Explore a selection of our essential drug information below, or:
Identification
- Summary
Roflumilast is a selective phosphodiesterase-4 inhibitor indicated to decrease the risk of exacerbations in patients with severe chronic obstructive pulmonary disease (COPD) and to treat skin conditions such as plaque psoriasis and atopic dermatitis.
- Brand Names
- Daliresp, Zoryve
- Generic Name
- Roflumilast
- DrugBank Accession Number
- DB01656
- Background
Roflumilast is a highly selective phosphodiesterase-4 (PDE4) inhibitor.7 PDE4 is a major cyclic-3',5′-adenosinemonophosphate (cyclic AMP, cAMP)-metabolizing enzyme 9 expressed on nearly all immune and pro-inflammatory cells, in addition to structural cells like those of the smooth muscle or epithelium.7 The resultant increase in intracellular cAMP induced by roflumilast's inhibition of PDE4 is thought to mediate its disease-modifying effects, although its precise mechanism of action has yet to be elucidated.9,7
The oral formulation of roflumilast is indicated to manage chronic obstructive pulmonary disease.13 It was first approved by the EMA in July 2010, and by the FDA in January 2018.9 Roflumilast topical cream is indicated to treat plaque psoriasis. The cream formulation was first approved by the FDA in July 2022 10 and by Health Canada in April 2023.12 On December 15, 2023, the FDA approved a new topical foam formulation of roflumilast for the treatment of seborrheic dermatitis in patients aged 9 years and older.15
- Type
- Small Molecule
- Groups
- Approved
- Structure
Structure for Roflumilast (DB01656)
- Weight
- Average: 403.207
Monoisotopic: 402.034954148 - Chemical Formula
- C17H14Cl2F2N2O3
- Synonyms
- Roflumilast
- Roflumilastum
- External IDs
- B-9302-107
- B9302-107
- BY-217
- BY217
- BYK-20869
- BYK20869
Pharmacology
- Indication
Oral roflumilast is indicated to reduce the risk of COPD exacerbations in patients with severe COPD associated with chronic bronchitis and a history of exacerbations.9,12,13
The topical cream of roflumilast is indicated for the treatment of plaque psoriasis, including intertriginous areas, and mild to moderate atopic dermatitis in patients six years of age and older.16
The topical foam is approved for use in patients nine years of age and older to treat seborrheic dermatitis.14
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Treatment of Atopic dermatitis •••••••••••• ••••• Prevention of Exacerbation of copd •••••••••••• ••••••• •• •••••••••••• •• ••••• •••••• ••••••• ••••••••••• ••••••••• ••••••• •••••• Treatment of Psoriasis vulgaris (plaque psoriasis) •••••••••••• ••••• Treatment of Seborrheic dermatitis •••••••••••• •••••• ••••••••• •••••••• •••• - Contraindications & Blackbox Warnings
Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API- Pharmacodynamics
Roflumilast and its active metabolite, roflumilast N-oxide, increase cyclic adenosine-3′, 5′-monophosphate (cAMP) in affected cells by inhibiting PDE4. They are highly selective for PDE4 and are effectively inactive against PDEs 1, 2, 3, 5, and 7.7
- Mechanism of action
Roflumilast and its active metabolite (roflumilast N-oxide) are inhibitors of PDE4. Roflumilast and roflumilast N-oxide inhibition of PDE4 (a major cyclic 3′,5′-adenosine monophosphate (cyclic AMP) metabolizing enzyme) activity leads to accumulation of intracellular cyclic AMP. The specific mechanism(s) by which roflumilast exerts its therapeutic action is not well defined.14
Target Actions Organism AcAMP-specific 3',5'-cyclic phosphodiesterase 4 (PDE4) inhibitorHumans - Absorption
After a 500mcg dose, the bioavailability of roflumilast is about 80%.9 In the fasted state, maximum plasma concentrations are reached in 0.5 to 2 hours, while in the fed state, Cmax is reduced by 40%, Tmax is increased by one hour, and total absorption is unchanged.9
Applied topically, the mean systemic exposure for roflumilast and its N-oxide metabolite in adults was 72.7 ± 53.1 and 628 ± 648 h∙ng/mL, respectively.10 The mean systemic exposure for roflumilast and its N-oxide metabolite in adolescents was 25.1 ± 24.0 and 140 ± 179 h∙ng/mL, respectively.10
- Volume of distribution
Following a single oral dose of 500 mcg, the volume of distribution of roflumilast is approximately 2.9 L/kg.9
- Protein binding
Plasma protein binding of roflumilast and its N-oxide metabolite is approximately 99% and 97%, respectively.9
- Metabolism
Roflumilast is metabolized to roflumilast N-oxide, the active metabolite of roflumilast in humans, by CYP3A4 and CYP1A2.9 The N-oxide metabolite is less potent than its parent drug in regards to PDE4 inhibition, but its plasma AUC is approximately 10-fold greater.9
Hover over products below to view reaction partners
- Route of elimination
Roflumilast is excreted 70% in the urine as roflumilast N-oxide.8
- Half-life
Following oral administration, the plasma half-lives of roflumilast and roflumilast N-oxide are 17 hours and 30 hours, respectively.9
- Clearance
Plasma clearance of roflumilast following short-term intravenous infusion is approximately 9.6 L/h.9
- Adverse Effects
Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.- Toxicity
There are no data regarding overdosage with orally administered roflumilast. Phase I studies in which roflumilast was administered at single doses up to 5000 mcg showed an increase in the incidence of headache, gastrointestinal disorders, dizziness, palpitations, lightheadedness, clamminess, and arterial hypotension.9 In the event of an overdose, administer support medical care as soon as possible. Hemodialysis is unlikely to be of benefit given the extensive protein binding of roflumilast.9
- 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 softwareAbacavir Abacavir may decrease the excretion rate of Roflumilast which could result in a higher serum level. Abametapir The serum concentration of Roflumilast can be increased when it is combined with Abametapir. Abatacept Roflumilast may increase the immunosuppressive activities of Abatacept. Abemaciclib The metabolism of Abemaciclib can be decreased when combined with Roflumilast. Abiraterone The serum concentration of Roflumilast can be increased when it is combined with Abiraterone. - Food Interactions
- Take with or without food. Administering roflumilast with a high-fat meal reduced and delayed the Cmax and Tmax, respectively, but did not impact the AUC of roflumilast or its active metabolite (roflumilast N‐oxide).
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.- Product Images
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Daliresp Tablet, film coated 500 μg Oral Astrazeneca Ab 2024-07-10 2018-01-11 EU 
Daliresp Tablet 500 ug/1 Oral AstraZeneca Pharmaceuticals LP 2015-07-01 Not applicable US 
Daliresp Tablet, film coated 500 μg Oral Astrazeneca Ab 2024-07-10 2018-01-11 EU Daliresp Tablet 500 ug/1 Oral Allergan, Inc. 2011-02-28 2016-07-31 US Daliresp Tablet 250 ug/1 Oral AstraZeneca Pharmaceuticals LP 2015-07-01 Not applicable US - Generic Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Roflumilast Tablet 250 ug/1 Oral Camber Pharmaceuticals, Inc. 2023-04-18 Not applicable US Roflumilast Tablet 500 ug/1 Oral Micro Labs Limited 2022-10-19 Not applicable US Roflumilast Tablet 500 ug/1 Oral Zydus Lifesciences Limited 2022-10-03 Not applicable US Roflumilast Tablet 500 ug/1 Oral Solco Healthcare US, LLC 2022-05-10 Not applicable US Roflumilast Tablet 500 ug/1 Oral Major Pharmaceuticals 2022-09-07 Not applicable US
Categories
- ATC Codes
- D05AX06 — Roflumilast
- D05AX — Other antipsoriatics for topical use
- D05A — ANTIPSORIATICS FOR TOPICAL USE
- D05 — ANTIPSORIATICS
- D — DERMATOLOGICALS
- Drug Categories
- Acids, Carbocyclic
- Agents to Treat Airway Disease
- Amides
- Amines
- Antipsoriatics
- Antipsoriatics for Topical Use
- Benzene Derivatives
- Benzoates
- Cycloparaffins
- Cytochrome P-450 CYP1A2 Substrates
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 CYP3A4 Substrates (strength unknown)
- Cytochrome P-450 Substrates
- Dermatologicals
- Drugs for Obstructive Airway Diseases
- Drugs that are Mainly Renally Excreted
- Phosphodiesterase 4 Inhibitors
- Phosphodiesterase Inhibitors
- Pyridines
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as benzamides. These are organic compounds containing a carboxamido substituent attached to a benzene ring.
- Kingdom
- Organic compounds
- Super Class
- Benzenoids
- Class
- Benzene and substituted derivatives
- Sub Class
- Benzoic acids and derivatives
- Direct Parent
- Benzamides
- Alternative Parents
- Benzoyl derivatives / Phenol ethers / Phenoxy compounds / Polyhalopyridines / Alkyl aryl ethers / Aryl chlorides / Heteroaromatic compounds / Secondary carboxylic acid amides / Azacyclic compounds / Organopnictogen compounds show 6 more
- Substituents
- Alkyl aryl ether / Alkyl fluoride / Alkyl halide / Aromatic heteromonocyclic compound / Aryl chloride / Aryl halide / Azacycle / Benzamide / Benzoyl / Carboxamide group show 19 more
- Molecular Framework
- Aromatic heteromonocyclic compounds
- External Descriptors
- organofluorine compound, aromatic ether, benzamides, cyclopropanes, chloropyridine (CHEBI:47657)
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- 0P6C6ZOP5U
- CAS number
- 162401-32-3
- InChI Key
- MNDBXUUTURYVHR-UHFFFAOYSA-N
- InChI
- InChI=1S/C17H14Cl2F2N2O3/c18-11-6-22-7-12(19)15(11)23-16(24)10-3-4-13(26-17(20)21)14(5-10)25-8-9-1-2-9/h3-7,9,17H,1-2,8H2,(H,22,23,24)
- IUPAC Name
- 3-(cyclopropylmethoxy)-N-(3,5-dichloropyridin-4-yl)-4-(difluoromethoxy)benzamide
- SMILES
- FC(F)OC1=C(OCC2CC2)C=C(C=C1)C(=O)NC1=C(Cl)C=NC=C1Cl
References
- Synthesis Reference
王朝阳, 马静君, 郭培良, 黄耀宗, 王利春, 沈芃, 梁隆, & 程志鹏. (2015, March 25). Method for synthesizing roflumilast. CN103012256B.
- General References
- Meyers JA, Taverna J, Chaves J, Makkinje A, Lerner A: Phosphodiesterase 4 inhibitors augment levels of glucocorticoid receptor in B cell chronic lymphocytic leukemia but not in normal circulating hematopoietic cells. Clin Cancer Res. 2007 Aug 15;13(16):4920-7. [Article]
- Sanz MJ, Cortijo J, Taha MA, Cerda-Nicolas M, Schatton E, Burgbacher B, Klar J, Tenor H, Schudt C, Issekutz AC, Hatzelmann A, Morcillo EJ: Roflumilast inhibits leukocyte-endothelial cell interactions, expression of adhesion molecules and microvascular permeability. Br J Pharmacol. 2007 Oct;152(4):481-92. Epub 2007 Aug 20. [Article]
- Barone FC, Barton ME, White RF, Legos JJ, Kikkawa H, Shimamura M, Kuratani K, Kinoshita M: Inhibition of phosphodiesterase type 4 decreases stress-induced defecation in rats and mice. Pharmacology. 2008;81(1):11-7. Epub 2007 Aug 28. [Article]
- Chong J, Poole P, Leung B, Black PN: Phosphodiesterase 4 inhibitors for chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2011 May 11;(5):CD002309. doi: 10.1002/14651858.CD002309.pub3. [Article]
- Grootendorst DC, Gauw SA, Verhoosel RM, Sterk PJ, Hospers JJ, Bredenbroker D, Bethke TD, Hiemstra PS, Rabe KF: Reduction in sputum neutrophil and eosinophil numbers by the PDE4 inhibitor roflumilast in patients with COPD. Thorax. 2007 Dec;62(12):1081-7. Epub 2007 Jun 15. [Article]
- Thappali SR, Varanasi KV, Veeraraghavan S, Vakkalanka SK, Mukkanti K: Simultaneous quantitation of IC87114, roflumilast and its active metabolite roflumilast N-oxide in plasma by LC-MS/MS: application for a pharmacokinetic study. J Mass Spectrom. 2012 Dec;47(12):1612-9. doi: 10.1002/jms.3103. [Article]
- Giembycz MA, Field SK: Roflumilast: first phosphodiesterase 4 inhibitor approved for treatment of COPD. Drug Des Devel Ther. 2010 Jul 21;4:147-58. doi: 10.2147/dddt.s7667. [Article]
- Baye J: Roflumilast (daliresp): a novel phosphodiesterase-4 inhibitor for the treatment of severe chronic obstructive pulmonary disease. P T. 2012 Mar;37(3):149-61. [Article]
- FDA Approved Drug Products: Daliresp (roflumilast) tablets for oral use [Link]
- FDA Approved Drug Products: Zoryve (roflumilast) cream for topical use [Link]
- Arcutis Biotherapeutics: FDA Approves Arcutis’ ZORYVE™ (Roflumilast) Cream 0.3% For the Treatment of Plaque Psoriasis in Individuals Age 12 and Older [Link]
- Health Canada Approved Drug Products: ZORYVE (Roflumilast) Topical Cream [Link]
- EMA Approved Drug Products: DAXAS (roflumilast) Oral Tablets [Link]
- FDA Approved Drug Products: ZORYVE (roflumilast) topical foam, 0.3% (December 2023) [Link]
- FDA Approves Arcutis’ ZORYVE® (roflumilast) Topical Foam, 0.3% for the Treatment of Seborrheic Dermatitis in Individuals Aged 9 Years and Older [Link]
- FDA Approved Drug Products: ZORYVE (roflumilast) cream 0.3% and 0.15%, for topical use (July 2024) [Link]
- External Links
- Human Metabolome Database
- HMDB0257288
- KEGG Drug
- D05744
- PubChem Compound
- 449193
- PubChem Substance
- 175426853
- ChemSpider
- 395793
- BindingDB
- 14774
- 1091836
- ChEBI
- 47657
- ChEMBL
- CHEMBL193240
- ZINC
- ZINC000000592419
- PharmGKB
- PA165948052
- PDBe Ligand
- ROF
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Roflumilast
- PDB Entries
- 1xmu / 1xoq / 3g4l
- FDA label
- Download (255 KB)
- MSDS
- Download (569 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 Completed Not Available Chronic Obstructive Pulmonary Disease (COPD) 3 somestatus stop reason just information to hide Not Available Completed Not Available Severe COPD 1 somestatus stop reason just information to hide Not Available Completed Treatment Chronic Obstructive Pulmonary Disease (COPD) 1 somestatus stop reason just information to hide Not Available Unknown Status Not Available Alzheimer's Disease (AD) 1 somestatus stop reason just information to hide 4 Completed Not Available Chronic Obstructive Pulmonary Disease (COPD) 2 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Tablet Oral Tablet Oral 250 ug/1 Tablet Oral 500 ug/1 Tablet, film coated Oral 500 μg Tablet Oral 250 MCG Tablet Oral 250 ?g Tablet Oral 500 mcg Tablet, film coated Oral 500 mcg Tablet Oral 500.000 µg Tablet, film coated Oral Powder, for solution Oral Aerosol, foam Topical 3 mg/1g Cream Topical 0.3 % w/w Cream Topical 1.5 mg/1g Cream Topical 3 mg/1g Tablet, film coated Oral 0.5 mg - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US8536206 No 2013-09-17 2024-03-08 US US8604064 No 2013-12-10 2024-03-08 US US5712298 No 1998-01-27 2020-01-27 US US8618142 No 2013-12-31 2024-03-08 US US8431154 No 2013-04-30 2023-02-19 US US9468598 No 2016-10-18 2023-02-19 US US9907788 No 2018-03-06 2037-06-07 US US11129818 No 2021-09-28 2037-08-25 US US10940142 No 2021-03-09 2037-06-07 US US9884050 No 2018-02-06 2037-06-07 US US11793796 No 2017-06-07 2037-06-07 US US11819496 No 2017-06-07 2037-06-07 US US11707454 No 2021-12-03 2041-12-03 US US11992480 No 2017-06-07 2037-06-07 US US12005051 No 2017-06-07 2037-06-07 US US12011437 No 2017-06-07 2037-06-07 US US12016848 No 2017-06-07 2037-06-07 US US12005052 No 2017-06-07 2037-06-07 US US12042487 No 2017-06-07 2037-06-07 US
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 158 Giembycz MA, Field SK: Roflumilast: first phosphodiesterase 4 inhibitor approved for treatment of COPD. Drug Des Devel Ther. 2010 Jul 21;4:147-58. doi: 10.2147/dddt.s7667. water solubility Sparingly soluble Giembycz MA, Field SK: Roflumilast: first phosphodiesterase 4 inhibitor approved for treatment of COPD. Drug Des Devel Ther. 2010 Jul 21;4:147-58. doi: 10.2147/dddt.s7667. pKa 8.74 Not Available - Predicted Properties
Property Value Source Water Solubility 0.0062 mg/mL ALOGPS logP 4.47 ALOGPS logP 4.45 Chemaxon logS -4.8 ALOGPS pKa (Strongest Acidic) 13.3 Chemaxon pKa (Strongest Basic) 2.4 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 4 Chemaxon Hydrogen Donor Count 1 Chemaxon Polar Surface Area 60.45 Å2 Chemaxon Rotatable Bond Count 7 Chemaxon Refractivity 93.92 m3·mol-1 Chemaxon Polarizability 35.9 Å3 Chemaxon Number of Rings 3 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule Yes Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 1.0 Blood Brain Barrier + 0.9874 Caco-2 permeable + 0.5235 P-glycoprotein substrate Non-substrate 0.7295 P-glycoprotein inhibitor I Non-inhibitor 0.5775 P-glycoprotein inhibitor II Non-inhibitor 0.622 Renal organic cation transporter Non-inhibitor 0.8057 CYP450 2C9 substrate Non-substrate 0.8082 CYP450 2D6 substrate Non-substrate 0.7705 CYP450 3A4 substrate Substrate 0.5821 CYP450 1A2 substrate Inhibitor 0.7732 CYP450 2C9 inhibitor Inhibitor 0.5686 CYP450 2D6 inhibitor Non-inhibitor 0.7204 CYP450 2C19 inhibitor Inhibitor 0.7813 CYP450 3A4 inhibitor Inhibitor 0.6242 CYP450 inhibitory promiscuity High CYP Inhibitory Promiscuity 0.8602 Ames test Non AMES toxic 0.5216 Carcinogenicity Non-carcinogens 0.8843 Biodegradation Not ready biodegradable 1.0 Rat acute toxicity 2.3522 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9704 hERG inhibition (predictor II) Non-inhibitor 0.6336
Spectra
- Mass Spec (NIST)
- Download (81 KB)
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 176.61873 predictedDeepCCS 1.0 (2019) [M+H]+ 178.97672 predictedDeepCCS 1.0 (2019) [M+Na]+ 186.01021 predictedDeepCCS 1.0 (2019)
Targets
Build, predict & validate machine-learning models
Use our structured and evidence-based datasets to unlock newinsights and accelerate drug research.
Use our structured and evidence-based datasets to unlock new insights and accelerate drug research.
- Kind
- Protein group
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Hydrolyzes the second messenger 3',5'-cyclic AMP (cAMP), which is a key regulator of many important physiological processes
- Specific Function
- 3',5'-cyclic-AMP phosphodiesterase activity
Components:
| Name | UniProt ID |
|---|---|
| 3',5'-cyclic-AMP phosphodiesterase 4A | P27815 |
| 3',5'-cyclic-AMP phosphodiesterase 4B | Q07343 |
| 3',5'-cyclic-AMP phosphodiesterase 4C | Q08493 |
| 3',5'-cyclic-AMP phosphodiesterase 4D | Q08499 |
References
- Giembycz MA, Field SK: Roflumilast: first phosphodiesterase 4 inhibitor approved for treatment of COPD. Drug Des Devel Ther. 2010 Jul 21;4:147-58. doi: 10.2147/dddt.s7667. [Article]
- FDA Approved Drug Products: Daliresp (roflumilast) tablets for oral use [Link]
- FDA Approved Drug Products: Zoryve (roflumilast) cream for topical use [Link]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- 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
- Kelly Freeman ML: Clinical Considerations for Roflumilast: A New Treatment for COPD. Consult Pharm. 2012 Mar;27(3):189-93. doi: 10.4140/TCP.n.2012.189. [Article]
- Baye J: Roflumilast (daliresp): a novel phosphodiesterase-4 inhibitor for the treatment of severe chronic obstructive pulmonary disease. P T. 2012 Mar;37(3):149-61. [Article]
- Rabe KF: Update on roflumilast, a phosphodiesterase 4 inhibitor for the treatment of chronic obstructive pulmonary disease. Br J Pharmacol. 2011 May;163(1):53-67. doi: 10.1111/j.1476-5381.2011.01218.x. [Article]
- FDA Approved Drug Products: Daliresp (roflumilast) tablets for oral use [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids, steroid hormones and vitamins (PubMed:10681376, PubMed:11555828, PubMed:12865317, PubMed:19965576, PubMed:9435160). 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:10681376, PubMed:11555828, PubMed:12865317, PubMed:19965576, PubMed:9435160). Catalyzes the hydroxylation of carbon-hydrogen bonds (PubMed:11555828, PubMed:12865317). Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1) and 17beta-estradiol (E2), namely 2-hydroxy E1 and E2 (PubMed:11555828, PubMed:12865317). Metabolizes cholesterol toward 25-hydroxycholesterol, a physiological regulator of cellular cholesterol homeostasis (PubMed:21576599). May act as a major enzyme for all-trans retinoic acid biosynthesis in the liver. Catalyzes two successive oxidative transformation of all-trans retinol to all-trans retinal and then to the active form all-trans retinoic acid (PubMed:10681376). Primarily catalyzes stereoselective epoxidation of the last double bond of polyunsaturated fatty acids (PUFA), displaying a strong preference for the (R,S) stereoisomer (PubMed:19965576). Catalyzes bisallylic hydroxylation and omega-1 hydroxylation of PUFA (PubMed:9435160). May also participate in eicosanoids metabolism by converting hydroperoxide species into oxo metabolites (lipoxygenase-like reaction, NADPH-independent) (PubMed:21068195). Plays a role in the oxidative metabolism of xenobiotics. Catalyzes the N-hydroxylation of heterocyclic amines and the O-deethylation of phenacetin (PubMed:14725854). Metabolizes caffeine via N3-demethylation (Probable)
- Specific Function
- aromatase activity
- Gene Name
- CYP1A2
- Uniprot ID
- P05177
- Uniprot Name
- Cytochrome P450 1A2
- Molecular Weight
- 58406.915 Da
References
Drug created at June 13, 2005 13:24 / Updated at October 21, 2024 12:39