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Identification
- Summary
Fluticasone is a corticosteroid indicated in the treatment of corticosteroid responsive dermatoses, asthma, and COPD.
- Generic Name
- Fluticasone
- DrugBank Accession Number
- DB13867
- Background
Fluticasone is a synthetic glucocorticoid available as 2 esters, Fluticasone furoate and Fluticasone propionate10,11,12,13Label. These drugs are available as inhalers, nasal, sprays, and topical treatments for various inflammatory indications10,11,12,13Label. Fluticasone propionate was first approved in 19908 and Fluticasone furoate was approved in 20079.
- Type
- Small Molecule
- Groups
- Approved, Experimental
- Structure
Structure for Fluticasone (DB13867)
- Weight
- Average: 444.51
Monoisotopic: 444.158215012 - Chemical Formula
- C22H27F3O4S
- Synonyms
- Fluticason
- Fluticasona
- Fluticasone
- Fluticasonum
Pharmacology
- Indication
Fluticasone's 2 esters are indicated as inhalers for the treatment and management of asthma by prophylaxisLabel13as well as inflammatory and pruritic dermatoses10. A Fluticasone propionate nasal spray is indicated for managing nonallergic rhinitis11 while the Fluticasone furoate nasal spray is indicated for treating season and perennial allergic rhinitis12,7.
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Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Used in combination for symptomatic treatment of Asthma Combination Product in combination with: Salmeterol (DB00938) •••••••••••• •••••• Used in combination to treat Asthma Combination Product in combination with: Formoterol (DB00983) •••••••••••• •••••••• •••••••••• Treatment of Asthma •••••••••••• Treatment of Bronchostenosis •••••••••••• Symptomatic treatment of Skin discomfort •••••••••••• •••••• •••••••• - Contraindications & Blackbox Warnings
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Systemically, in vitro experiments show Fluticasone furoate activates glucocorticoid receptors, inhibits nuclear factor kappa b, and inhibits lung eosinophilia in rats12,13,7. Fluticasone propionate performs similar activity but is not stated to affect nuclear factor kappa b11Label. Fluticasone propionate as a topical formulation is also associated with vasoconstriction in the skin10,3.
- Mechanism of action
Fluticasone furoate and Fluticasone propionate work through an unknown mechanism to affect the action of various cell types and mediators of inflammation12,13,11. In vitro experiments show Fluticasone furoate activating glucocorticoid receptors, inhibiting nuclear factor kappa b, and inhibiting lung eosinophilia in rats12,13,7. Fluticasone propionate performs similar activity but is not stated to affect nuclear factor kappa b11,10.
Target Actions Organism AGlucocorticoid receptor agonistHumans UProgesterone receptor agonistHumans UCytosolic phospholipase A2 inhibitorHumans UMineralocorticoid receptor antagonistHumans - Absorption
Intranasal exposure of Fluticasone furoate results in patients swallowing a larger portion of the dose12,3. However, absorption is poor and metabolism is high, therefore there is negligible systemic exposure with a nasal bioavailability of 0.50% and oral bioavialability of 1.26%12,1. Inhaled bioavailability is 13.9%13. A study of 24 healthy Caucasian males showed an inhaled bioavailability of 6.3-18.4%1.
Intranasal bioavailability of Fluticasone propionate is <2%, and oral bioavailability is <1%11Label. Intranasal exposure results in the majority of the dose being swallowed3. Topical absorption of Fluticasone propionate is very low but can change depending on a number of factors including integrity of the skin and the presence of inflammation or disease10. A study of 24 healthy Caucasian males showed an inhaled bioavailability of 9.0%1.
- Volume of distribution
608L at steady state for intravenous administration of Fluticasone furoate12. Other reports suggest the mean volume of distribution at steady state is 661L13. A study of 24 healthy Caucasian males showed a volume of distribution at steady state of 704L following intravenous administration1.
The volume of distribution of intravenous Fluticasone propionate is 4.2L/kg11Label. A study of 24 healthy Caucasian males showed a volume of distribution at steady state of 577L following intravenous administration1.
- Protein binding
Fluticasone furoate is >99%12 protein bound in serum and may be as high as 99.6%13.
Fluticasone propionate is 99% protein bound in serum11. Topical Fluticasone propionate is only 91% protein bound in serum however10.
- Metabolism
Fluticasone furoate and Fluticasone propionate are cleared from hepatic metabolism by cytochrome P450 3A412,13,11,4Label. Both are hydrolysed at the FIVE-S-fluoromethyl carbothioate group, forming an inactive metabolite12,10,3Label.
- Route of elimination
Fluticasone furoate is eliminated ≥90% in the feces and 1-2% in the urine12,13.
Fluticasone propionate is mainly eliminated in the feces with <5% eliminated in the urine11,5Label.
- Half-life
15.1 hours for intranasal Fluticasone furoate12 and 24 hours for the inhaled formulation13. A study of 24 healthy Caucasian males showed a half life of 13.6 hours following intravenous administration and 17.3-23.9 hours followed inhalation1.
7.8 hours for intravenous Fluticasone propionate11Label. A study of 24 healthy Caucasian males shows a half life of 14.0 hours following intravenous administration and 10.8 hours following inhalation1.
- Clearance
57.8L/h for Fluticasone furoate12. A study of 24 healthy Caucasian males showed a clearance of 71.8L/h following intravenous administration1.
1093mL/min for Fluticasone propionate11. A study of 24 healthy Caucasian males showed a clearance of 63.9L/h following intravenous administration1.
- Adverse Effects
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Fluticasone furoate administered nasally may be associated with adrenal suppression or an increase in QTc interval though the association has not been well demonstrated in studies12,2. Fluticasone furoate requires no dosage adjustment in renal impairment but must be used in caution in hepatic impairment due to the elimination mechanisms12,13. Fluticasone furoate is not associated with carcinogenicity, mutagenicity, or impairment of fertility12. There are no well controlled studies in pregnancy or lactation though animal studies have shown teratogenicity and hypoadrenalism in the offspring of treated mothers and other corticosteroids are known to be excreted in breast milk12. Generally, there are no reported adverse effects with fluticasone in pregnancy6. Pediatric patients should be given the lowest possible dose and monitored for reduction in growth velocity12,2. There is insufficient evidence to determine whether geriatric patients respond differently to other patients12. Systemic exposure may be 27-49% higher in Japanese, Korean, and Chinese patients compared to Caucasian patients13. Caution should be exercised in these patients and the benefit and risk should be assessed before deciding on a treatment12.
Fluticasone propionate's use in specific populations has not been well studied11. Fluticasone propionate is not carcinogenic, mutagenic, or clastogenic, nor did it affect fertility in animal studies11Label. Subcutaneous Fluticasone propionate has been shown to produce teratogenic effects in rats though oral administration does not10Label. Generally, there are no reported adverse effects with fluticasone in pregnancy6. Fluticasone propionate in human milk may cause growth suppression, effects on endogenous corticosteroid production, or other effects10,2. Pediatric patients treated with Fluticasone propionate ointment experienced adrenal suppression10. Geriatric patients treated with Fluticasone propionate did not show any difference in safety or efficacy compared to other patient groups, though older patients may be more sensitive to adverse effects10. There is no difference in the clearance of Fluticasone propionate across genders or raceLabel. Patients with hepatic impairment should be closely monitored due to the elimination mechanismLabel5.
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAbametapir The serum concentration of Fluticasone can be increased when it is combined with Abametapir. Abatacept The metabolism of Fluticasone can be increased when combined with Abatacept. Abemaciclib The metabolism of Abemaciclib can be increased when combined with Fluticasone. Acalabrutinib The metabolism of Acalabrutinib can be increased when combined with Fluticasone. Acarbose The risk or severity of hyperglycemia can be increased when Fluticasone is combined with Acarbose. - Food Interactions
- No interactions found.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Mixture Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image AFFERA Fluticasone (250 mcg) + Formoterol fumarate (10 mcg) Aerosol; Suspension Respiratory (inhalation) Mundipharma Pharmaceuticals S.R.L. 2014-07-08 2024-03-02 Italy 
AFFERA Fluticasone (125 mcg) + Formoterol fumarate (5 mcg) Aerosol; Suspension Respiratory (inhalation) Mundipharma Pharmaceuticals S.R.L. 2018-09-18 2023-06-16 Italy AFFERA Fluticasone (50 mcg) + Formoterol fumarate (5 mcg) Aerosol; Suspension Respiratory (inhalation) Mundipharma Pharmaceuticals S.R.L. 2018-09-18 2023-06-16 Italy AFFERA Fluticasone (125 mcg) + Formoterol fumarate (5 mcg) Aerosol; Suspension Respiratory (inhalation) Mundipharma Pharmaceuticals S.R.L. 2014-07-08 2024-03-02 Italy AFFERA Fluticasone (50 mcg) + Formoterol fumarate (5 mcg) Aerosol; Suspension Respiratory (inhalation) Mundipharma Pharmaceuticals S.R.L. 2014-07-08 2024-03-02 Italy
Categories
- ATC Codes
- R03BA05 — Fluticasone
- R03BA — Glucocorticoids
- R03B — OTHER DRUGS FOR OBSTRUCTIVE AIRWAY DISEASES, INHALANTS
- R03 — DRUGS FOR OBSTRUCTIVE AIRWAY DISEASES
- R — RESPIRATORY SYSTEM
- D07AC — Corticosteroids, potent (group III)
- D07A — CORTICOSTEROIDS, PLAIN
- D07 — CORTICOSTEROIDS, DERMATOLOGICAL PREPARATIONS
- D — DERMATOLOGICALS
- R03AK — Adrenergics in combination with corticosteroids or other drugs, excl. anticholinergics
- R03A — ADRENERGICS, INHALANTS
- R03 — DRUGS FOR OBSTRUCTIVE AIRWAY DISEASES
- R — RESPIRATORY SYSTEM
- R03AK — Adrenergics in combination with corticosteroids or other drugs, excl. anticholinergics
- R03A — ADRENERGICS, INHALANTS
- R03 — DRUGS FOR OBSTRUCTIVE AIRWAY DISEASES
- R — RESPIRATORY SYSTEM
- R01AD — Corticosteroids
- R01A — DECONGESTANTS AND OTHER NASAL PREPARATIONS FOR TOPICAL USE
- R01 — NASAL PREPARATIONS
- R — RESPIRATORY SYSTEM
- Drug Categories
- Adrenal Cortex Hormones
- Androstadienes
- Androstanes
- Androstenes
- Anti-Allergic Agents
- Anti-Asthmatic Agents
- Anti-Inflammatory Agents
- Autonomic Agents
- Bronchodilator Agents
- Corticosteroid Hormone Receptor Agonists
- Corticosteroids
- Corticosteroids, Dermatological Preparations
- Corticosteroids, Potent (Group III)
- Cytochrome P-450 CYP2C8 Inhibitors
- Cytochrome P-450 CYP2C8 Inhibitors (strong)
- Cytochrome P-450 CYP3A Inducers
- Cytochrome P-450 CYP3A Inhibitors
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Inducers
- Cytochrome P-450 CYP3A4 Inducers (strength unknown)
- Cytochrome P-450 CYP3A4 Inhibitors
- Cytochrome P-450 CYP3A4 Inhibitors (strength unknown)
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 CYP3A5 Inducers
- Cytochrome P-450 CYP3A5 Inducers (strength unknown)
- Cytochrome P-450 CYP3A5 Inhibitors
- Cytochrome P-450 CYP3A5 Inhibitors (strength unknown)
- Cytochrome P-450 CYP3A5 Substrates
- Cytochrome P-450 CYP3A7 Substrates
- Cytochrome P-450 Enzyme Inducers
- Cytochrome P-450 Enzyme Inhibitors
- Cytochrome P-450 Substrates
- Dermatologicals
- Drugs for Obstructive Airway Diseases
- Fused-Ring Compounds
- Glucocorticoids
- Hyperglycemia-Associated Agents
- Immunosuppressive Agents
- Nasal Preparations
- OATP1B1/SLCO1B1 Inhibitors
- P-glycoprotein substrates
- Peripheral Nervous System Agents
- Respiratory System Agents
- Steroids
- Thyroxine-binding globulin inhibitors
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as androgens and derivatives. These are 3-hydroxylated C19 steroid hormones. They are known to favor the development of masculine characteristics. They also show profound effects on scalp and body hair in humans.
- Kingdom
- Organic compounds
- Super Class
- Lipids and lipid-like molecules
- Class
- Steroids and steroid derivatives
- Sub Class
- Androstane steroids
- Direct Parent
- Androgens and derivatives
- Alternative Parents
- 11-beta-hydroxysteroids / 17-hydroxysteroids / 3-oxo delta-1,4-steroids / Halogenated steroids / Delta-1,4-steroids / Tertiary alcohols / Thioesters / Secondary alcohols / Carbothioic S-esters / Cyclic alcohols and derivatives show 8 more
- Substituents
- 11-beta-hydroxysteroid / 11-hydroxysteroid / 17-hydroxysteroid / 3-oxo-delta-1,4-steroid / 3-oxosteroid / 6-halo-steroid / 9-halo-steroid / Alcohol / Aliphatic homopolycyclic compound / Alkyl fluoride show 26 more
- Molecular Framework
- Aliphatic homopolycyclic compounds
- External Descriptors
- thioester, 11beta-hydroxy steroid, 17alpha-hydroxy steroid, 3-oxo Delta(4)-steroid, fluorinated steroid, corticosteroid (CHEBI:5134)
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- CUT2W21N7U
- CAS number
- 90566-53-3
- InChI Key
- MGNNYOODZCAHBA-GQKYHHCASA-N
- InChI
- InChI=1S/C22H27F3O4S/c1-11-6-13-14-8-16(24)15-7-12(26)4-5-19(15,2)21(14,25)17(27)9-20(13,3)22(11,29)18(28)30-10-23/h4-5,7,11,13-14,16-17,27,29H,6,8-10H2,1-3H3/t11-,13+,14+,16+,17+,19+,20+,21+,22+/m1/s1
- IUPAC Name
- (1R,2R,3aS,3bS,5S,9aS,9bR,10S,11aS)-5,9b-difluoro-1-{[(fluoromethyl)sulfanyl]carbonyl}-1,10-dihydroxy-2,9a,11a-trimethyl-1H,2H,3H,3aH,3bH,4H,5H,7H,9aH,9bH,10H,11H,11aH-cyclopenta[a]phenanthren-7-one
- SMILES
- [H][C@@]12C[C@@H](C)[C@](O)(C(=O)SCF)[C@@]1(C)C[C@H](O)[C@@]1(F)[C@@]2([H])C[C@H](F)C2=CC(=O)C=C[C@]12C
References
- General References
- Allen A, Bareille PJ, Rousell VM: Fluticasone furoate, a novel inhaled corticosteroid, demonstrates prolonged lung absorption kinetics in man compared with inhaled fluticasone propionate. Clin Pharmacokinet. 2013 Jan;52(1):37-42. doi: 10.1007/s40262-012-0021-x. [Article]
- Allen A, Schenkenberger I, Trivedi R, Cole J, Hicks W, Gul N, Jacques L: Inhaled fluticasone furoate/vilanterol does not affect hypothalamic-pituitary-adrenal axis function in adolescent and adult asthma: randomised, double-blind, placebo-controlled study. Clin Respir J. 2013 Oct;7(4):397-406. doi: 10.1111/crj.12026. Epub 2013 Jun 5. [Article]
- Phillipps GH: Structure-activity relationships of topically active steroids: the selection of fluticasone propionate. Respir Med. 1990 Nov;84 Suppl A:19-23. [Article]
- Harding SM: The human pharmacology of fluticasone propionate. Respir Med. 1990 Nov;84 Suppl A:25-9. [Article]
- Crim C, Pierre LN, Daley-Yates PT: A review of the pharmacology and pharmacokinetics of inhaled fluticasone propionate and mometasone furoate. Clin Ther. 2001 Sep;23(9):1339-54. [Article]
- Choi JS, Han JY, Kim MY, Velazquez-Armenta EY, Nava-Ocampo AA: Pregnancy outcomes in women using inhaled fluticasone during pregnancy: a case series. Allergol Immunopathol (Madr). 2007 Nov-Dec;35(6):239-42. [Article]
- Spadijer Mirkovic C, Peric A, Vukomanovic Durdevic B, Vojvodic D: Effects of Fluticasone Furoate Nasal Spray on Parameters of Eosinophilic Inflammation in Patients With Nasal Polyposis and Perennial Allergic Rhinitis. Ann Otol Rhinol Laryngol. 2017 Aug;126(8):573-580. doi: 10.1177/0003489417713505. Epub 2017 Jun 6. [Article]
- FDA Approved Drug Products December 1990 [Link]
- FDA Fluticasone Furoate Approval 2007 [Link]
- Fluticasone Propionate (Cutivate) Ointment FDA Label [File]
- Fluticasone Propionate (Flonase) Nasal Spray FDA Label [File]
- Fluticasone Furoate (Veramyst) Nasal Spray FDA Label [File]
- Fluticasone Furoate (Arnuity Ellipta) FDA Label [File]
- External Links
- KEGG Drug
- D07981
- KEGG Compound
- C07815
- ChemSpider
- 4470631
- 41126
- ChEBI
- 5134
- ChEMBL
- CHEMBL1201396
- ZINC
- ZINC000004097438
- Wikipedia
- Fluticasone
- FDA label
- Download (651 KB)
Clinical Trials
- Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package Phase Status Purpose Conditions Count Start Date Why Stopped 100+ additional columns Unlock 175K+ rows when you subscribe.View sample dataNot Available Active Not Recruiting Not Available Asthma 1 somestatus stop reason just information to hide Not Available Completed Not Available Allergic Rhinitis (AR) 1 somestatus stop reason just information to hide Not Available Completed Not Available Asthma 1 somestatus stop reason just information to hide Not Available Completed Not Available Chronic Obstructive Pulmonary Disease (COPD) 4 somestatus stop reason just information to hide Not Available Completed Not Available Respiratory Disorders 2 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Aerosol; suspension Respiratory (inhalation) Ointment Cutaneous Ointment Cutaneous 0005 % Cream Cutaneous 0.05 % Cream Cutaneous 0.5 MG/G Ointment 0.05 MG/G Ointment 0005 % Spray Nasal 50 MICROGRAMMI Powder Respiratory (inhalation) 250 μg Powder Respiratory (inhalation) 500 μg Powder Respiratory (inhalation) Cream Cutaneous Aerosol Respiratory (inhalation) 125 μg Aerosol Respiratory (inhalation) 25 μg Aerosol Respiratory (inhalation) 250 μg Aerosol Respiratory (inhalation) 50 μg Aerosol, metered Respiratory (inhalation) 125 MCG Aerosol, metered Respiratory (inhalation) 25 MCG Aerosol, metered Respiratory (inhalation) 250 MCG Aerosol, metered Respiratory (inhalation) 50 MCG Powder, metered Respiratory (inhalation) 100 MCG Powder, metered Respiratory (inhalation) 250 MCG Powder, metered Respiratory (inhalation) 50 MCG Powder, metered Respiratory (inhalation) 500 MCG Spray, suspension Respiratory (inhalation) 2 MG/2ML Spray, suspension Respiratory (inhalation) 500 MCG/2ML Aerosol, metered Respiratory (inhalation) 125 MICROGRAMMI Aerosol, metered Respiratory (inhalation) 250 MICROGRAMMI Aerosol Respiratory (inhalation) Powder, metered Respiratory (inhalation) Solution / drops Nasal 400 MICROGRAMMI Spray Nasal 50 MCG Aerosol, metered Respiratory (inhalation) Spray Nasal Aerosol Buccal Aerosol, metered Respiratory (inhalation) 125 mcg/1dose Spray, metered Respiratory (inhalation) 0.5 mg/2ml Spray, metered Respiratory (inhalation) 2 mg/2ml - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
- Not Available
- Predicted Properties
Property Value Source Water Solubility 0.0344 mg/mL ALOGPS logP 2.69 ALOGPS logP 2.58 Chemaxon logS -4.1 ALOGPS pKa (Strongest Acidic) 12.19 Chemaxon pKa (Strongest Basic) -3.4 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 4 Chemaxon Hydrogen Donor Count 2 Chemaxon Polar Surface Area 74.6 Å2 Chemaxon Rotatable Bond Count 3 Chemaxon Refractivity 107.87 m3·mol-1 Chemaxon Polarizability 43.32 Å3 Chemaxon Number of Rings 4 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-056r-0002900000-84f17087da032f80246e Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-002f-9007500000-e026e8e49992034d760f Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-003b-0117900000-b08cb799159e73bc9b87 Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-0006-9001000000-0622dbc428f8aba15a44 Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-056r-0109000000-204971b3216c31a8de61 Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-05mo-1492100000-d10e15e909ffdd746e62 Predicted 1H NMR Spectrum 1D NMR Not Applicable Predicted 13C NMR Spectrum 1D NMR Not Applicable - Chromatographic Properties
Collision Cross Sections (CCS)
Not Available
Targets
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- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Agonist
- General Function
- Receptor for glucocorticoids (GC) (PubMed:27120390, PubMed:37478846). 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 (PubMed:28139699). Affects inflammatory responses, cellular proliferation and differentiation in target tissues. Involved in chromatin remodeling (PubMed:9590696). Plays a role in rapid mRNA degradation by binding to the 5' UTR of target mRNAs and interacting with PNRC2 in a ligand-dependent manner which recruits the RNA helicase UPF1 and the mRNA-decapping enzyme DCP1A, leading to RNA decay (PubMed:25775514). 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 (By similarity)
- Specific Function
- core promoter sequence-specific DNA binding
- Gene Name
- NR3C1
- Uniprot ID
- P04150
- Uniprot Name
- Glucocorticoid receptor
- Molecular Weight
- 85658.57 Da
References
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Agonist
- General Function
- The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Depending on the isoform, progesterone receptor functions as a transcriptional activator or repressor
- Specific Function
- ATPase binding
- Gene Name
- PGR
- Uniprot ID
- P06401
- Uniprot Name
- Progesterone receptor
- Molecular Weight
- 98979.96 Da
References
- Issar M, Sahasranaman S, Buchwald P, Hochhaus G: Differences in the glucocorticoid to progesterone receptor selectivity of inhaled glucocorticoids. Eur Respir J. 2006 Mar;27(3):511-6. [Article]
- Austin RJ, Maschera B, Walker A, Fairbairn L, Meldrum E, Farrow SN, Uings IJ: Mometasone furoate is a less specific glucocorticoid than fluticasone propionate. Eur Respir J. 2002 Dec;20(6):1386-92. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Has primarily calcium-dependent phospholipase and lysophospholipase activities, with a major role in membrane lipid remodeling and biosynthesis of lipid mediators of the inflammatory response (PubMed:10358058, PubMed:14709560, PubMed:16617059, PubMed:17472963, PubMed:18451993, PubMed:27642067, PubMed:7794891, PubMed:8619991, PubMed:8702602, PubMed:9425121). Plays an important role in embryo implantation and parturition through its ability to trigger prostanoid production (By similarity). Preferentially hydrolyzes the ester bond of the fatty acyl group attached at sn-2 position of phospholipids (phospholipase A2 activity) (PubMed:10358058, PubMed:17472963, PubMed:18451993, PubMed:7794891, PubMed:8619991, PubMed:9425121). Selectively hydrolyzes sn-2 arachidonoyl group from membrane phospholipids, providing the precursor for eicosanoid biosynthesis via the cyclooxygenase pathway (PubMed:10358058, PubMed:17472963, PubMed:18451993, PubMed:7794891, PubMed:9425121). In an alternative pathway of eicosanoid biosynthesis, hydrolyzes sn-2 fatty acyl chain of eicosanoid lysophopholipids to release free bioactive eicosanoids (PubMed:27642067). Hydrolyzes the ester bond of the fatty acyl group attached at sn-1 position of phospholipids (phospholipase A1 activity) only if an ether linkage rather than an ester linkage is present at the sn-2 position. This hydrolysis is not stereospecific (PubMed:7794891). Has calcium-independent phospholipase A2 and lysophospholipase activities in the presence of phosphoinositides (PubMed:12672805). Has O-acyltransferase activity. Catalyzes the transfer of fatty acyl chains from phospholipids to a primary hydroxyl group of glycerol (sn-1 or sn-3), potentially contributing to monoacylglycerol synthesis (PubMed:7794891)
- Specific Function
- calcium ion binding
- Gene Name
- PLA2G4A
- Uniprot ID
- P47712
- Uniprot Name
- Cytosolic phospholipase A2
- Molecular Weight
- 85238.2 Da
References
- Sano A, Munoz NM, Sano H, Choi J, Zhu X, Jacobs B, Leff AR: Inhibition of cPLA2 translocation and leukotriene C4 secretion by fluticasone propionate in exogenously activated human eosinophils. Am J Respir Crit Care Med. 1999 Jun;159(6):1903-9. [Article]
- Myo S, Zhu X, Myou S, Meliton AY, Liu J, Boetticher E, Lambertino AT, Xu C, Munoz NM, Leff AR: Additive blockade of beta 2-integrin adhesion of eosinophils by salmeterol and fluticasone propionate. Eur Respir J. 2004 Apr;23(4):511-7. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Antagonist
- General Function
- Receptor for both mineralocorticoids (MC) such as aldosterone and glucocorticoids (GC) such as corticosterone or cortisol. Binds to mineralocorticoid response elements (MRE) and transactivates target genes. The effect of MC is to increase ion and water transport and thus raise extracellular fluid volume and blood pressure and lower potassium levels
- Specific Function
- DNA-binding transcription factor activity
- Gene Name
- NR3C2
- Uniprot ID
- P08235
- Uniprot Name
- Mineralocorticoid receptor
- Molecular Weight
- 107080.615 Da
References
- Austin RJ, Maschera B, Walker A, Fairbairn L, Meldrum E, Farrow SN, Uings IJ: Mometasone furoate is a less specific glucocorticoid than fluticasone propionate. Eur Respir J. 2002 Dec;20(6):1386-92. [Article]
- Issar M, Sahasranaman S, Buchwald P, Hochhaus G: Differences in the glucocorticoid to progesterone receptor selectivity of inhaled glucocorticoids. Eur Respir J. 2006 Mar;27(3):511-6. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- SubstrateInhibitorInducer
- Curator comments
- Induction likely occurs through transcriptional modulation by the glucocorticoid receptor.
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of sterols, steroid hormones, retinoids and fatty acids (PubMed:10681376, PubMed:11093772, PubMed:11555828, PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:19965576, PubMed:20702771, PubMed:21490593, PubMed:21576599). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase). Catalyzes the hydroxylation of carbon-hydrogen bonds (PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:21490593, PubMed:21576599, PubMed:2732228). Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1) and 17beta-estradiol (E2), namely 2-hydroxy E1 and E2, as well as D-ring hydroxylated E1 and E2 at the C-16 position (PubMed:11555828, PubMed:12865317, PubMed:14559847). Plays a role in the metabolism of androgens, particularly in oxidative deactivation of testosterone (PubMed:15373842, PubMed:15764715, PubMed:22773874, PubMed:2732228). Metabolizes testosterone to less biologically active 2beta- and 6beta-hydroxytestosterones (PubMed:15373842, PubMed:15764715, PubMed:2732228). Contributes to the formation of hydroxycholesterols (oxysterols), particularly A-ring hydroxylated cholesterol at the C-4beta position, and side chain hydroxylated cholesterol at the C-25 position, likely contributing to cholesterol degradation and bile acid biosynthesis (PubMed:21576599). Catalyzes bisallylic hydroxylation of polyunsaturated fatty acids (PUFA) (PubMed:9435160). Catalyzes the epoxidation of double bonds of PUFA with a preference for the last double bond (PubMed:19965576). Metabolizes endocannabinoid arachidonoylethanolamide (anandamide) to 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed:20702771). Plays a role in the metabolism of retinoids. Displays high catalytic activity for oxidation of all-trans-retinol to all-trans-retinal, a rate-limiting step for the biosynthesis of all-trans-retinoic acid (atRA) (PubMed:10681376). Further metabolizes atRA toward 4-hydroxyretinoate and may play a role in hepatic atRA clearance (PubMed:11093772). Responsible for oxidative metabolism of xenobiotics. Acts as a 2-exo-monooxygenase for plant lipid 1,8-cineole (eucalyptol) (PubMed:11159812). Metabolizes the majority of the administered drugs. Catalyzes sulfoxidation of the anthelmintics albendazole and fenbendazole (PubMed:10759686). Hydroxylates antimalarial drug quinine (PubMed:8968357). Acts as a 1,4-cineole 2-exo-monooxygenase (PubMed:11695850). Also involved in vitamin D catabolism and calcium homeostasis. Catalyzes the inactivation of the active hormone calcitriol (1-alpha,25-dihydroxyvitamin D(3)) (PubMed:29461981)
- Specific Function
- 1,8-cineole 2-exo-monooxygenase activity
- Gene Name
- CYP3A4
- Uniprot ID
- P08684
- Uniprot Name
- Cytochrome P450 3A4
- Molecular Weight
- 57342.67 Da
References
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- SubstrateInhibitorInducer
- Curator comments
- Induction likely occurs through transcriptional modulation by the glucocorticoid receptor.
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of steroid hormones and vitamins (PubMed:10681376, PubMed:11093772, PubMed:12865317, PubMed:2732228). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase). Catalyzes the hydroxylation of carbon-hydrogen bonds (PubMed:10681376, PubMed:11093772, PubMed:12865317, PubMed:2732228). Exhibits high catalytic activity for the formation of catechol estrogens from 17beta-estradiol (E2) and estrone (E1), namely 2-hydroxy E1 and E2 (PubMed:12865317). Catalyzes 6beta-hydroxylation of the steroid hormones testosterone, progesterone, and androstenedione (PubMed:2732228). Catalyzes the oxidative conversion of all-trans-retinol to all-trans-retinal, a rate-limiting step for the biosynthesis of all-trans-retinoic acid (atRA) (PubMed:10681376). Further metabolizes all trans-retinoic acid (atRA) to 4-hydroxyretinoate and may play a role in hepatic atRA clearance (PubMed:11093772). Also involved in the oxidative metabolism of xenobiotics, including calcium channel blocking drug nifedipine and immunosuppressive drug cyclosporine (PubMed:2732228)
- Specific Function
- aromatase activity
- Gene Name
- CYP3A5
- Uniprot ID
- P20815
- Uniprot Name
- Cytochrome P450 3A5
- Molecular Weight
- 57108.065 Da
References
- Pearce RE, Leeder JS, Kearns GL: Biotransformation of fluticasone: in vitro characterization. Drug Metab Dispos. 2006 Jun;34(6):1035-40. Epub 2006 Mar 24. [Article]
- Murai T, Reilly CA, Ward RM, Yost GS: The inhaled glucocorticoid fluticasone propionate efficiently inactivates cytochrome P450 3A5, a predominant lung P450 enzyme. Chem Res Toxicol. 2010 Aug 16;23(8):1356-64. doi: 10.1021/tx100124k. [Article]
- Dvorak Z, Pavek P: Regulation of drug-metabolizing cytochrome P450 enzymes by glucocorticoids. Drug Metab Rev. 2010 Nov;42(4):621-35. doi: 10.3109/03602532.2010.484462. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of steroid hormones and vitamins during embryogenesis (PubMed:11093772, PubMed:12865317, PubMed:14559847, PubMed:17178770, PubMed:9555064). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:11093772, PubMed:12865317, PubMed:14559847, PubMed:17178770, PubMed:9555064). Catalyzes the hydroxylation of carbon-hydrogen bonds. Metabolizes 3beta-hydroxyandrost-5-en-17-one (dehydroepiandrosterone, DHEA), a precursor in the biosynthesis of androgen and estrogen steroid hormones (PubMed:17178770, PubMed:9555064). Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1), particularly D-ring hydroxylated estrone at the C16-alpha position (PubMed:12865317, PubMed:14559847). Mainly hydroxylates all trans-retinoic acid (atRA) to 4-hydroxyretinoate and may play a role in atRA clearance during fetal development (PubMed:11093772). Also involved in the oxidative metabolism of xenobiotics including anticonvulsants (PubMed:9555064)
- Specific Function
- all-trans retinoic acid 18-hydroxylase activity
- Gene Name
- CYP3A7
- Uniprot ID
- P24462
- Uniprot Name
- Cytochrome P450 3A7
- Molecular Weight
- 57469.95 Da
References
- Pearce RE, Leeder JS, Kearns GL: Biotransformation of fluticasone: in vitro characterization. Drug Metab Dispos. 2006 Jun;34(6):1035-40. Epub 2006 Mar 24. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Inhibitor
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids, steroid hormones and vitamins (PubMed:11093772, PubMed:14559847, PubMed:15766564, PubMed:19965576, PubMed:7574697). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:11093772, PubMed:14559847, PubMed:15766564, PubMed:19965576, PubMed:7574697). Primarily catalyzes the epoxidation of double bonds of polyunsaturated fatty acids (PUFA) with a preference for the last double bond (PubMed:15766564, PubMed:19965576, PubMed:7574697). Catalyzes the hydroxylation of carbon-hydrogen bonds. Metabolizes all trans-retinoic acid toward its 4-hydroxylated form (PubMed:11093772). Displays 16-alpha hydroxylase activity toward estrogen steroid hormones, 17beta-estradiol (E2) and estrone (E1) (PubMed:14559847). Plays a role in the oxidative metabolism of xenobiotics. It is the principal enzyme responsible for the metabolism of the anti-cancer drug paclitaxel (taxol) (PubMed:26427316)
- Specific Function
- arachidonic acid epoxygenase activity
- Gene Name
- CYP2C8
- Uniprot ID
- P10632
- Uniprot Name
- Cytochrome P450 2C8
- Molecular Weight
- 55824.275 Da
References
Carriers
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Major transport protein for glucocorticoids and progestins in the blood of almost all vertebrate species
- Specific Function
- serine-type endopeptidase inhibitor activity
- Gene Name
- SERPINA6
- Uniprot ID
- P08185
- Uniprot Name
- Corticosteroid-binding globulin
- Molecular Weight
- 45140.49 Da
References
- Gardill BR, Vogl MR, Lin HY, Hammond GL, Muller YA: Corticosteroid-binding globulin: structure-function implications from species differences. PLoS One. 2012;7(12):e52759. doi: 10.1371/journal.pone.0052759. Epub 2012 Dec 26. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General Function
- Translocates drugs and phospholipids across the membrane (PubMed:2897240, PubMed:35970996, PubMed:8898203, PubMed:9038218). Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of phosphatidylcholine, phosphatidylethanolamine, beta-D-glucosylceramides and sphingomyelins (PubMed:8898203). Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells (PubMed:2897240, PubMed:35970996, PubMed:9038218)
- Specific Function
- ABC-type xenobiotic transporter activity
- Gene Name
- ABCB1
- Uniprot ID
- P08183
- Uniprot Name
- ATP-dependent translocase ABCB1
- Molecular Weight
- 141477.255 Da
References
- FDA reports [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Inhibitor
- General Function
- Mediates the Na(+)-independent uptake of organic anions (PubMed:10358072, PubMed:15159445, PubMed:17412826). Shows broad substrate specificity, can transport both organic anions such as bile acid taurocholate (cholyltaurine) and conjugated steroids (dehydroepiandrosterone 3-sulfate, 17-beta-glucuronosyl estradiol, and estrone 3-sulfate), as well as eicosanoids (prostaglandin E2, thromboxane B2, leukotriene C4, and leukotriene E4), and thyroid hormones (T4/L-thyroxine, and T3/3,3',5'-triiodo-L-thyronine) (PubMed:10358072, PubMed:10601278, PubMed:10873595, PubMed:11159893, PubMed:12196548, PubMed:12568656, PubMed:15159445, PubMed:15970799, PubMed:16627748, PubMed:17412826, PubMed:19129463, PubMed:26979622). Can take up bilirubin glucuronides from plasma into the liver, contributing to the detoxification-enhancing liver-blood shuttling loop (PubMed:22232210). Involved in the clearance of endogenous and exogenous substrates from the liver (PubMed:10358072, PubMed:10601278). Transports coproporphyrin I and III, by-products of heme synthesis, and may be involved in their hepatic disposition (PubMed:26383540). May contribute to regulate the transport of organic compounds in testes across the blood-testis-barrier (Probable). Can transport HMG-CoA reductase inhibitors (also known as statins), such as pravastatin and pitavastatin, a clinically important class of hypolipidemic drugs (PubMed:10601278, PubMed:15159445, PubMed:15970799). May play an important role in plasma and tissue distribution of the structurally diverse chemotherapeutic drug methotrexate (PubMed:23243220). May also transport antihypertension agents, such as the angiotensin-converting enzyme (ACE) inhibitor prodrug enalapril, and the highly selective angiotensin II AT1-receptor antagonist valsartan, in the liver (PubMed:16624871, PubMed:16627748). Shows a pH-sensitive substrate specificity towards prostaglandin E2 and T4 which may be ascribed to the protonation state of the binding site and leads to a stimulation of substrate transport in an acidic microenvironment (PubMed:19129463). Hydrogencarbonate/HCO3(-) acts as the probable counteranion that exchanges for organic anions (PubMed:19129463)
- Specific Function
- bile acid transmembrane transporter activity
- Gene Name
- SLCO1B1
- Uniprot ID
- Q9Y6L6
- Uniprot Name
- Solute carrier organic anion transporter family member 1B1
- Molecular Weight
- 76447.99 Da
References
- FDA reports [Link]
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Translocates drugs and phospholipids across the membrane (PubMed:2897240, PubMed:35970996, PubMed:8898203, PubMed:9038218). Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of phosphatidylcholine, phosphatidylethanolamine, beta-D-glucosylceramides and sphingomyelins (PubMed:8898203). Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells (PubMed:2897240, PubMed:35970996, PubMed:9038218)
- Specific Function
- ABC-type xenobiotic transporter activity
- Gene Name
- ABCB1
- Uniprot ID
- P08183
- Uniprot Name
- ATP-dependent translocase ABCB1
- Molecular Weight
- 141477.255 Da
References
- Hughes SC, Shardlow PC, Hollis FJ, Scott RJ, Motivaras DS, Allen A, Rousell VM: Metabolism and disposition of fluticasone furoate, an enhanced-affinity glucocorticoid, in humans. Drug Metab Dispos. 2008 Nov;36(11):2337-44. doi: 10.1124/dmd.108.022137. Epub 2008 Aug 11. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Mediates the Na(+)-independent uptake of organic anions (PubMed:10358072, PubMed:15159445, PubMed:17412826). Shows broad substrate specificity, can transport both organic anions such as bile acid taurocholate (cholyltaurine) and conjugated steroids (dehydroepiandrosterone 3-sulfate, 17-beta-glucuronosyl estradiol, and estrone 3-sulfate), as well as eicosanoids (prostaglandin E2, thromboxane B2, leukotriene C4, and leukotriene E4), and thyroid hormones (T4/L-thyroxine, and T3/3,3',5'-triiodo-L-thyronine) (PubMed:10358072, PubMed:10601278, PubMed:10873595, PubMed:11159893, PubMed:12196548, PubMed:12568656, PubMed:15159445, PubMed:15970799, PubMed:16627748, PubMed:17412826, PubMed:19129463, PubMed:26979622). Can take up bilirubin glucuronides from plasma into the liver, contributing to the detoxification-enhancing liver-blood shuttling loop (PubMed:22232210). Involved in the clearance of endogenous and exogenous substrates from the liver (PubMed:10358072, PubMed:10601278). Transports coproporphyrin I and III, by-products of heme synthesis, and may be involved in their hepatic disposition (PubMed:26383540). May contribute to regulate the transport of organic compounds in testes across the blood-testis-barrier (Probable). Can transport HMG-CoA reductase inhibitors (also known as statins), such as pravastatin and pitavastatin, a clinically important class of hypolipidemic drugs (PubMed:10601278, PubMed:15159445, PubMed:15970799). May play an important role in plasma and tissue distribution of the structurally diverse chemotherapeutic drug methotrexate (PubMed:23243220). May also transport antihypertension agents, such as the angiotensin-converting enzyme (ACE) inhibitor prodrug enalapril, and the highly selective angiotensin II AT1-receptor antagonist valsartan, in the liver (PubMed:16624871, PubMed:16627748). Shows a pH-sensitive substrate specificity towards prostaglandin E2 and T4 which may be ascribed to the protonation state of the binding site and leads to a stimulation of substrate transport in an acidic microenvironment (PubMed:19129463). Hydrogencarbonate/HCO3(-) acts as the probable counteranion that exchanges for organic anions (PubMed:19129463)
- Specific Function
- bile acid transmembrane transporter activity
- Gene Name
- SLCO1B1
- Uniprot ID
- Q9Y6L6
- Uniprot Name
- Solute carrier organic anion transporter family member 1B1
- Molecular Weight
- 76447.99 Da
References
- FDA reports [Link]
Drug created at July 05, 2017 00:00 / Updated at July 03, 2021 01:49