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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
Salts
Name/CAS Structure Properties
Hydrocortamate Hydrochloride
Thumb
  • InChI Key: AKQNAIYKSALPKV-OYHXESGYSA-N
  • Monoisotopic Mass: 511.270065788
  • Average Mass: 512.078
DBSALT000686
Brand names
NameCompany
EtacortAngelini
MagnacortPfizer
UlcortNot Available
Ulcort topNot Available
Brand mixturesNot Available
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[8.7.0.0^{2,7}.0^{11,15}]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
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassLipids
ClassSteroids and Steroid Derivatives
SubclassGluco/mineralocorticoids, Progestogins and Derivatives
Direct parentGluco/mineralocorticoids, Progestogins and Derivatives
Alternative parentsHydroxysteroids; Ketosteroids; Alpha Amino Acid Esters; Cyclohexanols; Tertiary Alcohols; Ketones; Carboxylic Acid Esters; Cyclic Alcohols and Derivatives; Tertiary Amines; Ethers; Enolates; Polyamines; Aldehydes
Substituents3-keto-steroid; 20-keto-steroid; 17-hydroxy-steroid; 11-hydroxy-steroid; alpha-amino acid ester; alpha-amino acid or derivative; cyclohexanol; tertiary alcohol; cyclic alcohol; tertiary amine; carboxylic acid ester; secondary alcohol; ketone; enolate; carboxylic acid derivative; ether; polyamine; alcohol; amine; carbonyl group; organonitrogen compound; aldehyde
Classification descriptionThis compound belongs to the gluco/mineralocorticoids, progestogins and derivatives. These are steroids whose structure is based on an hydroxylated prostane moiety.
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
Property Value Probability
Human Intestinal Absorption + 0.9681
Blood Brain Barrier + 0.9382
Caco-2 permeable - 0.6251
P-glycoprotein substrate Substrate 0.8848
P-glycoprotein inhibitor I Inhibitor 0.8649
P-glycoprotein inhibitor II Inhibitor 0.7043
Renal organic cation transporter Non-inhibitor 0.7574
CYP450 2C9 substrate Non-substrate 0.8889
CYP450 2D6 substrate Non-substrate 0.8473
CYP450 3A4 substrate Substrate 0.7533
CYP450 1A2 substrate Non-inhibitor 0.913
CYP450 2C9 substrate Non-inhibitor 0.8642
CYP450 2D6 substrate Non-inhibitor 0.7771
CYP450 2C19 substrate Non-inhibitor 0.8833
CYP450 3A4 substrate Non-inhibitor 0.6776
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.8749
Ames test Non AMES toxic 0.8229
Carcinogenicity Non-carcinogens 0.9077
Biodegradation Not ready biodegradable 0.9903
Rat acute toxicity 2.9454 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.8902
hERG inhibition (predictor II) Non-inhibitor 0.5096
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 solubility8.55e-02 g/lALOGPS
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 area104.14ChemAxon
rotatable bond count8ChemAxon
refractivity129.48ChemAxon
polarizability53.29ChemAxon
number of rings4ChemAxon
bioavailability1ChemAxon
rule of fiveYesChemAxon
Ghose filterNoChemAxon
Veber's ruleNoChemAxon
MDDR-like ruleYesChemAxon
Spectra
SpectraNot Available
References
Synthesis Reference

British Patent 879,208; October 4, 1961.

General ReferenceNot Available
External Links
ResourceLink
ChEBI50851
ChEMBL
Therapeutic Targets DatabaseDAP001187
PharmGKBPA164745515
ATC CodesNot Available
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug InteractionsNot Available
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