Flibanserin
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Identification
- Summary
Flibanserin is a 5-HT receptor modulator used for the treatment of selected premenopausal women with acquired, generalized hypoactive sexual desire disorder (HSDD).
- Brand Names
- Addyi
- Generic Name
- Flibanserin
- DrugBank Accession Number
- DB04908
- Background
Flibanserin is the first drug to be approved for hypoactive sexual desire disorder (HSDD) in premenopausal women by the FDA in August 2015. It was originally developed as an antidepressant medication by Boehringer Ingelheim, but showed lack of efficacy in trials and was further developed as a hypoactive sexual disorder drug by Sprout Pharmaceuticals. Flibanserin's mechanism of action is attributed to its high affinity for 5-HTA1 and 5-HTA2 receptors, displaying agonist activity on 5-HTA1 and antagonist on 5-HTA2, resulting in lowering of serotonin in the brain as well as an effect on increasing norepinephrine and dopamine neurotransmitters.
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
- Weight
- Average: 390.4021
Monoisotopic: 390.166745929 - Chemical Formula
- C20H21F3N4O
- Synonyms
- Flibanserin
- External IDs
- BIMT 17
- BIMT 17 BS
- BIMT-17
- BIMT-17-BS
Pharmacology
- Indication
For the treatment of hypoactive sexual desire disorder (HSDD) in premenopausal women.
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 Hypoactive sexual desire disorder •••••••••••• ••••••••••••• - Contraindications & Blackbox Warnings
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- Pharmacodynamics
Not Available
- Mechanism of action
Flibansetrin has high affinity for serotonin receptors in the brain: it acts as an agonist on 5-HT1A and an antagonist on 5-HT2A. In vivo, flibanserin binds equally to 5-HT1A and 5-HT2A receptors. However, under higher levels of brain 5-HT (i.e., under stress), flibanserin may occupy 5-HT2A receptors in higher proportion than 5-HT(1A) receptors. It may also moderately antagonize D4 (dopamine) receptors and 5-HT2B and 5-HTB2C. Its action on neurotransmitter receptors may contribute to reduction in serotonin levels and increase in dopamine and norepinephrine levels, all of which may play part in reward processing.
Target Actions Organism A5-hydroxytryptamine receptor 1A agonistHumans A5-hydroxytryptamine receptor 2A antagonistHumans AD(4) dopamine receptor antagonistagonistHumans - Absorption
Flibanserin has an absolute oral availability of 33%.
- Volume of distribution
Not Available
- Protein binding
~98%, highly bound to proteins (mostly albumin) in serum.
- Metabolism
Metabolism is primarily via CYP3A4, slightly CYP2C19. Minimal involvement of CYP1A2, CYP2B6, CYP2C8, CYP2C9 or CYP2D6. At least 35 metabolites of flibanserin are produced, 2 of which reach plasma concentrations as high as parent drug, however they are pharmacologically inactive.
- Route of elimination
Elimination via feces (51%) and urine (44%) following a single oral 50 mg dose of flibanserin solution.
- Half-life
≈11 hours
- Clearance
Not Available
- 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
Not Available
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
Interacting Gene/Enzyme Allele name Genotype(s) Defining Change(s) Type(s) Description Details Cytochrome P450 2C19 CYP2C19*2A Not Available 681G>A Effect Inferred Poor drug metabolizer. Details Cytochrome P450 2C19 CYP2C19*2B Not Available 681G>A Effect Inferred Poor drug metabolizer. Details Cytochrome P450 2C19 CYP2C19*3 Not Available 636G>A Effect Inferred Poor drug metabolizer. Details Cytochrome P450 2C19 CYP2C19*4 Not Available 1A>G Effect Inferred Poor drug metabolizer. Details Cytochrome P450 2C19 CYP2C19*5 Not Available 1297C>T Effect Inferred Poor drug metabolizer. Details Cytochrome P450 2C19 CYP2C19*6 Not Available 395G>A Effect Inferred Poor drug metabolizer. Details Cytochrome P450 2C19 CYP2C19*7 Not Available 19294T>A Effect Inferred Poor drug metabolizer. Details Cytochrome P450 2C19 CYP2C19*22 Not Available 557G>C / 991A>G Effect Inferred Poor drug metabolizer. Details Cytochrome P450 2C19 CYP2C19*24 Not Available 99C>T / 991A>G … show all Effect Inferred Poor drug metabolizer. Details Cytochrome P450 2C19 CYP2C19*35 Not Available 12662A>G Effect Inferred Poor drug metabolizer. Details
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 software1,2-Benzodiazepine The risk or severity of CNS depression can be increased when Flibanserin is combined with 1,2-Benzodiazepine. Abametapir The serum concentration of Flibanserin can be increased when it is combined with Abametapir. Abemaciclib The serum concentration of Abemaciclib can be increased when it is combined with Flibanserin. Acebutolol Flibanserin may decrease the antihypertensive activities of Acebutolol. Aceclofenac The risk or severity of hypertension can be increased when Flibanserin is combined with Aceclofenac. - Food Interactions
- Avoid alcohol. Avoid alcohol. Ingesting alcohol may increase the CNS depressant and hypotensive effects of flibanserin. If you have consumed two drinks, wait two hours before taking flibanserin. Do not take flibanserin if you have consumed more than three drinks.
- Avoid grapefruit products.
- Avoid St. John's Wort.
- Take with or without food. Taking flibanserin with food (especially a high-fat meal) may increase its AUC, Cmax, and Tmax.
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 Ingredients
Ingredient UNII CAS InChI Key Flibanserin hydrochloride 96XTC36K1B 147359-76-0 XGAGFLQFMFCIHZ-UHFFFAOYSA-N - International/Other Brands
- Ectris
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Addyi Tablet 100 mg Oral Searchlight Pharma Inc 2018-11-13 Not applicable Canada Addyi Tablet, film coated 100 mg/1 Oral Sprout Pharmaceuticals, Inc. 2015-08-18 Not applicable US
Categories
- ATC Codes
- G02CX02 — Flibanserin
- Drug Categories
- Agents that produce hypertension
- Antidepressive Agents
- Central Nervous System Depressants
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 Substrates
- Genito Urinary System and Sex Hormones
- Heterocyclic Compounds, Fused-Ring
- Miscellaneous Central Nervous System Agents
- P-glycoprotein inhibitors
- Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome
- Serotonin 5-HT1 Receptor Agonists
- Serotonin 5-HT2 Receptor Antagonists
- Serotonin 5-HT2A Receptor Antagonists
- Serotonin Agents
- Serotonin Modulators
- Serotonin Receptor Agonists
- Serotonin Receptor Antagonists
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as phenylpiperazines. These are compounds containing a phenylpiperazine skeleton, which consists of a piperazine bound to a phenyl group.
- Kingdom
- Organic compounds
- Super Class
- Organoheterocyclic compounds
- Class
- Diazinanes
- Sub Class
- Piperazines
- Direct Parent
- Phenylpiperazines
- Alternative Parents
- N-arylpiperazines / Trifluoromethylbenzenes / Benzimidazoles / Aniline and substituted anilines / Dialkylarylamines / N-alkylpiperazines / N-substituted imidazoles / Heteroaromatic compounds / Trialkylamines / Ureas show 7 more
- Substituents
- Alkyl fluoride / Alkyl halide / Amine / Aniline or substituted anilines / Aromatic heteropolycyclic compound / Azacycle / Azole / Benzenoid / Benzimidazole / Dialkylarylamine show 21 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- 37JK4STR6Z
- CAS number
- 167933-07-5
- InChI Key
- PPRRDFIXUUSXRA-UHFFFAOYSA-N
- InChI
- InChI=1S/C20H21F3N4O/c21-20(22,23)15-4-3-5-16(14-15)26-11-8-25(9-12-26)10-13-27-18-7-2-1-6-17(18)24-19(27)28/h1-7,14H,8-13H2,(H,24,28)
- IUPAC Name
- 1-(2-{4-[3-(trifluoromethyl)phenyl]piperazin-1-yl}ethyl)-2,3-dihydro-1H-1,3-benzodiazol-2-one
- SMILES
- FC(F)(F)C1=CC(=CC=C1)N1CCN(CCN2C(=O)NC3=CC=CC=C23)CC1
References
- General References
- Invernizzi RW, Sacchetti G, Parini S, Acconcia S, Samanin R: Flibanserin, a potential antidepressant drug, lowers 5-HT and raises dopamine and noradrenaline in the rat prefrontal cortex dialysate: role of 5-HT(1A) receptors. Br J Pharmacol. 2003 Aug;139(7):1281-8. [Article]
- Scandroglio A, Monferini E, Borsini F: Ex vivo binding of flibanserin to serotonin 5-HT1A and 5-HT2A receptors. Pharmacol Res. 2001 Feb;43(2):179-83. [Article]
- Borsini F, Cesana R: Mechanism of action of flibanserin in the learned helplessness paradigm in rats. Eur J Pharmacol. 2001 Dec 14;433(1):81-9. [Article]
- Borsini F, Evans K, Jason K, Rohde F, Alexander B, Pollentier S: Pharmacology of flibanserin. CNS Drug Rev. 2002 Summer;8(2):117-42. [Article]
- Deeks ED: Flibanserin: First Global Approval. Drugs. 2015 Oct;75(15):1815-22. doi: 10.1007/s40265-015-0474-y. [Article]
- Stahl SM: Mechanism of action of flibanserin, a multifunctional serotonin agonist and antagonist (MSAA), in hypoactive sexual desire disorder. CNS Spectr. 2015 Feb;20(1):1-6. doi: 10.1017/S1092852914000832. Epub 2015 Feb 9. [Article]
- FDA Approved Drug Products: ADDYI (flibanserin) tablets [Link]
- External Links
- KEGG Drug
- D02577
- PubChem Compound
- 6918248
- PubChem Substance
- 175426897
- ChemSpider
- 5293454
- BindingDB
- 50476735
- 1665509
- ChEBI
- 90865
- ChEMBL
- CHEMBL231068
- ZINC
- ZINC000052716421
- PharmGKB
- PA166153431
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Flibanserin
- FDA label
- Download (788 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 Breast Cancer / Hyposexual Desire Disorder 1 somestatus stop reason just information to hide Not Available Terminated Basic Science Hypoactive Sexual Desire Disorder (HSDD) 1 somestatus stop reason just information to hide 4 Terminated Treatment Hypoactive Sexual Desire Disorder (HSDD) 1 somestatus stop reason just information to hide 3 Completed Treatment Sexual Dysfunctions, Psychological 8 somestatus stop reason just information to hide 3 Terminated Treatment Depression / Sexual Dysfunctions, Psychological 1 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Tablet Oral 100 mg Tablet, film coated Oral 100 mg/1 - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US7151103 No 2006-12-19 2023-05-09 US US8227471 No 2012-07-24 2023-05-09 US US7420057 No 2008-09-02 2022-08-01 US US9468639 No 2016-10-18 2022-10-16 US
Properties
- State
- Solid
- Experimental Properties
- Not Available
- Predicted Properties
Property Value Source Water Solubility 0.178 mg/mL ALOGPS logP 3.32 ALOGPS logP 3.83 Chemaxon logS -3.3 ALOGPS pKa (Strongest Acidic) 12.91 Chemaxon pKa (Strongest Basic) 7.03 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 3 Chemaxon Hydrogen Donor Count 1 Chemaxon Polar Surface Area 38.82 Å2 Chemaxon Rotatable Bond Count 5 Chemaxon Refractivity 103.65 m3·mol-1 Chemaxon Polarizability 38.69 Å3 Chemaxon Number of Rings 4 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule Yes Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 1.0 Blood Brain Barrier + 0.9857 Caco-2 permeable - 0.7652 P-glycoprotein substrate Substrate 0.6865 P-glycoprotein inhibitor I Inhibitor 0.8895 P-glycoprotein inhibitor II Inhibitor 0.8741 Renal organic cation transporter Inhibitor 0.6378 CYP450 2C9 substrate Non-substrate 0.7906 CYP450 2D6 substrate Non-substrate 0.5905 CYP450 3A4 substrate Substrate 0.6954 CYP450 1A2 substrate Inhibitor 0.8379 CYP450 2C9 inhibitor Non-inhibitor 0.7028 CYP450 2D6 inhibitor Inhibitor 0.5876 CYP450 2C19 inhibitor Non-inhibitor 0.59 CYP450 3A4 inhibitor Inhibitor 0.7523 CYP450 inhibitory promiscuity High CYP Inhibitory Promiscuity 0.9005 Ames test Non AMES toxic 0.6798 Carcinogenicity Non-carcinogens 0.9354 Biodegradation Not ready biodegradable 1.0 Rat acute toxicity 2.6546 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.6138 hERG inhibition (predictor II) Inhibitor 0.9486
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-0006-0019000000-6fe6371d079641bb395a Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-0075-0009000000-c925d5782e731dde8e85 Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-0a4l-0059000000-848dff230616bb51300d Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-00y1-0109000000-00e36939a88eca6efa5b Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-02u3-1921000000-8ef4cee09370096944ab Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-01po-4932000000-8ea4feff344ed82f3dda Predicted 1H NMR Spectrum 1D NMR Not Applicable Predicted 13C NMR Spectrum 1D NMR Not Applicable - Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 184.70683 predictedDeepCCS 1.0 (2019) [M+H]+ 187.06483 predictedDeepCCS 1.0 (2019) [M+Na]+ 193.88432 predictedDeepCCS 1.0 (2019)
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Agonist
- General Function
- G-protein coupled receptor for 5-hydroxytryptamine (serotonin) (PubMed:22957663, PubMed:3138543, PubMed:33762731, PubMed:37935376, PubMed:37935377, PubMed:8138923, PubMed:8393041). Also functions as a receptor for various drugs and psychoactive substances (PubMed:22957663, PubMed:3138543, PubMed:33762731, PubMed:38552625, PubMed:8138923, PubMed:8393041). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of downstream effectors, such as adenylate cyclase (PubMed:22957663, PubMed:3138543, PubMed:33762731, PubMed:8138923, PubMed:8393041). HTR1A is coupled to G(i)/G(o) G alpha proteins and mediates inhibitory neurotransmission: signaling inhibits adenylate cyclase activity and activates a phosphatidylinositol-calcium second messenger system that regulates the release of Ca(2+) ions from intracellular stores (PubMed:33762731, PubMed:35610220). Beta-arrestin family members regulate signaling by mediating both receptor desensitization and resensitization processes (PubMed:18476671, PubMed:20363322, PubMed:20945968). Plays a role in the regulation of 5-hydroxytryptamine release and in the regulation of dopamine and 5-hydroxytryptamine metabolism (PubMed:18476671, PubMed:20363322, PubMed:20945968). Plays a role in the regulation of dopamine and 5-hydroxytryptamine levels in the brain, and thereby affects neural activity, mood and behavior (PubMed:18476671, PubMed:20363322, PubMed:20945968). Plays a role in the response to anxiogenic stimuli (PubMed:18476671, PubMed:20363322, PubMed:20945968)
- Specific Function
- G protein-coupled serotonin receptor activity
- Gene Name
- HTR1A
- Uniprot ID
- P08908
- Uniprot Name
- 5-hydroxytryptamine receptor 1A
- Molecular Weight
- 46106.335 Da
References
- Invernizzi RW, Sacchetti G, Parini S, Acconcia S, Samanin R: Flibanserin, a potential antidepressant drug, lowers 5-HT and raises dopamine and noradrenaline in the rat prefrontal cortex dialysate: role of 5-HT(1A) receptors. Br J Pharmacol. 2003 Aug;139(7):1281-8. [Article]
- Borsini F, Evans K, Jason K, Rohde F, Alexander B, Pollentier S: Pharmacology of flibanserin. CNS Drug Rev. 2002 Summer;8(2):117-42. [Article]
- Deeks ED: Flibanserin: First Global Approval. Drugs. 2015 Oct;75(15):1815-22. doi: 10.1007/s40265-015-0474-y. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Antagonist
- General Function
- G-protein coupled receptor for 5-hydroxytryptamine (serotonin) (PubMed:1330647, PubMed:18703043, PubMed:19057895, PubMed:21645528, PubMed:22300836, PubMed:35084960, PubMed:38552625). Also functions as a receptor for various drugs and psychoactive substances, including mescaline, psilocybin, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) and lysergic acid diethylamide (LSD) (PubMed:28129538, PubMed:35084960). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of downstream effectors (PubMed:28129538, PubMed:35084960). HTR2A is coupled to G(q)/G(11) G alpha proteins and activates phospholipase C-beta, releasing diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) second messengers that modulate the activity of phosphatidylinositol 3-kinase and promote the release of Ca(2+) ions from intracellular stores, respectively (PubMed:18703043, PubMed:28129538, PubMed:35084960). Beta-arrestin family members inhibit signaling via G proteins and mediate activation of alternative signaling pathways (PubMed:28129538, PubMed:35084960). Affects neural activity, perception, cognition and mood (PubMed:18297054). Plays a role in the regulation of behavior, including responses to anxiogenic situations and psychoactive substances. Plays a role in intestinal smooth muscle contraction, and may play a role in arterial vasoconstriction (By similarity)
- Specific Function
- 1-(4-iodo-2,5-dimethoxyphenyl)propan-2-amine binding
- Gene Name
- HTR2A
- Uniprot ID
- P28223
- Uniprot Name
- 5-hydroxytryptamine receptor 2A
- Molecular Weight
- 52602.58 Da
References
- Borsini F, Evans K, Jason K, Rohde F, Alexander B, Pollentier S: Pharmacology of flibanserin. CNS Drug Rev. 2002 Summer;8(2):117-42. [Article]
- Invernizzi RW, Sacchetti G, Parini S, Acconcia S, Samanin R: Flibanserin, a potential antidepressant drug, lowers 5-HT and raises dopamine and noradrenaline in the rat prefrontal cortex dialysate: role of 5-HT(1A) receptors. Br J Pharmacol. 2003 Aug;139(7):1281-8. [Article]
- Deeks ED: Flibanserin: First Global Approval. Drugs. 2015 Oct;75(15):1815-22. doi: 10.1007/s40265-015-0474-y. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- AntagonistAgonist
- General Function
- Dopamine receptor responsible for neuronal signaling in the mesolimbic system of the brain, an area of the brain that regulates emotion and complex behavior. Activated by dopamine, but also by epinephrine and norepinephrine, and by numerous synthetic agonists and drugs (PubMed:16423344, PubMed:27659709, PubMed:29051383, PubMed:9003072). Agonist binding triggers signaling via G proteins that inhibit adenylyl cyclase (PubMed:16423344, PubMed:27659709, PubMed:29051383, PubMed:7512953, PubMed:7643093). Modulates the circadian rhythm of contrast sensitivity by regulating the rhythmic expression of NPAS2 in the retinal ganglion cells (By similarity)
- Specific Function
- dopamine binding
- Gene Name
- DRD4
- Uniprot ID
- P21917
- Uniprot Name
- D(4) dopamine receptor
- Molecular Weight
- 43900.84 Da
References
- Borsini F, Evans K, Jason K, Rohde F, Alexander B, Pollentier S: Pharmacology of flibanserin. CNS Drug Rev. 2002 Summer;8(2):117-42. [Article]
- Invernizzi RW, Sacchetti G, Parini S, Acconcia S, Samanin R: Flibanserin, a potential antidepressant drug, lowers 5-HT and raises dopamine and noradrenaline in the rat prefrontal cortex dialysate: role of 5-HT(1A) receptors. Br J Pharmacol. 2003 Aug;139(7):1281-8. [Article]
- Deeks ED: Flibanserin: First Global Approval. Drugs. 2015 Oct;75(15):1815-22. doi: 10.1007/s40265-015-0474-y. [Article]
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
- Deeks ED: Flibanserin: First Global Approval. Drugs. 2015 Oct;75(15):1815-22. doi: 10.1007/s40265-015-0474-y. [Article]
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- 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
Drug created at October 21, 2007 22:23 / Updated at June 02, 2024 21:55