DT-Web

DB00547 - Desoximetasone


Identification
Name Desoximetasone
Accession Number DB00547 (APRD00910)
Type small molecule
Description A topical anti-inflammatory glucocorticoid used in dermatoses, skin allergies, psoriasis, etc. [PubChem]
Structure
MOL SDF PDB SMILES InChI
Categories (*)
Molecular Weight 376.4617
Groups approved
Monoisotopic Weight 376.204987621
Pharmacology
Indication For the relief of the inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses.
Mechanism of action The precise mechanism of the antiinflammatory activity of topical steroids in the treatment of steroid-responsive dermatoses, in general, is uncertain. However, corticosteroids are thought to act by the induction of phospholipase A2 inhibitory proteins, collectively called lipocortins. This is achieved first by the drug binding to the glucocorticoid receptors which then translocates into the nucleus and binds to DNA causing various activations and repressions of genes. It is postulated that these proteins control the biosynthesis of potent mediators of inflammation such as prostaglandins and leukotrienes by inhibiting the release of their common precursor arachidonic acid. Arachidonic acid is released from membrane phospholipids by phospholipase A2.
Absorption Topical corticosteroids can be absorbed from intact healthy skin. The extent of percutaneous absorption of topical corticosteroids is determined by many factors, including the vehicle and the integrity of the epidermal barrier. Occlusion, inflammation and/or other disease processes in the skin may also increase percutaneous absorption.
Protein binding Bound to plasma proteins in varying degrees.
Biotransformation Metabolized, primarily in the liver, and then excreted by the kidneys.
Route of elimination Corticosteroids are bound to plasma proteins in varying degrees, are metabolized primarily in the liver and excreted by the kidneys. Some of the topical corticosteroids and their metabolites are also excreted into the bile.Pharmacokinetic studies in men with Desoximetasone Cream USP, 0.25% with tagged desoximetasone showed a total of 5.2% ? 2.9% excretion in urine (4.1% ? 2.3%) and feces (1.1% ? 0.6%)
Toxicity Topically applied desoximetasone can be absorbed in sufficient amounts to produce systemic effects. Symptoms of overdose include thinning of skin and suppression of adrenal cortex (decreased ability to respond to stress).
Affected organisms
  • Humans and other mammals
Interactions
Drug Interactions Not Available
Food Interactions Not Available

Targets


Glucocorticoid receptor
Name Glucocorticoid receptor
Gene Name NR3C1
Pharmacological action yes
Actions agonist
References
  • Lange K, Kleuser B, Gysler A, Bader M, Maia C, Scheidereit C, Korting HC, Schafer-Korting M: Cutaneous inflammation and proliferation in vitro: differential effects and mode of action of topical glucocorticoids. Skin Pharmacol Appl Skin Physiol. 2000 Mar-Apr;13(2):93-103. - Pubmed
  • Grossman R, Yehuda R, Golier J, McEwen B, Harvey P, Maria NS: Cognitive effects of intravenous hydrocortisone in subjects with PTSD and healthy control subjects. Ann N Y Acad Sci. 2006 Jul;1071:410-21. - Pubmed
  • Rautanen A, Eriksson JG, Kere J, Andersson S, Osmond C, Tienari P, Sairanen H, Barker DJ, Phillips DI, Forsen T, Kajantie E: Associations of body size at birth with late-life cortisol concentrations and glucose tolerance are modified by haplotypes of the glucocorticoid receptor gene. J Clin Endocrinol Metab. 2006 Nov;91(11):4544-51. Epub 2006 Aug 8. - Pubmed
  • Hammer F, Stewart PM: Cortisol metabolism in hypertension. Best Pract Res Clin Endocrinol Metab. 2006 Sep;20(3):337-53. - Pubmed
  • Shaw JR, Gabor K, Hand E, Lankowski A, Durant L, Thibodeau R, Stanton CR, Barnaby R, Coutermarsh B, Karlson KH, Sato JD, Hamilton JW, Stanton BA: Role of glucocorticoid receptor in acclimation of killifish (Fundulus heteroclitus) to seawater and effects of arsenic. Am J Physiol Regul Integr Comp Physiol. 2007 Feb;292(2):R1052-60. Epub 2006 Oct 12. - Pubmed
  • Sher L: Combined dexamethasone suppression-corticotropin-releasing hormone stimulation test in studies of depression, alcoholism, and suicidal behavior. ScientificWorldJournal. 2006 Oct 31;6:1398-404. - Pubmed
DTHybrid score 0.778

Predictions


Id Partner name Gene Name Score
232 Corticosteroid-binding globulin SERPINA6 0.2409
4512 Cytochrome P450 3A4 CYP3A4 0.0775
469 Annexin A1 ANXA1 0.0385
1588 Multidrug resistance protein 1 ABCB1 0.0326
614 Progesterone receptor PGR 0.0223
737 Mineralocorticoid receptor NR3C2 0.0198
723 Cytosolic phospholipase A2 PLA2G4A 0.0179
146 Androgen receptor AR 0.0161
4118 Cytochrome P450 3A5 CYP3A5 0.0143
381 Prolactin receptor PRLR 0.0142
4924 Cytochrome P450 2C8 CYP2C8 0.0122
756 Sex hormone-binding globulin SHBG 0.0114
6139 Solute carrier organic anion transporter family member 1A2 SLCO1A2 0.0112
2751 Holliday junction ATP-dependent DNA helicase ruvB ruvB 0.0105
4755 Holliday junction ATP-dependent DNA helicase ruvB ruvB 0.0105
4615 Chain A, Red Copper Protein Nitrosocyanin NE0143 0.0093
6024 Cytochrome P450 1A1 CYP1A1 0.0084
3811 Cytochrome P450 19A1 CYP19A1 0.0083
6107 Cytochrome P450 3A7 CYP3A7 0.008
1758 GTPase HRas HRAS 0.0068
4119 Cytochrome P450 2D6 CYP2D6 0.0063
4604 Liver carboxylesterase 1 CES1 0.0061
4200 Cytochrome P450 1A2 CYP1A2 0.0061
6500 Phospholipase A2 PLA2G1B 0.006
136 Estrogen receptor ESR1 0.0052
3923 Cholinesterase BCHE 0.0049
5718 Cytochrome P450 2A6 CYP2A6 0.0048
364 Corticosteroid 11-beta-dehydrogenase isozyme 1 HSD11B1 0.0048
290 Prostaglandin G/H synthase 2 PTGS2 0.0048
2300 Lysozyme E 0.0047
3633 Lysozyme R 0.0047
5597 Lysozyme 17 0.0047
6023 Cytochrome P450 11B2, mitochondrial CYP11B2 0.0035
6016 Cytochrome P450 2C19 CYP2C19 0.0034
862 Multidrug resistance-associated protein 1 ABCC1 0.0031
587 Serum albumin ALB 0.003
805 Cytochrome P450 11B1, mitochondrial CYP11B1 0.0028
1732 ATP-binding cassette sub-family G member 2 ABCG2 0.0028
84 Nuclear receptor 0B1 NR0B1 0.0023
380 Cytochrome P450 17A1 CYP17A1 0.0017
6031 Cytochrome P450 3A43 CYP3A43 0.0014
468 Cytochrome P450 4A11 CYP4A11 0.0014
6017 Cholesterol side-chain cleavage enzyme, mitochondrial CYP11A1 0.0013
1898 Cytochrome P450 1B1 CYP1B1 0.0011
776 Bile salt export pump ABCB11 0.0011
7 Nitric oxide synthase, inducible NOS2 0.0011
1735 Canalicular multispecific organic anion transporter 1 ABCC2 0.0009
6030 Cytochrome P450 2B6 CYP2B6 0.0008
6013 Cytochrome P450 2E1 CYP2E1 0.0008
4757 Cytochrome P450 2C9 CYP2C9 0.0007
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