GC) (PubMed:27120390, PubMed:37478846). 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 modulator of other transcription factors (PubMed:28139699). Affects inflammatory responses, cellular proliferation and differentiation in target tissues. Involved in chromatin remodeling (PubMed:9590696). Plays a role in rapid mRNA degradation by binding to the 5' UTR of target mRNAs and interacting with PNRC2 in a ligand-dependent manner which recruits the RNA helicase UPF1 and the mRNA-decapping enzyme DCP1A, leading to RNA decay (PubMed:25775514). Could act as a coactivator for STAT5-dependent transcription upon growth hormone (GH) stimulation and could reveal an essential role of hepatic GR in the control of body growth (By similarity)
Specific Function
core promoter sequence-specific DNA binding
Gene Name
NR3C1
Uniprot ID
P04150
Uniprot Name
Glucocorticoid receptor
Molecular Weight
85658.57 Da
References
  1. Grossman R, Yehuda R, Golier J, McEwen B, Harvey P, Maria NS: Cognitive effects of intravenous hydrocortisone in subjects with PTSD and healthy control subjects. Ann N Y Acad Sci. 2006 Jul;1071:410-21. [Article]
  2. Rautanen A, Eriksson JG, Kere J, Andersson S, Osmond C, Tienari P, Sairanen H, Barker DJ, Phillips DI, Forsen T, Kajantie E: Associations of body size at birth with late-life cortisol concentrations and glucose tolerance are modified by haplotypes of the glucocorticoid receptor gene. J Clin Endocrinol Metab. 2006 Nov;91(11):4544-51. Epub 2006 Aug 8. [Article]
  3. Hammer F, Stewart PM: Cortisol metabolism in hypertension. Best Pract Res Clin Endocrinol Metab. 2006 Sep;20(3):337-53. [Article]
  4. Shaw JR, Gabor K, Hand E, Lankowski A, Durant L, Thibodeau R, Stanton CR, Barnaby R, Coutermarsh B, Karlson KH, Sato JD, Hamilton JW, Stanton BA: Role of glucocorticoid receptor in acclimation of killifish (Fundulus heteroclitus) to seawater and effects of arsenic. Am J Physiol Regul Integr Comp Physiol. 2007 Feb;292(2):R1052-60. Epub 2006 Oct 12. [Article]
  5. Sher L: Combined dexamethasone suppression-corticotropin-releasing hormone stimulation test in studies of depression, alcoholism, and suicidal behavior. ScientificWorldJournal. 2006 Oct 31;6:1398-404. [Article]
  6. Schlechte JA, Ginsberg BH, Sherman BM: Regulation of the glucocorticoid receptor in human lymphocytes. J Steroid Biochem. 1982 Jan;16(1):69-74. [Article]
  7. Schlechte JA, Sherman BM: Decreased glucocorticoid receptor binding in adrenal insufficiency. J Clin Endocrinol Metab. 1982 Jan;54(1):145-9. [Article]
  8. DailyMed Label: Cortisone acetate tablet [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Modulator
General Function
Binds to an ERR-alpha response element (ERRE) containing a single consensus half-site, 5'-TNAAGGTCA-3'. Can bind to the medium-chain acyl coenzyme A dehydrogenase (MCAD) response element NRRE-1 and may act as an important regulator of MCAD promoter. Binds to the C1 region of the lactoferrin gene promoter. Requires dimerization and the coactivator, PGC-1A, for full activity. The ERRalpha/PGC1alpha complex is a regulator of energy metabolism. Induces the expression of PERM1 in the skeletal muscle
Specific Function
DNA-binding transcription factor activity
Gene Name
ESRRA
Uniprot ID
P11474
Uniprot Name
Steroid hormone receptor ERR1
Molecular Weight
45509.11 Da
References
  1. Zhou Y, Zhang Y, Zhao D, Yu X, Shen X, Zhou Y, Wang S, Qiu Y, Chen Y, Zhu F: TTD: Therapeutic Target Database describing target druggability information. Nucleic Acids Res. 2024 Jan 5;52(D1):D1465-D1477. doi: 10.1093/nar/gkad751. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inducer
General Function
Plays important roles in the innate immune response as effector of glucocorticoid-mediated responses and regulator of the inflammatory process. Has anti-inflammatory activity (PubMed:8425544). Plays a role in glucocorticoid-mediated down-regulation of the early phase of the inflammatory response (By similarity). Contributes to the adaptive immune response by enhancing signaling cascades that are triggered by T-cell activation, regulates differentiation and proliferation of activated T-cells (PubMed:17008549). Promotes the differentiation of T-cells into Th1 cells and negatively regulates differentiation into Th2 cells (PubMed:17008549). Has no effect on unstimulated T cells (PubMed:17008549). Negatively regulates hormone exocytosis via activation of the formyl peptide receptors and reorganization of the actin cytoskeleton (PubMed:19625660). Has high affinity for Ca(2+) and can bind up to eight Ca(2+) ions (By similarity). Displays Ca(2+)-dependent binding to phospholipid membranes (PubMed:2532504, PubMed:8557678). Plays a role in the formation of phagocytic cups and phagosomes. Plays a role in phagocytosis by mediating the Ca(2+)-dependent interaction between phagosomes and the actin cytoskeleton (By similarity)
Specific Function
cadherin binding involved in cell-cell adhesion
Gene Name
ANXA1
Uniprot ID
P04083
Uniprot Name
Annexin A1
Molecular Weight
38713.855 Da
References
  1. Serres M, Viac J, Comera C, Schmitt D: Expression of annexin I in freshly isolated human epidermal cells and in cultured keratinocytes. Arch Dermatol Res. 1994;286(5):268-72. [Article]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inducer
General Function
A cytochrome P450 monooxygenase involved in the metabolism of sterols, steroid hormones, retinoids and fatty acids (PubMed:10681376, PubMed:11093772, PubMed:11555828, PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:19965576, PubMed:20702771, PubMed:21490593, PubMed:21576599). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase). Catalyzes the hydroxylation of carbon-hydrogen bonds (PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:21490593, PubMed:21576599, PubMed:2732228). Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1) and 17beta-estradiol (E2), namely 2-hydroxy E1 and E2, as well as D-ring hydroxylated E1 and E2 at the C-16 position (PubMed:11555828, PubMed:12865317, PubMed:14559847). Plays a role in the metabolism of androgens, particularly in oxidative deactivation of testosterone (PubMed:15373842, PubMed:15764715, PubMed:22773874, PubMed:2732228). Metabolizes testosterone to less biologically active 2beta- and 6beta-hydroxytestosterones (PubMed:15373842, PubMed:15764715, PubMed:2732228). Contributes to the formation of hydroxycholesterols (oxysterols), particularly A-ring hydroxylated cholesterol at the C-4beta position, and side chain hydroxylated cholesterol at the C-25 position, likely contributing to cholesterol degradation and bile acid biosynthesis (PubMed:21576599). Catalyzes bisallylic hydroxylation of polyunsaturated fatty acids (PUFA) (PubMed:9435160). Catalyzes the epoxidation of double bonds of PUFA with a preference for the last double bond (PubMed:19965576). Metabolizes endocannabinoid arachidonoylethanolamide (anandamide) to 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed:20702771). Plays a role in the metabolism of retinoids. Displays high catalytic activity for oxidation of all-trans-retinol to all-trans-retinal, a rate-limiting step for the biosynthesis of all-trans-retinoic acid (atRA) (PubMed:10681376). Further metabolizes atRA toward 4-hydroxyretinoate and may play a role in hepatic atRA clearance (PubMed:11093772). Responsible for oxidative metabolism of xenobiotics. Acts as a 2-exo-monooxygenase for plant lipid 1,8-cineole (eucalyptol) (PubMed:11159812). Metabolizes the majority of the administered drugs. Catalyzes sulfoxidation of the anthelmintics albendazole and fenbendazole (PubMed:10759686). Hydroxylates antimalarial drug quinine (PubMed:8968357). Acts as a 1,4-cineole 2-exo-monooxygenase (PubMed:11695850). Also involved in vitamin D catabolism and calcium homeostasis. Catalyzes the inactivation of the active hormone calcitriol (1-alpha,25-dihydroxyvitamin D(3)) (PubMed:29461981)
Specific Function
1,8-cineole 2-exo-monooxygenase activity
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Ekins S, Bravi G, Wikel JH, Wrighton SA: Three-dimensional-quantitative structure activity relationship analysis of cytochrome P-450 3A4 substrates. J Pharmacol Exp Ther. 1999 Oct;291(1):424-33. [Article]
  2. Luo X, Zhu LJ, Cai NF, Zheng LY, Cheng ZN: Prediction of tacrolimus metabolism and dosage requirements based on CYP3A4 phenotype and CYP3A5(*)3 genotype in Chinese renal transplant recipients. Acta Pharmacol Sin. 2016 Apr;37(4):555-60. doi: 10.1038/aps.2015.163. Epub 2016 Feb 29. [Article]
  3. Flockhart Table of Drug Interactions [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inducer
General Function
A cytochrome P450 monooxygenase involved in the metabolism of steroid hormones and vitamins (PubMed:10681376, PubMed:11093772, PubMed:12865317, PubMed:2732228). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase). Catalyzes the hydroxylation of carbon-hydrogen bonds (PubMed:10681376, PubMed:11093772, PubMed:12865317, PubMed:2732228). Exhibits high catalytic activity for the formation of catechol estrogens from 17beta-estradiol (E2) and estrone (E1), namely 2-hydroxy E1 and E2 (PubMed:12865317). Catalyzes 6beta-hydroxylation of the steroid hormones testosterone, progesterone, and androstenedione (PubMed:2732228). Catalyzes the oxidative conversion of all-trans-retinol to all-trans-retinal, a rate-limiting step for the biosynthesis of all-trans-retinoic acid (atRA) (PubMed:10681376). Further metabolizes all trans-retinoic acid (atRA) to 4-hydroxyretinoate and may play a role in hepatic atRA clearance (PubMed:11093772). Also involved in the oxidative metabolism of xenobiotics, including calcium channel blocking drug nifedipine and immunosuppressive drug cyclosporine (PubMed:2732228)
Specific Function
aromatase activity
Gene Name
CYP3A5
Uniprot ID
P20815
Uniprot Name
Cytochrome P450 3A5
Molecular Weight
57108.065 Da
References
  1. Dvorak Z, Pavek P: Regulation of drug-metabolizing cytochrome P450 enzymes by glucocorticoids. Drug Metab Rev. 2010 Nov;42(4):621-35. doi: 10.3109/03602532.2010.484462. [Article]

Carriers

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Binder
General Function
Major transport protein for glucocorticoids and progestins in the blood of almost all vertebrate species
Specific Function
serine-type endopeptidase inhibitor activity
Gene Name
SERPINA6
Uniprot ID
P08185
Uniprot Name
Corticosteroid-binding globulin
Molecular Weight
45140.49 Da
References
  1. Gardill BR, Vogl MR, Lin HY, Hammond GL, Muller YA: Corticosteroid-binding globulin: structure-function implications from species differences. PLoS One. 2012;7(12):e52759. doi: 10.1371/journal.pone.0052759. Epub 2012 Dec 26. [Article]
  2. SLAUNWHITE WR Jr, SANDBERG AA: Transcortin: a corticosteroid-binding protein of plasma. J Clin Invest. 1959 Feb;38(2):384-91. doi: 10.1172/JCI103812. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Binder
General Function
Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transporter in plasma, typically binds about 80% of all plasma zinc (PubMed:19021548). Major calcium and magnesium transporter in plasma, binds approximately 45% of circulating calcium and magnesium in plasma (By similarity). Potentially has more than two calcium-binding sites and might additionally bind calcium in a non-specific manner (By similarity). The shared binding site between zinc and calcium at residue Asp-273 suggests a crosstalk between zinc and calcium transport in the blood (By similarity). The rank order of affinity is zinc > calcium > magnesium (By similarity). Binds to the bacterial siderophore enterobactin and inhibits enterobactin-mediated iron uptake of E.coli from ferric transferrin, and may thereby limit the utilization of iron and growth of enteric bacteria such as E.coli (PubMed:6234017). Does not prevent iron uptake by the bacterial siderophore aerobactin (PubMed:6234017)
Specific Function
antioxidant activity
Gene Name
ALB
Uniprot ID
P02768
Uniprot Name
Albumin
Molecular Weight
69365.94 Da
References
  1. Czock D, Keller F, Rasche FM, Haussler U: Pharmacokinetics and pharmacodynamics of systemically administered glucocorticoids. Clin Pharmacokinet. 2005;44(1):61-98. doi: 10.2165/00003088-200544010-00003. [Article]

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Na(+)-independent transporter that mediates the cellular uptake of a broad range of organic anions such as the endogenous bile salts cholate and deoxycholate, either in their unconjugated or conjugated forms (taurocholate and glycocholate), at the plasmam membrane (PubMed:19129463, PubMed:7557095). Responsible for intestinal absorption of bile acids (By similarity). Transports dehydroepiandrosterone 3-sulfate (DHEAS), a major circulating steroid secreted by the adrenal cortex, as well as estrone 3-sulfate and 17beta-estradiol 17-O-(beta-D-glucuronate) (PubMed:11159893, PubMed:12568656, PubMed:19129463, PubMed:23918469, PubMed:25560245, PubMed:9539145). Mediates apical uptake of all-trans-retinol (atROL) across human retinal pigment epithelium, which is essential to maintaining the integrity of the visual cycle and thus vision (PubMed:25560245). Involved in the uptake of clinically used drugs (PubMed:17301733, PubMed:20686826, PubMed:27777271). Capable of thyroid hormone transport (both T3 or 3,3',5'-triiodo-L-thyronine, and T4 or L-tyroxine) (PubMed:19129463, PubMed:20358049). Also transports prostaglandin E2 (PubMed:19129463). Plays roles in blood-brain and -cerebrospinal fluid barrier transport of organic anions and signal mediators, and in hormone uptake by neural cells (By similarity). May also play a role in the reuptake of neuropeptides such as substance P/TAC1 and vasoactive intestinal peptide/VIP released from retinal neurons (PubMed:25132355). May play an important role in plasma and tissue distribution of the structurally diverse chemotherapeutic drugs methotrexate and paclitaxel (PubMed:23243220). Shows a pH-sensitive substrate specificity which may be ascribed to the protonation state of the binding site and leads to a stimulation of substrate transport in an acidic microenvironment (PubMed:19129463). Hydrogencarbonate/HCO3(-) acts as the probable counteranion that exchanges for organic anions (PubMed:19129463). May contribute to regulate the transport of organic compounds in testis across the blood-testis-barrier (Probable)
Specific Function
bile acid transmembrane transporter activity
Gene Name
SLCO1A2
Uniprot ID
P46721
Uniprot Name
Solute carrier organic anion transporter family member 1A2
Molecular Weight
74144.105 Da
References
  1. 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. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inducer
General Function
Translocates drugs and phospholipids across the membrane (PubMed:2897240, PubMed:35970996, PubMed:8898203, PubMed:9038218). Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of phosphatidylcholine, phosphatidylethanolamine, beta-D-glucosylceramides and sphingomyelins (PubMed:8898203). Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells (PubMed:2897240, PubMed:35970996, PubMed:9038218)
Specific Function
ABC-type xenobiotic transporter activity
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
ATP-dependent translocase ABCB1
Molecular Weight
141477.255 Da
References
  1. Yates CR, Chang C, Kearbey JD, Yasuda K, Schuetz EG, Miller DD, Dalton JT, Swaan PW: Structural determinants of P-glycoprotein-mediated transport of glucocorticoids. Pharm Res. 2003 Nov;20(11):1794-803. [Article]
  2. Matoulkova P, Pavek P, Maly J, Vlcek J: Cytochrome P450 enzyme regulation by glucocorticoids and consequences in terms of drug interaction. Expert Opin Drug Metab Toxicol. 2014 Mar;10(3):425-35. doi: 10.1517/17425255.2014.878703. Epub 2014 Jan 23. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Functions as an organic anion/dicarboxylate exchanger that couples organic anion uptake indirectly to the sodium gradient (PubMed:14586168, PubMed:15644426, PubMed:15846473, PubMed:16455804, PubMed:31553721). Transports organic anions such as estrone 3-sulfate (E1S) and urate in exchange for dicarboxylates such as glutarate or ketoglutarate (2-oxoglutarate) (PubMed:14586168, PubMed:15846473, PubMed:15864504, PubMed:22108572, PubMed:23832370). Plays an important role in the excretion of endogenous and exogenous organic anions, especially from the kidney and the brain (PubMed:11306713, PubMed:14586168, PubMed:15846473). E1S transport is pH- and chloride-dependent and may also involve E1S/cGMP exchange (PubMed:26377792). Responsible for the transport of prostaglandin E2 (PGE2) and prostaglandin F2(alpha) (PGF2(alpha)) in the basolateral side of the renal tubule (PubMed:11907186). Involved in the transport of neuroactive tryptophan metabolites kynurenate and xanthurenate (PubMed:22108572, PubMed:23832370). Functions as a biopterin transporters involved in the uptake and the secretion of coenzymes tetrahydrobiopterin (BH4), dihydrobiopterin (BH2) and sepiapterin to urine, thereby determining baseline levels of blood biopterins (PubMed:28534121). May be involved in the basolateral transport of steviol, a metabolite of the popular sugar substitute stevioside (PubMed:15644426). May participate in the detoxification/ renal excretion of drugs and xenobiotics, such as the histamine H(2)-receptor antagonists fexofenadine and cimetidine, the antibiotic benzylpenicillin (PCG), the anionic herbicide 2,4-dichloro-phenoxyacetate (2,4-D), the diagnostic agent p-aminohippurate (PAH), the antiviral acyclovir (ACV), and the mycotoxin ochratoxin (OTA), by transporting these exogenous organic anions across the cell membrane in exchange for dicarboxylates such as 2-oxoglutarate (PubMed:11669456, PubMed:15846473, PubMed:16455804). Contributes to the renal uptake of potent uremic toxins (indoxyl sulfate (IS), indole acetate (IA), hippurate/N-benzoylglycine (HA) and 3-carboxy-4-methyl-5-propyl-2-furanpropionate (CMPF)), pravastatin, PCG, E1S and dehydroepiandrosterone sulfate (DHEAS), and is partly involved in the renal uptake of temocaprilat (an angiotensin-converting enzyme (ACE) inhibitor) (PubMed:14675047). May contribute to the release of cortisol in the adrenals (PubMed:15864504). Involved in one of the detoxification systems on the choroid plexus (CP), removes substrates such as E1S or taurocholate (TC), PCG, 2,4-D and PAH, from the cerebrospinal fluid (CSF) to the blood for eventual excretion in urine and bile (By similarity). Also contributes to the uptake of several other organic compounds such as the prostanoids prostaglandin E(2) and prostaglandin F(2-alpha), L-carnitine, and the therapeutic drugs allopurinol, 6-mercaptopurine (6-MP) and 5-fluorouracil (5-FU) (By similarity). Mediates the transport of PAH, PCG, and the statins pravastatin and pitavastatin, from the cerebrum into the blood circulation across the blood-brain barrier (BBB). In summary, plays a role in the efflux of drugs and xenobiotics, helping reduce their undesired toxicological effects on the body (By similarity)
Specific Function
organic anion transmembrane transporter activity
Gene Name
SLC22A8
Uniprot ID
Q8TCC7
Uniprot Name
Organic anion transporter 3
Molecular Weight
59855.585 Da
References
  1. VanWert AL, Gionfriddo MR, Sweet DH: Organic anion transporters: discovery, pharmacology, regulation and roles in pathophysiology. Biopharm Drug Dispos. 2010 Jan;31(1):1-71. doi: 10.1002/bdd.693. [Article]

Drug created at July 06, 2007 20:32 / Updated at October 30, 2024 19:34