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Identification
NameHydrocortamate
Accession NumberDB00769  (APRD01018)
TypeSmall Molecule
GroupsApproved
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
External Identifiers Not Available
Prescription ProductsNot Available
Generic Prescription ProductsNot Available
Over the Counter ProductsNot Available
International Brands
NameCompany
EtacortAngelini
MagnacortPfizer
UlcortNot Available
Ulcort topNot Available
Brand mixturesNot Available
Salts
Name/CASStructureProperties
Hydrocortamate Hydrochloride
Thumb
  • InChI Key: AKQNAIYKSALPKV-OYHXESGYSA-N
  • Monoisotopic Mass: 511.270065788
  • Average Mass: 512.078
DBSALT000686
Categories
UNIIY3N00BK5WK
CAS number76-47-1
WeightAverage: 475.6175
Monoisotopic: 475.293388049
Chemical FormulaC27H41NO6
InChI KeyInChIKey=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][C@@]12CC[C@](O)(C(=O)COC(=O)CN(CC)CC)[C@@]1(C)C[[email protected]](O)[C@@]1([H])[C@@]2([H])CCC2=CC(=O)CC[C@]12C
Taxonomy
DescriptionThis 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.
KingdomOrganic compounds
Super ClassLipids and lipid-like molecules
ClassSteroids and steroid derivatives
Sub ClassPregnane steroids
Direct ParentGluco/mineralocorticoids, progestogins and derivatives
Alternative Parents
Substituents
  • Progestogin-skeleton
  • 20-oxosteroid
  • 17-hydroxysteroid
  • 11-hydroxysteroid
  • 11-beta-hydroxysteroid
  • Oxosteroid
  • Hydroxysteroid
  • 3-oxosteroid
  • 3-oxo-delta-4-steroid
  • Delta-4-steroid
  • Alpha-amino acid ester
  • Alpha-amino acid or derivatives
  • Alpha-acyloxy ketone
  • Tertiary alcohol
  • Cyclic alcohol
  • Alpha-hydroxy ketone
  • Cyclic ketone
  • Tertiary aliphatic amine
  • Tertiary amine
  • Secondary alcohol
  • Ketone
  • Carboxylic acid ester
  • Monocarboxylic acid or derivatives
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Amine
  • Alcohol
  • Aliphatic homopolycyclic compound
Molecular FrameworkAliphatic homopolycyclic compounds
External Descriptors
Pharmacology
IndicationUsed topically as an antiinflammatory in the treatment of steroid-responsive dermatoses
PharmacodynamicsHydrocortamate 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 actionHydrocortamate 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.
Related Articles
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNot Available
Metabolism

Primarily hepatic via CYP3A4

Route of eliminationNot Available
Half lifeNot Available
ClearanceNot Available
ToxicitySide 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
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
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 )
Pharmacoeconomics
Manufacturers
  • Pfizer laboratories div pfizer inc
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point162-163British 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 FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis Reference

British Patent 879,208; October 4, 1961.

General ReferencesNot Available
External Links
ATC CodesNot Available
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug Interactions
Drug
AldesleukinHydrocortamate may decrease the antineoplastic activities of Aldesleukin.
CeritinibHydrocortamate may increase the hyperglycemic activities of Ceritinib.
CorticorelinThe therapeutic efficacy of Corticorelin can be decreased when used in combination with Hydrocortamate.
DeferasiroxThe risk or severity of adverse effects can be increased when Hydrocortamate is combined with Deferasirox.
HyaluronidaseThe therapeutic efficacy of Hyaluronidase can be decreased when used in combination with Hydrocortamate.
Food InteractionsNot Available

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 modulator of other transcription factors. Affects inflammatory responses, cellular proliferation and differentiation in target tissues. Could act as a coactivator for STAT5-dependent transcription upon grow...
Gene Name:
NR3C1
Uniprot ID:
P04150
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 reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiot...
Gene Name:
CYP3A4
Uniprot ID:
P08684
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 ]
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Drug created on June 13, 2005 07:24 / Updated on April 29, 2014 10:32