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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
SynonymLanguageCode
17-Hydroxycorticosterone, 21-(diethylamino)acetateNot AvailableNot Available
HidrocortamatoNot AvailableNot Available
HydrocortamatumNot AvailableNot 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
CAS number76-47-1
WeightAverage: 475.6175
Monoisotopic: 475.293388049
Chemical FormulaC27H41NO6
InChI KeyFWFVLWGEFDIZMJ-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[C@H](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.
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 substrateNon-inhibitor0.8642
CYP450 2D6 substrateNon-inhibitor0.7771
CYP450 2C19 substrateNon-inhibitor0.8833
CYP450 3A4 substrateNon-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
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 ReferenceNot Available
External Links
ATC CodesNot Available
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug Interactions
Drug
AldesleukinMay diminish the antineoplastic effect of Aldesleukin. Exceptions: Beclomethasone (Nasal); Budesonide (Nasal); Ciclesonide (Nasal); Desonide; Dexamethasone (Ophthalmic); Difluprednate; Flunisolide (Nasal); Fluocinolone (Ophthalmic); Fluticasone (Nasal); Loteprednol; Mometasone (Nasal); PrednisoLONE (Ophthalmic); Triamcinolone (Nasal); Triamcinolone (Ophthalmic).
DeferasiroxMay enhance the adverse/toxic effect of Deferasirox. Specifically, the risk for GI ulceration/irritation or GI bleeding may be increased. Exceptions: Beclomethasone (Nasal); Budesonide (Nasal); Ciclesonide (Nasal); Desonide; Dexamethasone (Ophthalmic); Difluprednate; Flunisolide (Nasal); Fluocinolone (Ophthalmic); Fluticasone (Nasal); Loteprednol; Mometasone (Nasal); PrednisoLONE (Ophthalmic); Triamcinolone (Nasal); Triamcinolone (Ophthalmic).
HyaluronidaseMay diminish the therapeutic effect of Hyaluronidase.
TelaprevirMay decrease the serum concentration of Telaprevir. Telaprevir may increase the serum concentration of Corticosteroids.
Food InteractionsNot Available

Targets

1. Glucocorticoid receptor

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: agonist

Components

Name UniProt ID Details
Glucocorticoid receptor P04150 Details

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
  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

Enzymes

1. Cytochrome P450 3A4

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inducer

Components

Name UniProt ID Details
Cytochrome P450 3A4 P08684 Details

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

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Drug created on June 13, 2005 07:24 / Updated on April 29, 2014 10:32