Identification

Name
Hydrocortamate
Accession Number
DB00769  (APRD01018)
Type
Small Molecule
Groups
Approved
Description

Hydrocortamate is a synthetic glucocorticoid used for its anti-inflammatory or immunosuppressive properties to treat inflammation due to corticosteroid-responsive dermatoses. Glucocorticoids are a class of steroid hormones characterised by an ability to bind with the cortisol receptor and trigger a variety of important cardiovascular, metabolic, immunologic and homeostatic effects.

Structure
Thumb
Synonyms
  • 17-Hydroxycorticosterone, 21-(diethylamino)acetate
  • Hidrocortamato
  • Hydrocortamatum
Product Ingredients
IngredientUNIICASInChI Key
Hydrocortamate Hydrochloride9QM8U7R83W125-03-1AKQNAIYKSALPKV-OYHXESGYSA-N
International/Other Brands
Etacort (Angelini) / Magnacort (Pfizer) / Ulcort / Ulcort top
Categories
UNII
Y3N00BK5WK
CAS number
76-47-1
Weight
Average: 475.6175
Monoisotopic: 475.293388049
Chemical Formula
C27H41NO6
InChI Key
FWFVLWGEFDIZMJ-FOMYWIRZSA-N
InChI
InChI=1S/C27H41NO6/c1-5-28(6-2)15-23(32)34-16-22(31)27(33)12-10-20-19-8-7-17-13-18(29)9-11-25(17,3)24(19)21(30)14-26(20,27)4/h13,19-21,24,30,33H,5-12,14-16H2,1-4H3/t19-,20-,21-,24+,25-,26-,27-/m0/s1
IUPAC Name
2-[(1S,2R,10S,11S,14R,15S,17S)-14,17-dihydroxy-2,15-dimethyl-5-oxotetracyclo[8.7.0.0²,⁷.0¹¹,¹⁵]heptadec-6-en-14-yl]-2-oxoethyl 2-(diethylamino)acetate
SMILES
[H][[email protected]@]12CC[[email protected]](O)(C(=O)COC(=O)CN(CC)CC)[[email protected]@]1(C)C[[email protected]](O)[[email protected]@]1([H])[[email protected]@]2([H])CCC2=CC(=O)CC[[email protected]]12C

Pharmacology

Indication

Used topically as an antiinflammatory in the treatment of steroid-responsive dermatoses

Structured Indications
Not Available
Pharmacodynamics

Hydrocortamate is a synthetic glucocorticoid used for its anti-inflammatory or immunosuppressive properties to treat inflammation due to corticosteroid-responsive dermatoses. Glucocorticoids are a class of steroid hormones characterised by an ability to bind with the cortisol receptor and trigger a variety of important cardiovascular, metabolic, immunologic and homeostatic effects. Glucocorticoids are distinguished from mineralocorticoids and sex steroids by having different receptors, target cells, and effects. Technically, the term corticosteroid refers to both glucocorticoids and mineralocorticoids, but is often used as a synonym for glucocorticoid. Glucocorticoids suppress cell-mediated immunity. They act by inhibiting genes that code for the cytokines IL-1, IL-2, IL-3, IL-4, IL-5, IL-6, IL-8 and TNF-alpha, the most important of which is the IL-2. Reduced cytokine production limits T cell proliferation. Glucocorticoids also suppress humoral immunity, causing B cells to express lower amounts of IL-2 and IL-2 receptors. This diminishes both B cell clonal expansion and antibody synthesis. The diminished amounts of IL-2 also leads to fewer T lymphocyte cells being activated.

Mechanism of action

Hydrocortamate binds to the cytosolic glucocorticoid receptor. After binding the receptor the newly formed receptor-ligand complex translocates itself into the cell nucleus, where it binds to many glucocorticoid response elements (GRE) in the promoter region of the target genes. The DNA bound receptor then interacts with basic transcription factors, causing the increase in expression of specific target genes. The anti-inflammatory actions of corticosteroids are thought to involve lipocortins, phospholipase A2 inhibitory proteins which, through inhibition arachidonic acid, control the biosynthesis of prostaglandins and leukotrienes. The immune system is suppressed by corticosteroids due to a decrease in the function of the lymphatic system, a reduction in immunoglobulin and complement concentrations, the precipitation of lymphocytopenia, and interference with antigen-antibody binding.

TargetActionsOrganism
AGlucocorticoid receptor
agonist
Human
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism

Primarily hepatic via CYP3A4

Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity

Side effects include burning, itching, irritation, dryness, folliculitis, hypertrichosis, acneiform eruptions, hypopigmentation, perioral dermatitis, allergic contact dermatitis, maceration of the skin, secondary infection, skin atrophy, striae, miliaria.

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

Interactions

Drug Interactions
DrugInteractionDrug group
AripiprazoleThe serum concentration of Aripiprazole can be decreased when it is combined with Hydrocortamate.Approved, Investigational
SaxagliptinThe serum concentration of Saxagliptin can be decreased when it is combined with Hydrocortamate.Approved
Food Interactions
Not Available

References

Synthesis Reference

British Patent 879,208; October 4, 1961.

General References
Not Available
External Links
Human Metabolome Database
HMDB14907
PubChem Compound
84088
PubChem Substance
46509076
ChemSpider
75860
ChEBI
50851
ChEMBL
CHEMBL1201263
Therapeutic Targets Database
DAP001187
PharmGKB
PA164745515
ATC Codes
Not Available
AHFS Codes
Not Available
PDB Entries
Not Available
FDA label
Not Available
MSDS
Not Available

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
  • Pfizer laboratories div pfizer inc
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)162-163British Patent 879,208; October 4, 1961.
logP1.2Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0855 mg/mLALOGPS
logP2.82ALOGPS
logP2.32ChemAxon
logS-3.8ALOGPS
pKa (Strongest Acidic)12.61ChemAxon
pKa (Strongest Basic)6.43ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area104.14 Å2ChemAxon
Rotatable Bond Count8ChemAxon
Refractivity129.48 m3·mol-1ChemAxon
Polarizability53.29 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9681
Blood Brain Barrier+0.9382
Caco-2 permeable-0.6251
P-glycoprotein substrateSubstrate0.8848
P-glycoprotein inhibitor IInhibitor0.8649
P-glycoprotein inhibitor IIInhibitor0.7043
Renal organic cation transporterNon-inhibitor0.7574
CYP450 2C9 substrateNon-substrate0.8889
CYP450 2D6 substrateNon-substrate0.8473
CYP450 3A4 substrateSubstrate0.7533
CYP450 1A2 substrateNon-inhibitor0.913
CYP450 2C9 inhibitorNon-inhibitor0.8642
CYP450 2D6 inhibitorNon-inhibitor0.7771
CYP450 2C19 inhibitorNon-inhibitor0.8833
CYP450 3A4 inhibitorNon-inhibitor0.6776
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8749
Ames testNon AMES toxic0.8229
CarcinogenicityNon-carcinogens0.9077
BiodegradationNot ready biodegradable0.9903
Rat acute toxicity2.9454 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8902
hERG inhibition (predictor II)Non-inhibitor0.5096
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 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 / 11-beta-hydroxysteroids / 17-hydroxysteroids / 3-oxo delta-4-steroids / Delta-4-steroids / Alpha amino acid esters / Alpha-acyloxy ketones / Cyclohexenones / Tertiary alcohols / Alpha-hydroxy ketones
show 8 more
Substituents
Progestogin-skeleton / 20-oxosteroid / 3-oxo-delta-4-steroid / Oxosteroid / Hydroxysteroid / 3-oxosteroid / 11-beta-hydroxysteroid / 11-hydroxysteroid / 17-hydroxysteroid / Delta-4-steroid
show 27 more
Molecular Framework
Aliphatic homopolycyclic compounds
External Descriptors
3-oxo steroid, glycinyl ester, 11beta-hydroxy steroid, 17alpha-hydroxy steroid, glucocorticoid (CHEBI:50851)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
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. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inducer
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. El-Sankary W, Bombail V, Gibson GG, Plant N: Glucocorticoid-mediated induction of CYP3A4 is decreased by disruption of a protein: DNA interaction distinct from the pregnane X receptor response element. Drug Metab Dispos. 2002 Sep;30(9):1029-34. [PubMed:12167569]

Drug created on June 13, 2005 07:24 / Updated on October 02, 2017 04:44