Dexamethasone (T3D4982)

IdentificationTaxonomyBiological PropertiesPhysical PropertiesToxicity ProfileSpectraConcentrationsLinksReferencesGene RegulationTargets (7)XML
Targets (7)
Record Information
Version2.0
Creation Date2014-10-14 21:18:42 UTC
Update Date2014-12-24 20:27:01 UTC
Accession NumberT3D4982
Identification
Common NameDexamethasone
ClassSmall Molecule
DescriptionAn anti-inflammatory 9-fluoro-glucocorticoid. [PubChem]
Compound Type
  • Anti-Inflammatory Agent
  • Antiemetic
  • Antineoplastic Agent, Hormonal
  • Drug
  • Glucocorticoid
  • Metabolite
  • Synthetic Compound
Chemical Structure
Thumb
MOLSDFPDBSMILESInChI
Synonyms
Synonym
1-Dehydro-16alpha -methyl-9alpha -fluorohydrocortisone
1-Dehydro-16alpha-methyl-9alpha-fluorohydrocortisone
1-Dehydro-16α-methyl-9α-fluorohydrocortisone
16-alpha-Methyl-9-alpha-fluoro-1-dehydrocortisol
16-alpha-Methyl-9-alpha-fluoro-delta1-hydrocortisone
16-alpha-Methyl-9-alpha-fluoroprednisolone
16alpha -Methyl-9alpha -fluoro-1-dehydrocortisol
16alpha -Methyl-9alpha -fluoroprednisolone
16alpha-Methyl-9alpha-fluoro-1-dehydrocortisol
16alpha-Methyl-9alpha-fluoro-delta1-hydrocortisone
16alpha-Methyl-9alpha-fluoroprednisolone
16α-Methyl-9α-fluoro-1-dehydrocortisol
9-alpha-Fluoro-16-alpha-methylprednisolone
9-Fluoro-11,17,21-trihydroxy-16-methylpregna-1,4-diene-3,20-dione
9-Fluoro-11alpha -methylpregna-1,4-diene-3,20-dione
9-Fluoro-16-methylprednisolone
9A-FLUORO-16BETA-METHYLPREDNISOLONE
9alpha -Fluoro-16alpha -methylprednisolone
9alpha-fluoro-16alpha-methyl-Prednisolone
9alpha-Fluoro-16alpha-methylprednisolone
9α-Fluoro-16α-methylprednisolone
Aeroseb-D
Aeroseb-dex
Ak Dex Oph Otic Soln 0.1%
alpha -Fluoro-16-alpha -methylcortisol
Anaflogistico
Aphtasolon
Apo-dexamethasone
Auxiron
Azimycin (veterinary)
Azium
Azium (veterinary)
Baycadron
Bisu DS
Calonat
Corson
Corsone
Cortisumman
Decacortin
Decaderm
Decadron
Decagel
Decalix
Decasone
Decaspray
Dectancyl
Dekacort
delta1-9-alpha-Fluoro-16-alpha-methylcortisol
Delta1-9alpha-Fluoro-16alpha-methylcortisol
Deltafluorene
Dergramin
Desadrene
Desametasone
Desamethasone
Desameton
Deseronil
DEX
Dex-ide
DEXA
Dexa mamallet
Dexa-cortidelt
Dexa-cortisyl
Dexa-scheroson
Dexa-sine
Dexacidin
Dexacort
Dexacortal
Dexacortin
Dexadeltone
Dexafarma
Dexalona
Dexametasona
Dexametasone
Dexameth
Dexamethansone
Dexamethasone Acetate
Dexamethasone alcohol
Dexamethasone base
Dexamethasone intensol
Dexamethasone Sodium Phosphate
Dexamethasone-omega
Dexamethasonum
Dexamethazone
Dexapolcort
Dexapos
Dexaprol
Dexason
Dexasone
Dexasone 0.5mg
Dexasone 0.75mg
Dexasone 4mg
Dexasporin
Dexinolon
Dexinoral
Dexone
DEXONE 0.5
DEXONE 0.75
DEXONE 1.5
DEXONE 4
Dextelan
Dezone
Dinormon
DXM
DXMS
Fluormethylprednisolone
Fortecortin
Gammacorten
Hexadecadrol
Hexadrol
Hexadrol elixir
HL-dex
Isopto-dex
Lokalison f
Loverine
Luxazone
Maxidex
Maxidex Ont 0.1%
Maxidex Sus 0.1%
Maxitrol
Mediamethasone
Methylfluorprednisolone
Mexidex
Mymethasone
Naquasone (veterinary)
Neomycin and polymyxin b sulfates and dexamethasone
Neomycin and polymyxin b sulphates and dexamethasone
NSC 34521
Ocu-trol
Oradexon
OZURDEX
Pet derm III
PHL-dexamethasone
Pms Dexamethasone Elixir 0.5mg/5ml
PMS-dexamethasone
Policort
Prednisolon f
Prednisolone f
Prodex
Sandoz dexamethasone
SK-dexamethasone
Spoloven
Sunia sol D
Superprednol
Tobradex
Tobramycin and dexamethasone
Tresaderm (veterinary)
Turbinaire
Visumetazone
Chemical FormulaC22H29FO5
Average Molecular Mass392.461 g/mol
Monoisotopic Mass392.200 g/mol
CAS Registry Number50-02-2
IUPAC Name(1R,2S,10S,11S,13R,14R,15S,17S)-1-fluoro-14,17-dihydroxy-14-(2-hydroxyacetyl)-2,13,15-trimethyltetracyclo[8.7.0.0²,⁷.0¹¹,¹⁵]heptadeca-3,6-dien-5-one
Traditional Namedexamethasone
SMILES[H][C@@]1(C)C[C@@]2([H])[C@]3([H])CCC4=CC(=O)C=C[C@]4(C)[C@@]3(F)[C@@]([H])(O)C[C@]2(C)[C@@]1(O)C(=O)CO
InChI IdentifierInChI=1S/C22H29FO5/c1-12-8-16-15-5-4-13-9-14(25)6-7-19(13,2)21(15,23)17(26)10-20(16,3)22(12,28)18(27)11-24/h6-7,9,12,15-17,24,26,28H,4-5,8,10-11H2,1-3H3/t12-,15+,16+,17+,19+,20+,21+,22+/m1/s1
InChI KeyInChIKey=UREBDLICKHMUKA-CXSFZGCWSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as 21-hydroxysteroids. These are steroids carrying a hydroxyl group at the 21-position of the steroid backbone.
KingdomOrganic compounds
Super ClassLipids and lipid-like molecules
ClassSteroids and steroid derivatives
Sub ClassHydroxysteroids
Direct Parent21-hydroxysteroids
Alternative Parents
Substituents
  • Progestogin-skeleton
  • 21-hydroxysteroid
  • Pregnane-skeleton
  • 20-oxosteroid
  • 3-oxo-delta-1,4-steroid
  • 3-oxosteroid
  • 17-hydroxysteroid
  • 11-hydroxysteroid
  • 11-beta-hydroxysteroid
  • 9-halo-steroid
  • Halo-steroid
  • Oxosteroid
  • Delta-1,4-steroid
  • Alpha-hydroxy ketone
  • Cyclic alcohol
  • Tertiary alcohol
  • Ketone
  • Fluorohydrin
  • Halohydrin
  • Secondary alcohol
  • Cyclic ketone
  • Organooxygen compound
  • Alcohol
  • Primary alcohol
  • Hydrocarbon derivative
  • Organic oxide
  • Carbonyl group
  • Organic oxygen compound
  • Alkyl halide
  • Alkyl fluoride
  • Organohalogen compound
  • Organofluoride
  • Aliphatic homopolycyclic compound
Molecular FrameworkAliphatic homopolycyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginEndogenous
Cellular Locations
  • Cytoplasm
  • Extracellular
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
ApplicationsNot Available
Biological RolesNot Available
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceNot Available
Experimental Properties
PropertyValue
Melting Point170-229 °C
Boiling PointNot Available
Solubility89 mg/L (at 25 °C)
LogP1.83
Predicted Properties
PropertyValueSource
Water Solubility0.05 g/LALOGPS
logP1.93ALOGPS
logP1.68ChemAxon
logS-3.9ALOGPS
pKa (Strongest Acidic)12.42ChemAxon
pKa (Strongest Basic)-3.3ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area94.83 ŲChemAxon
Rotatable Bond Count2ChemAxon
Refractivity102.49 m³·mol⁻¹ChemAxon
Polarizability40.83 ųChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyDeposition DateView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-02ai-2923000000-e31987dc12e5a702a42e2017-09-01View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (3 TMS) - 70eV, Positivesplash10-0006-2414490000-490d5cc0ad1eca76d44e2017-10-06View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot Available2021-10-12View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-qTof , Positivesplash10-0a4r-0696000000-1df7921eb1369fef69c42017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-qTof , Positivesplash10-00dj-3960000000-e9ee044790c0655981b12017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-01ot-0904000000-dbbc479b104fbe981ce72017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-0002-0903000000-c84b561c97b1277fed562017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-0002-0903000000-b498846e21073040b9052017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-0002-0900000000-b04e175289861dc518f12017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-0002-0900000000-b04e175289861dc518f12017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-01ot-0904000000-dbbc479b104fbe981ce72017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-0002-0903000000-c84b561c97b1277fed562017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-0002-0903000000-b498846e21073040b9052017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-006w-0719000000-d4feef3f83ca022aa94d2017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-0002-0913000000-3c8e5afb526637f1e8222017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-0002-0910000000-57f268bed9b190ee60662017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-0002-0900000000-cfdda545a27ec16c8b762017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-0002-0900000000-c70817ad99741f01b6752017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-00di-0009000000-ecbabc9fe90444b14afe2017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-05fr-0019000000-4161bdd8f3deed25b9bc2017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-002r-0594000000-bf4495b7906d53ad019d2017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-00ds-0980000000-c4e88ec70fa28252f6f72017-09-14View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-002f-0009000000-6926653590903a3ace6c2016-06-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-06vl-0019000000-301b3962f9291bee1ee92016-06-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0g4r-1294000000-8f3712f110452655373e2016-06-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0006-0009000000-a4ddb0d0eed36d96b76f2016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-05uu-1009000000-badd4f30582cf375bbdf2016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0a4i-8019000000-2bad3a1904cfc0e5431f2016-08-03View Spectrum
Toxicity Profile
Route of Exposure80-90%
Mechanism of ToxicityDexamethasone is a glucocorticoid agonist. Unbound dexamethasone crosses cell membranes and binds with high affinity to specific cytoplasmic glucocorticoid receptors. This complex binds to DNA elements (glucocorticoid response elements) which results in a modification of transcription and, hence, protein synthesis in order to achieve inhibition of leukocyte infiltration at the site of inflammation, interference in the function of mediators of inflammatory response, suppression of humoral immune responses, and reduction in edema or scar tissue. The antiinflammatory actions of dexamethasone are thought to involve phospholipase A2 inhibitory proteins, lipocortins, which control the biosynthesis of potent mediators of inflammation such as prostaglandins and leukotrienes.
MetabolismHepatic.
Toxicity ValuesOral, rat LD50: >3 gm/kg. Signs of overdose include retinal toxicity, glaucoma, subcapsular cataract, gastrointestinal bleeding, pancreatitis, aseptic bone necrosis, osteoporosis, myopathies, obesity, edemas, hypertension, proteinuria, diabetes, sleep disturbances, psychiatric syndromes, delayed wound healing, atrophy and fragility of the skin, ecchymosis, and pseudotumor cerebri.
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesInjection: for the treatment of endocrine disorders, rheumatic D=disorders, collagen diseases, dermatologic diseases, allergic statesc, ophthalmic diseases, gastrointestinal diseases, respiratory diseases, hematologic disorders, neoplastic diseases, edematous states, cerebral edema.
Ophthalmic ointment and solution: for the treatment of steroid responsive inflammatory conditions of the palpebral and bulbar conjunctiva, cornea, and anterior segment of the globe.
Ophthalmic solution only: for the treatment of steroid responsive inflammatory conditions of the external auditory meatus
Topic cream: for relief of the inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses
Oral aerosol: for the treatment of bronchial asthma and related corticosteroid responsive bronchospastic states intractable to adequate trial of conventional therapy
Intranasal aerosol: for the treatment of allergic ot inflammatory nasal conditions, and nasal polyps
Minimum Risk LevelNot Available
Health EffectsNot Available
SymptomsNot Available
TreatmentNot Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB01234
HMDB IDHMDB15364
PubChem Compound ID5743
ChEMBL IDCHEMBL384467
ChemSpider ID5541
KEGG IDC15643
UniProt IDNot Available
OMIM ID
ChEBI ID41879
BioCyc IDNot Available
CTD IDD003907
Stitch IDNot Available
PDB IDDEX
ACToR IDNot Available
Wikipedia LinkDexamethasone
References
Synthesis Reference

Fried, J.; US. Patent 2,852.51 1; September 16, 1958; assigned to Olin Mathieson Chemical Corporation.
Muller, G., Bardoneschi, R. and Jolly, J.; U.S. Patent 3,007,923; November 7, 1961; assigned to Les Laboratories Francais de Chimiotherapie, France.

MSDST3D4982.pdf
General References
  1. Bisgaard T: Analgesic treatment after laparoscopic cholecystectomy: a critical assessment of the evidence. Anesthesiology. 2006 Apr;104(4):835-46. [16571981 ]
  2. Chisti MJ, Bardhan PK, Huq S, Khan WA, Khan AM, Sharifuzzaman, Salam MA: High-dose intravenous dexamethasone in the management of diarrheal patients with enteric fever and encephalopathy. Southeast Asian J Trop Med Public Health. 2009 Sep;40(5):1065-73. [19842390 ]
  3. Ross DD, Alexander CS: Management of common symptoms in terminally ill patients: Part I. Fatigue, anorexia, cachexia, nausea and vomiting. Am Fam Physician. 2001 Sep 1;64(5):807-14. [11563572 ]
  4. Belanto JJ, Diaz-Perez SV, Magyar CE, Maxwell MM, Yilmaz Y, Topp K, Boso G, Jamieson CH, Cacalano NA, Jamieson CA: Dexamethasone induces dysferlin in myoblasts and enhances their myogenic differentiation. Neuromuscul Disord. 2010 Feb;20(2):111-21. doi: 10.1016/j.nmd.2009.12.003. Epub 2010 Jan 18. [20080405 ]
  5. Liu JZ, Huang YH, Hand PJ: Effects of dexamethasone on electroacupuncture analgesia and central nervous system metabolism. Acupunct Electrother Res. 1988;13(1):9-23. [2898201 ]
  6. Yannai, Shmuel. (2004) Dictionary of food compounds with CD-ROM: Additives, flavors, and ingredients. Boca Raton: Chapman & Hall/CRC.
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

Target Details
1. Glucocorticoid receptor
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 growth hormone (GH) stimulation and could reveal an essential role of hepatic GR in the control of body growth. Involved in chromatin remodeling. May play a negative role in adipogenesis through the regulation of lipolytic and antilipogenic genes expression.
Gene Name:
NR3C1
Uniprot ID:
P04150
Molecular Weight:
85658.57 Da
References
  1. Warne JP, John CD, Christian HC, Morris JF, Flower RJ, Sugden D, Solito E, Gillies GE, Buckingham JC: Gene deletion reveals roles for annexin A1 in the regulation of lipolysis and IL-6 release in epididymal adipose tissue. Am J Physiol Endocrinol Metab. 2006 Dec;291(6):E1264-73. Epub 2006 Jul 11. [16835395 ]
  2. 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. [16891588 ]
  3. Funato H, Kobayashi A, Watanabe Y: Differential effects of antidepressants on dexamethasone-induced nuclear translocation and expression of glucocorticoid receptor. Brain Res. 2006 Oct 30;1117(1):125-34. Epub 2006 Sep 7. [16956592 ]
  4. Vaitkuviene A, Ulinskaite A, Meskys R, Duburs G, Klusa V, Liutkevicius E: Study of the interaction of 1,4-dihydropyridine derivatives with glucocorticoid hormone receptors from the rat liver. Pharmacol Rep. 2006 Jul-Aug;58(4):551-8. [16963802 ]
  5. Wang D, Zhang H, Lang F, Yun CC: Acute activation of NHE3 by dexamethasone correlates with activation of SGK1 and requires a functional glucocorticoid receptor. Am J Physiol Cell Physiol. 2007 Jan;292(1):C396-404. Epub 2006 Sep 13. [16971495 ]
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
  7. Cheron A, Peltier J, Perez J, Bellocq A, Fouqueray B, Baud L: 15-deoxy-Delta12,14-prostaglandin J2 inhibits glucocorticoid binding and signaling in macrophages through a peroxisome proliferator-activated receptor gamma-independent process. J Immunol. 2004 Jun 15;172(12):7677-83. [15187150 ]
Target Details
2. Annexin A1
General Function:
Structural molecule activity
Specific Function:
Plays important roles in the innate immune response as effector of glucocorticoid-mediated responses and regulator of the inflammatory process. Has anti-inflammatory activity (PubMed:8425544). Plays a role in glucocorticoid-mediated down-regulation of the early phase of the inflammatory response (By similarity). Promotes resolution of inflammation and wound healing (PubMed:25664854). Functions at least in part by activating the formyl peptide receptors and downstream signaling cascades (PubMed:15187149, PubMed:25664854). Promotes chemotaxis of granulocytes and monocytes via activation of the formyl peptide receptors (PubMed:15187149). Contributes to the adaptive immune response by enhancing signaling cascades that are triggered by T-cell activation, regulates differentiation and proliferation of activated T-cells (PubMed:17008549). Promotes the differentiation of T-cells into Th1 cells and negatively regulates differentiation into Th2 cells (PubMed:17008549). Has no effect on unstimulated T cells (PubMed:17008549). Promotes rearrangement of the actin cytoskeleton, cell polarization and cell migration (PubMed:15187149). Negatively regulates hormone exocytosis via activation of the formyl peptide receptors and reorganization of the actin cytoskeleton (PubMed:19625660). Has high affinity for Ca(2+) and can bind up to eight Ca(2+) ions (By similarity). Displays Ca(2+)-dependent binding to phospholipid membranes (PubMed:2532504, PubMed:8557678). Plays a role in the formation of phagocytic cups and phagosomes. Plays a role in phagocytosis by mediating the Ca(2+)-dependent interaction between phagosomes and the actin cytoskeleton (By similarity).
Gene Name:
ANXA1
Uniprot ID:
P04083
Molecular Weight:
38713.855 Da
References
  1. Morand EF, Hall P, Hutchinson P, Yang YH: Regulation of annexin I in rheumatoid synovial cells by glucocorticoids and interleukin-1. Mediators Inflamm. 2006;2006(2):73835. [16883066 ]
  2. John CD, Theogaraj E, Christian HC, Morris JF, Smith SF, Buckingham JC: Time-specific effects of perinatal glucocorticoid treatment on anterior pituitary morphology, annexin 1 expression and adrenocorticotrophic hormone secretion in the adult female rat. J Neuroendocrinol. 2006 Dec;18(12):949-59. [17076770 ]
  3. Davies E, Omer S, Buckingham JC, Morris JF, Christian HC: Expression and externalization of annexin 1 in the adrenal gland: structure and function of the adrenal gland in annexin 1-null mutant mice. Endocrinology. 2007 Mar;148(3):1030-8. Epub 2006 Dec 7. [17158208 ]
  4. Wang C, Wang J, Guo HF, Liu RY: Involvement of annexin I in the dexamethasone-mediated upregulation of A549 cells phagocytosis of apoptotic eosinophils. Immunol Lett. 2007 Aug 15;111(2):103-10. Epub 2007 Jul 2. [17644190 ]
Target Details
3. Nitric oxide synthase, inducible
General Function:
Tetrahydrobiopterin binding
Specific Function:
Produces nitric oxide (NO) which is a messenger molecule with diverse functions throughout the body. In macrophages, NO mediates tumoricidal and bactericidal actions. Also has nitrosylase activity and mediates cysteine S-nitrosylation of cytoplasmic target proteins such COX2. As component of the iNOS-S100A8/9 transnitrosylase complex involved in the selective inflammatory stimulus-dependent S-nitrosylation of GAPDH on 'Cys-247' implicated in regulation of the GAIT complex activity and probably multiple targets including ANXA5, EZR, MSN and VIM.
Gene Name:
NOS2
Uniprot ID:
P35228
Molecular Weight:
131116.3 Da
References
  1. Soderberg M, Raffalli-Mathieu F, Lang MA: Regulation of the murine inducible nitric oxide synthase gene by dexamethasone involves a heterogeneous nuclear ribonucleoprotein I (hnRNPI) dependent pathway. Mol Immunol. 2007 May;44(12):3204-10. Epub 2007 Mar 26. [17379310 ]
  2. Huang H, Lavoie-Lamoureux A, Moran K, Lavoie JP: IL-4 stimulates the expression of CXCL-8, E-selectin, VEGF, and inducible nitric oxide synthase mRNA by equine pulmonary artery endothelial cells. Am J Physiol Lung Cell Mol Physiol. 2007 May;292(5):L1147-54. [17494951 ]
  3. Nandi J, Saud B, Zinkievich JM, Palma DT, Levine RA: 5-aminosalicylic acid improves indomethacin-induced enteropathy by inhibiting iNOS transcription in rats. Dig Dis Sci. 2008 Jan;53(1):123-32. Epub 2007 May 15. [17503181 ]
  4. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
Target Details
4. Nuclear receptor subfamily 0 group B member 1
General Function:
Transcription factor binding
Specific Function:
Orphan nuclear receptor. Component of a cascade required for the development of the hypothalamic-pituitary-adrenal-gonadal axis. Acts as a coregulatory protein that inhibits the transcriptional activity of other nuclear receptors through heterodimeric interactions. May also have a role in the development of the embryo and in the maintenance of embryonic stem cell pluripotency (By similarity).
Gene Name:
NR0B1
Uniprot ID:
P51843
Molecular Weight:
51717.185 Da
References
  1. Gummow BM, Scheys JO, Cancelli VR, Hammer GD: Reciprocal regulation of a glucocorticoid receptor-steroidogenic factor-1 transcription complex on the Dax-1 promoter by glucocorticoids and adrenocorticotropic hormone in the adrenal cortex. Mol Endocrinol. 2006 Nov;20(11):2711-23. Epub 2006 Jul 20. [16857744 ]
  2. Yu CC, Li PH: In vivo inhibition of steroidogenic acute regulatory protein expression by dexamethasone parallels induction of the negative transcription factor DAX-1. Endocrine. 2006 Dec;30(3):313-23. [17526944 ]
Target Details
5. Androgen receptor
General Function:
Zinc ion binding
Specific Function:
Steroid hormone receptors are ligand-activated transcription factors that regulate eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Transcription factor activity is modulated by bound coactivator and corepressor proteins. Transcription activation is down-regulated by NR0B2. Activated, but not phosphorylated, by HIPK3 and ZIPK/DAPK3.
Gene Name:
AR
Uniprot ID:
P10275
Molecular Weight:
98987.9 Da
References
  1. Krishnan AV, Zhao XY, Swami S, Brive L, Peehl DM, Ely KR, Feldman D: A glucocorticoid-responsive mutant androgen receptor exhibits unique ligand specificity: therapeutic implications for androgen-independent prostate cancer. Endocrinology. 2002 May;143(5):1889-900. [11956172 ]
Target Details
6. Aryl hydrocarbon receptor
General Function:
Transcription regulatory region dna binding
Specific Function:
Ligand-activated transcriptional activator. Binds to the XRE promoter region of genes it activates. Activates the expression of multiple phase I and II xenobiotic chemical metabolizing enzyme genes (such as the CYP1A1 gene). Mediates biochemical and toxic effects of halogenated aromatic hydrocarbons. Involved in cell-cycle regulation. Likely to play an important role in the development and maturation of many tissues. Regulates the circadian clock by inhibiting the basal and circadian expression of the core circadian component PER1. Inhibits PER1 by repressing the CLOCK-ARNTL/BMAL1 heterodimer mediated transcriptional activation of PER1.
Gene Name:
AHR
Uniprot ID:
P35869
Molecular Weight:
96146.705 Da
References
  1. Ricci MS, Toscano DG, Toscano WA Jr: ECC-1 human endometrial cells as a model system to study dioxin disruption of steroid hormone function. In Vitro Cell Dev Biol Anim. 1999 Apr;35(4):183-9. [10478797 ]
Target Details
7. Nuclear receptor subfamily 1 group I member 2
General Function:
Zinc ion binding
Specific Function:
Nuclear receptor that binds and is activated by variety of endogenous and xenobiotic compounds. Transcription factor that activates the transcription of multiple genes involved in the metabolism and secretion of potentially harmful xenobiotics, drugs and endogenous compounds. Activated by the antibiotic rifampicin and various plant metabolites, such as hyperforin, guggulipid, colupulone, and isoflavones. Response to specific ligands is species-specific. Activated by naturally occurring steroids, such as pregnenolone and progesterone. Binds to a response element in the promoters of the CYP3A4 and ABCB1/MDR1 genes.
Gene Name:
NR1I2
Uniprot ID:
O75469
Molecular Weight:
49761.245 Da
References
  1. Kretschmer XC, Baldwin WS: CAR and PXR: xenosensors of endocrine disrupters? Chem Biol Interact. 2005 Aug 15;155(3):111-28. [16054614 ]