DrugBank: Hydrocortamate (DB00769)

targets (1) enzymes (1)

Identification

Name

Hydrocortamate

Accession Number

DB00769 (APRD01018)

Type

small molecule

Groups

approved

Description

Structure

Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure

Synonyms

Not Available

Salts

Not Available

Brand names

Name	Company
Hydrocortamate Hydrochloride
Magnacort
Ulcort

Brand mixtures

Not Available

Categories

Immunosuppressive Agents
Glucocorticoids
Corticosteroid
Anti-inflammatory Agents, Steroidal

CAS number

76-47-1

Weight

Average: 475.6175
Monoisotopic: 475.293388049

Chemical Formula

C₂₇H₄₁NO₆

InChI Key

InChIKey=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

Plain Text

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

Plain Text

Mass Spec

Not Available

Taxonomy

Kingdom

Not Available

Classes

Not Available

Substructures

Not Available

Pharmacology

Indication

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

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.

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

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

Property	Value	Source
melting point	162.5 °C	PhysProp
logP	1.2	Not Available

Predicted Properties

Property	Value	Source
water solubility	8.55e-02 g/l	ALOGPS
logP	2.82	ALOGPS
logP	2.32	ChemAxon
logS	-3.8	ALOGPS
pKa (strongest acidic)	12.61	ChemAxon
pKa (strongest basic)	6.43	ChemAxon
physiological charge	0	ChemAxon
hydrogen acceptor count	6	ChemAxon
hydrogen donor count	2	ChemAxon
polar surface area	104.14	ChemAxon
rotatable bond count	8	ChemAxon
refractivity	129.48	ChemAxon
polarizability	53.29	ChemAxon

References

Synthesis Reference

Not Available

General Reference

Not Available

External Links

Resource	Link
ChEBI	50851
ChEMBL	50851
Therapeutic Targets Database	DAP001187
PharmGKB	PA164745515

ATC Codes

A07EA04
C05AA05
D07AC01

AHFS Codes

Not Available

PDB Entries

Not Available

FDA label

Not Available

MSDS

Not Available

Interactions

Drug Interactions

Not Available

Food Interactions

Not Available

Targets
1. Glucocorticoid receptor Pharmacological action: yes Actions: agonist Receptor for glucocorticoids (GC). Has a dual mode of action:as a transcription factor that binds to glucocorticoid response elements (GRE) 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 growth hormone (GH) stimulation and could reveal an essential role of hepatic GR in the control of body growth Organism class: human UniProt ID: P04150 Gene: NR3C1 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed 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

Targets

1. Glucocorticoid receptor

Pharmacological action: yes
Actions: agonist

Receptor for glucocorticoids (GC). Has a dual mode of action:as a transcription factor that binds to glucocorticoid response elements (GRE) 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 growth hormone (GH) stimulation and could reveal an essential role of hepatic GR in the control of body growth

Organism class: human
UniProt ID: P04150 Link_out

Gene: NR3C1 Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
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 Actions: inducer 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 xenobiotics. The enzyme also hydroxylates etoposide UniProt ID: P08684 Gene: CYP3A4 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: 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

Enzymes

1. Cytochrome P450 3A4

Actions: inducer

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 xenobiotics. The enzyme also hydroxylates etoposide

UniProt ID: P08684 Link_out

Gene: CYP3A4
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

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

Comments

Drug created on June 13, 2005 07:24 / Updated on February 08, 2013 16:19