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Identification
- Summary
Flutamide is an antiandrogen used for locally confined stage B2-C and D-2 metastatic prostate carcinoma.
- Brand Names
- Eulexin
- Generic Name
- Flutamide
- DrugBank Accession Number
- DB00499
- Background
An antiandrogen with about the same potency as cyproterone in rodent and canine species.
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
Structure for Flutamide (DB00499)
- Weight
- Average: 276.2118
Monoisotopic: 276.072176843 - Chemical Formula
- C11H11F3N2O3
- Synonyms
- 4'-nitro-3'-trifluoromethylisobutyranilide
- Flutamid
- Flutamida
- Flutamide
- Flutamidum
- FTA
- NFBA
- Niftolid
- Niftolide
- α,α,α-trifluoro-2-methyl-4'-nitro-m-propionotoluidide
- External IDs
- SCH 13521
- SCH-13521
Pharmacology
- Indication
For the management of locally confined Stage B2-C and Stage D2 metastatic carcinoma of the prostate
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Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Used in combination to treat Stage b2-c metastatic carcinoma of the prostate •••••••••••• •••••••• •••••• Used in combination to treat Stage d2 metastatic carcinoma of the prostate •••••••••••• •••••••• •••••• - Contraindications & Blackbox Warnings
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Flutamide is a nonsteroidal antiandrogen. In animal studies, flutamide demonstrates potent antiandrogenic effects. It exerts its antiandrogenic action by inhibiting androgen uptake and/or by inhibiting nuclear binding of androgen in target tissues or both. Prostatic carcinoma is known to be androgen-sensitive and responds to treatment that counteracts the effect of androgen and/or removes the source of androgen, e.g. castration. Elevations of plasma testosterone and estradiol levels have been noted following flutamide administration.
- Mechanism of action
Flutamide is a nonsteroidal antiandrogen that blocks the action of both endogenous and exogenous testosterone by binding to the androgen receptor. In addition Flutamide is a potent inhibitor of testosterone-stimulated prostatic DNA synthesis. Moreover, it is capable of inhibiting prostatic nuclear uptake of androgen.
Target Actions Organism AAndrogen receptor antagonistHumans UAryl hydrocarbon receptor agonistHumans UNuclear receptor subfamily 1 group I member 2 Not Available Humans - Absorption
Rapidly and completely absorbed.
- Volume of distribution
Not Available
- Protein binding
94-96%
- Metabolism
Flutamide is rapidly and extensively metabolized, with flutamide comprising only 2.5% of plasma radioactivity 1 hour after administration.
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- Route of elimination
Flutamide and its metabolites are excreted mainly in the urine with only 4.2% of a single dose excreted in the feces over 72 hours.
- Half-life
The plasma half-life for the alpha-hydroxylated metabolite of flutamide (an active metabolite) is approximately 6 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
In animal studies with flutamide alone, signs of overdose included hypoactivity, piloerection, slow respiration, ataxia, and/or lacrimation, anorexia, tranquilization, emesis, and methemoglobinemia.
- 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 Flutamide may decrease the excretion rate of Abacavir which could result in a higher serum level. Abametapir The serum concentration of Flutamide can be increased when it is combined with Abametapir. Abatacept The metabolism of Flutamide can be increased when combined with Abatacept. Abiraterone The serum concentration of Flutamide can be increased when it is combined with Abiraterone. Acalabrutinib The metabolism of Flutamide can be decreased when combined with Acalabrutinib. - Food Interactions
- Take with or without food. The absorption is unaffected by food.
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
- International/Other Brands
- Andraxan (CSC) / Antipros (Medicamerc) / Curestat (Advanced Pharmaceutical) / Cytomid (Cipla) / Dedile (Ivax) / Drogenil (Bayer) / Elbat (Genepharm) / Etaconil (Nolver) / Farostat (Orion) / Flimutal (Cryopharma) / Flucinom (Merck Sharp & Dohme) / Flulem (Teva) / Odyne (Nippon Kayaku) / Prostadirex (Sanofi-Aventis) / Prostanon (Pharmachemie)
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Euflex Tablet 250 mg Oral Merck Ltd. 1984-12-31 2015-06-01 Canada 
Eulexin Capsule 125 mg/1 Oral Merck Sharp & Dohme Limited 1989-01-27 2005-09-30 US 
Flutamide Tablet 250 mg Oral Pharmel Inc 1998-12-01 2016-10-25 Canada Flutamide Tablet 250 mg Oral Pharmascience Inc 1997-10-31 2016-10-28 Canada Flutamide Tablet 250 mg Oral Schering Plough 1996-12-31 2014-07-31 Canada - Generic Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Dom-flutamide Tablet 250 mg / tab Oral Dominion Pharmacal Not applicable Not applicable Canada Eulexin Capsule 125 mg/1 Oral Waylis Therapeutics LLC 2021-11-12 Not applicable US Flutamide Capsule 125 mg/1 Oral Actavis Pharma, Inc. 2011-07-28 2020-02-29 US Flutamide Capsule 125 mg/1 Oral Genpharm Ulc 2015-11-01 2015-11-30 US Flutamide Capsule 125 mg/1 Oral Eon Labs, Inc. 2001-09-18 2011-08-31 US
Categories
- ATC Codes
- L02BB01 — Flutamide
- Drug Categories
- Amides
- Amines
- Androgen Receptor Antagonists
- Androgen Receptor Inhibitors
- Anilides
- Aniline Compounds
- Antiandrogens
- Antiandrogens, non-steroidal
- Antineoplastic Agents
- Antineoplastic Agents, Hormonal
- Antineoplastic and Immunomodulating Agents
- Cytochrome P-450 CYP1A2 Substrates
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 CYP3A5 Substrates
- Cytochrome P-450 Substrates
- Drugs that are Mainly Renally Excreted
- Endocrine Therapy
- Hormone Antagonists
- Hormone Antagonists and Related Agents
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Methemoglobinemia Associated Agents
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as trifluoromethylbenzenes. These are organofluorine compounds that contain a benzene ring substituted with one or more trifluoromethyl groups.
- Kingdom
- Organic compounds
- Super Class
- Benzenoids
- Class
- Benzene and substituted derivatives
- Sub Class
- Trifluoromethylbenzenes
- Direct Parent
- Trifluoromethylbenzenes
- Alternative Parents
- Nitrobenzenes / Anilides / Nitroaromatic compounds / N-arylamides / Secondary carboxylic acid amides / Propargyl-type 1,3-dipolar organic compounds / Organic oxoazanium compounds / Organopnictogen compounds / Organofluorides / Organic zwitterions show 4 more
- Substituents
- Alkyl fluoride / Alkyl halide / Allyl-type 1,3-dipolar organic compound / Anilide / Aromatic homomonocyclic compound / C-nitro compound / Carbonyl group / Carboxamide group / Carboxylic acid derivative / Hydrocarbon derivative show 18 more
- Molecular Framework
- Aromatic homomonocyclic compounds
- External Descriptors
- monocarboxylic acid amide, (trifluoromethyl)benzenes (CHEBI:5132)
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- 76W6J0943E
- CAS number
- 13311-84-7
- InChI Key
- MKXKFYHWDHIYRV-UHFFFAOYSA-N
- InChI
- InChI=1S/C11H11F3N2O3/c1-6(2)10(17)15-7-3-4-9(16(18)19)8(5-7)11(12,13)14/h3-6H,1-2H3,(H,15,17)
- IUPAC Name
- 2-methyl-N-[4-nitro-3-(trifluoromethyl)phenyl]propanamide
- SMILES
- CC(C)C(=O)NC1=CC(=C(C=C1)[N+]([O-])=O)C(F)(F)F
References
- Synthesis Reference
Jack Lawrence James, Louis Frank Molnar, Jr., Tania E. Toney-Parker, "Processes for preparing flutamide compounds and compounds prepared by such processes." U.S. Patent US 6,228,401, issued November, 1976.
US6228401- General References
- External Links
- Human Metabolome Database
- HMDB0014642
- KEGG Drug
- D00586
- KEGG Compound
- C07653
- PubChem Compound
- 3397
- PubChem Substance
- 46508874
- ChemSpider
- 3280
- BindingDB
- 50131270
- 4508
- ChEBI
- 5132
- ChEMBL
- CHEMBL806
- ZINC
- ZINC000003812944
- Therapeutic Targets Database
- DAP000301
- PharmGKB
- PA449685
- PDBe Ligand
- HFT
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- PDRhealth
- PDRhealth Drug Page
- Wikipedia
- Flutamide
- FDA label
- Download (413 KB)
- MSDS
- Download (55.8 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 Polycystic Ovarian Syndrome (PCOS) / Syndrome, Metabolic 1 somestatus stop reason just information to hide Not Available Completed Treatment Acne Vulgaris Superficial Mixed Comedonal and Inflammatory 1 somestatus stop reason just information to hide Not Available Terminated Basic Science Hyperandrogenism / Polycystic Ovarian Syndrome (PCOS) 1 somestatus stop reason just information to hide Not Available Terminated Health Services Research Polycystic Ovarian Syndrome (PCOS) 1 somestatus stop reason just information to hide 4 Completed Treatment Congenital Adrenal Hyperplasia (CAH) 1 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Schering corp sub schering plough corp
- Genpharm inc
- Ivax pharmaceuticals inc sub teva pharmaceuticals usa
- Par pharmaceutical inc
- Sandoz inc
- Watson laboratories inc
- Packagers
- Barr Pharmaceuticals
- Cipla Ltd.
- Eon Labs
- Ivax Pharmaceuticals
- Neuman Distributors Inc.
- Par Pharmaceuticals
- Pharmaceutical Utilization Management Program VA Inc.
- Physicians Total Care Inc.
- Salutas Pharma GmbH
- Sandhills Packaging Inc.
- Teva Pharmaceutical Industries Ltd.
- Watson Pharmaceuticals
- Dosage Forms
Form Route Strength Capsule Oral Tablet Oral Tablet Oral 250 mg Capsule Oral 125 mg/1 Tablet, film coated Oral Tablet, film coated Oral 250 MG Tablet Oral 250 mg / tab Tablet Oral 250.000 mg Tablet, coated - Prices
Unit description Cost Unit Flutamide 125 mg capsule 2.12USD capsule DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 111.5-112.5 Gold, E.H.; U.S. Patent 3,847,988; November 12, 1974; assigned to Schering Corp. water solubility 9.45 mg/L Not Available logP 3.35 MORRIS,JJ ET AL. (1991) - Predicted Properties
Property Value Source Water Solubility 0.00566 mg/mL ALOGPS logP 2.55 ALOGPS logP 3.27 Chemaxon logS -4.7 ALOGPS pKa (Strongest Acidic) 12.81 Chemaxon pKa (Strongest Basic) -3.7 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 3 Chemaxon Hydrogen Donor Count 1 Chemaxon Polar Surface Area 72.24 Å2 Chemaxon Rotatable Bond Count 4 Chemaxon Refractivity 62.42 m3·mol-1 Chemaxon Polarizability 23.22 Å3 Chemaxon Number of Rings 1 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
Property Value Probability Human Intestinal Absorption + 0.9948 Blood Brain Barrier + 0.9655 Caco-2 permeable + 0.7533 P-glycoprotein substrate Non-substrate 0.8131 P-glycoprotein inhibitor I Non-inhibitor 0.8254 P-glycoprotein inhibitor II Non-inhibitor 0.9428 Renal organic cation transporter Non-inhibitor 0.9535 CYP450 2C9 substrate Non-substrate 0.7927 CYP450 2D6 substrate Non-substrate 0.8935 CYP450 3A4 substrate Substrate 0.568 CYP450 1A2 substrate Inhibitor 0.9108 CYP450 2C9 inhibitor Non-inhibitor 0.6306 CYP450 2D6 inhibitor Non-inhibitor 0.9231 CYP450 2C19 inhibitor Inhibitor 0.8994 CYP450 3A4 inhibitor Non-inhibitor 0.5924 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.6574 Ames test Non AMES toxic 0.5728 Carcinogenicity Carcinogens 0.6077 Biodegradation Not ready biodegradable 0.9924 Rat acute toxicity 2.5770 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9881 hERG inhibition (predictor II) Non-inhibitor 0.8734
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 162.0618379 predictedDarkChem Lite v0.1.0 [M-H]- 152.5649147 predictedDarkChem Lite v0.1.0 [M-H]- 161.15562 predictedDeepCCS 1.0 (2019) [M+H]+ 163.3105379 predictedDarkChem Lite v0.1.0 [M+H]+ 149.7290801 predictedDarkChem Lite v0.1.0 [M+H]+ 163.90152 predictedDeepCCS 1.0 (2019) [M+Na]+ 162.2643379 predictedDarkChem Lite v0.1.0 [M+Na]+ 162.5492379 predictedDarkChem Lite v0.1.0 [M+Na]+ 172.15407 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.
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- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Antagonist
- General Function
- Steroid hormone receptors are ligand-activated transcription factors that regulate eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues (PubMed:19022849). Transcription factor activity is modulated by bound coactivator and corepressor proteins like ZBTB7A that recruits NCOR1 and NCOR2 to the androgen response elements/ARE on target genes, negatively regulating androgen receptor signaling and androgen-induced cell proliferation (PubMed:20812024). Transcription activation is also down-regulated by NR0B2. Activated, but not phosphorylated, by HIPK3 and ZIPK/DAPK3
- Specific Function
- Androgen binding
- Gene Name
- AR
- Uniprot ID
- P10275
- Uniprot Name
- Androgen receptor
- Molecular Weight
- 99187.115 Da
References
- Chang HC, Miyamoto H, Marwah P, Lardy H, Yeh S, Huang KE, Chang C: Suppression of Delta(5)-androstenediol-induced androgen receptor transactivation by selective steroids in human prostate cancer cells. Proc Natl Acad Sci U S A. 1999 Sep 28;96(20):11173-7. [Article]
- Martelli A, Campart GB, Carrozzino R, Ghia M, Mattioli F, Mereto E, Orsi P, Puglia CP: Evaluation of flutamide genotoxicity in rats and in primary human hepatocytes. Pharmacol Toxicol. 2000 Mar;86(3):129-34. [Article]
- Montalvo L, Carmena MJ, Solano RM, Clemente C, Roman ID, Sanchez-Chapado M, Prieto JC: Effect of flutamide-induced androgen-receptor blockade on adenylate cyclase activation through G-protein coupled receptors in rat prostate. Cell Signal. 2000 May;12(5):311-6. [Article]
- Pazos F, Sanchez-Franco F, Balsa JA, Escalada J, Palacios N, Cacicedo L: Mechanisms of reduced body growth in the pubertal feminized male rat: unbalanced estrogen and androgen action on the somatotropic axis. Pediatr Res. 2000 Jul;48(1):96-103. [Article]
- Shilling AD, Williams DE: The non-aromatizable androgen, dihydrotestosterone, induces antiestrogenic responses in the rainbow trout. J Steroid Biochem Mol Biol. 2000 Nov 15;74(4):187-94. [Article]
- Balk SP: Androgen receptor as a target in androgen-independent prostate cancer. Urology. 2002 Sep;60(3 Suppl 1):132-8; discussion 138-9. [Article]
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
- Zhou Y, Zhang Y, Zhao D, Yu X, Shen X, Zhou Y, Wang S, Qiu Y, Chen Y, Zhu F: TTD: Therapeutic Target Database describing target druggability information. Nucleic Acids Res. 2024 Jan 5;52(D1):D1465-D1477. doi: 10.1093/nar/gkad751. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Agonist
- General Function
- Ligand-activated transcription factor that enables cells to adapt to changing conditions by sensing compounds from the environment, diet, microbiome and cellular metabolism, and which plays important roles in development, immunity and cancer (PubMed:23275542, PubMed:30373764, PubMed:32818467, PubMed:7961644). Upon ligand binding, translocates into the nucleus, where it heterodimerizes with ARNT and induces transcription by binding to xenobiotic response elements (XRE) (PubMed:23275542, PubMed:30373764, PubMed:7961644). Regulates a variety of biological processes, including angiogenesis, hematopoiesis, drug and lipid metabolism, cell motility and immune modulation (PubMed:12213388). Xenobiotics can act as ligands: upon xenobiotic-binding, activates the expression of multiple phase I and II xenobiotic chemical metabolizing enzyme genes (such as the CYP1A1 gene) (PubMed:7961644). Mediates biochemical and toxic effects of halogenated aromatic hydrocarbons (PubMed:34521881, PubMed:7961644). Next to xenobiotics, natural ligands derived from plants, microbiota, and endogenous metabolism are potent AHR agonists (PubMed:18076143). Tryptophan (Trp) derivatives constitute an important class of endogenous AHR ligands (PubMed:32818467, PubMed:32866000). Acts as a negative regulator of anti-tumor immunity: indoles and kynurenic acid generated by Trp catabolism act as ligand and activate AHR, thereby promoting AHR-driven cancer cell motility and suppressing adaptive immunity (PubMed:32818467). Regulates the circadian clock by inhibiting the basal and circadian expression of the core circadian component PER1 (PubMed:28602820). Inhibits PER1 by repressing the CLOCK-BMAL1 heterodimer mediated transcriptional activation of PER1 (PubMed:28602820). The heterodimer ARNT:AHR binds to core DNA sequence 5'-TGCGTG-3' within the dioxin response element (DRE) of target gene promoters and activates their transcription (PubMed:28602820)
- Specific Function
- Cis-regulatory region sequence-specific dna binding
- Gene Name
- AHR
- Uniprot ID
- P35869
- Uniprot Name
- Aryl hydrocarbon receptor
- Molecular Weight
- 96146.705 Da
References
- Hu W, Sorrentino C, Denison MS, Kolaja K, Fielden MR: Induction of cyp1a1 is a nonspecific biomarker of aryl hydrocarbon receptor activation: results of large scale screening of pharmaceuticals and toxicants in vivo and in vitro. Mol Pharmacol. 2007 Jun;71(6):1475-86. Epub 2007 Feb 27. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Nuclear receptor that binds and is activated by variety of endogenous and xenobiotic compounds. Transcription factor that activates the transcription of multiple genes involved in the metabolism and secretion of potentially harmful xenobiotics, drugs and endogenous compounds. Activated by the antibiotic rifampicin and various plant metabolites, such as hyperforin, guggulipid, colupulone, and isoflavones. Response to specific ligands is species-specific. Activated by naturally occurring steroids, such as pregnenolone and progesterone. Binds to a response element in the promoters of the CYP3A4 and ABCB1/MDR1 genes
- Specific Function
- Dna-binding transcription activator activity, rna polymerase ii-specific
- Gene Name
- NR1I2
- Uniprot ID
- O75469
- Uniprot Name
- Nuclear receptor subfamily 1 group I member 2
- Molecular Weight
- 49761.245 Da
References
- Harmsen S, Meijerman I, Beijnen JH, Schellens JH: Nuclear receptor mediated induction of cytochrome P450 3A4 by anticancer drugs: a key role for the pregnane X receptor. Cancer Chemother Pharmacol. 2009 Jun;64(1):35-43. doi: 10.1007/s00280-008-0842-3. Epub 2008 Oct 7. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- 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:14559847, PubMed:15041462, PubMed:15805301, PubMed:18577768, PubMed:19965576, PubMed:20972997). 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:14559847, PubMed:15041462, PubMed:15805301, PubMed:18577768, PubMed:19965576, PubMed:20972997). Catalyzes the hydroxylation of carbon-hydrogen bonds. 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 C15-alpha and C16-alpha positions (PubMed:11555828, PubMed:12865317, PubMed:14559847, PubMed:15805301). Displays different regioselectivities for polyunsaturated fatty acids (PUFA) hydroxylation (PubMed:15041462, PubMed:18577768). Catalyzes the epoxidation of double bonds of certain PUFA (PubMed:15041462, PubMed:19965576, PubMed:20972997). Converts arachidonic acid toward epoxyeicosatrienoic acid (EET) regioisomers, 8,9-, 11,12-, and 14,15-EET, that function as lipid mediators in the vascular system (PubMed:20972997). Displays an absolute stereoselectivity in the epoxidation of eicosapentaenoic acid (EPA) producing the 17(R),18(S) enantiomer (PubMed:15041462). May play an important role in all-trans retinoic acid biosynthesis in extrahepatic tissues. 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). May also participate in eicosanoids metabolism by converting hydroperoxide species into oxo metabolites (lipoxygenase-like reaction, NADPH-independent) (PubMed:21068195)
- Specific Function
- Arachidonic acid monooxygenase activity
- Gene Name
- CYP1A1
- Uniprot ID
- P04798
- Uniprot Name
- Cytochrome P450 1A1
- Molecular Weight
- 58164.815 Da
References
- Rochat B, Morsman JM, Murray GI, Figg WD, McLeod HL: Human CYP1B1 and anticancer agent metabolism: mechanism for tumor-specific drug inactivation? J Pharmacol Exp Ther. 2001 Feb;296(2):537-41. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- 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:15258110, PubMed:20972997). 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:15258110, PubMed:20972997). Exhibits catalytic activity for the formation of hydroxyestrogens from estrone (E1) and 17beta-estradiol (E2), namely 2- and 4-hydroxy E1 and E2. Displays a predominant hydroxylase activity toward E2 at the C-4 position (PubMed:11555828, PubMed:12865317). Metabolizes testosterone and progesterone to B or D ring hydroxylated metabolites (PubMed:10426814). May act as a major enzyme for all-trans retinoic acid biosynthesis in extrahepatic tissues. 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, PubMed:15258110). Catalyzes the epoxidation of double bonds of certain PUFA. Converts arachidonic acid toward epoxyeicosatrienoic acid (EpETrE) regioisomers, 8,9-, 11,12-, and 14,15- EpETrE, that function as lipid mediators in the vascular system (PubMed:20972997). Additionally, displays dehydratase activity toward oxygenated eicosanoids hydroperoxyeicosatetraenoates (HpETEs). This activity is independent of cytochrome P450 reductase, NADPH, and O2 (PubMed:21068195). Also involved in the oxidative metabolism of xenobiotics, particularly converting polycyclic aromatic hydrocarbons and heterocyclic aryl amines procarcinogens to DNA-damaging products (PubMed:10426814). Plays an important role in retinal vascular development. Under hyperoxic O2 conditions, promotes retinal angiogenesis and capillary morphogenesis, likely by metabolizing the oxygenated products generated during the oxidative stress. Also, contributes to oxidative homeostasis and ultrastructural organization and function of trabecular meshwork tissue through modulation of POSTN expression (By similarity)
- Specific Function
- Aromatase activity
- Gene Name
- CYP1B1
- Uniprot ID
- Q16678
- Uniprot Name
- Cytochrome P450 1B1
- Molecular Weight
- 60845.33 Da
References
- Rochat B, Morsman JM, Murray GI, Figg WD, McLeod HL: Human CYP1B1 and anticancer agent metabolism: mechanism for tumor-specific drug inactivation? J Pharmacol Exp Ther. 2001 Feb;296(2):537-41. [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 (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
- Kang P, Dalvie D, Smith E, Zhou S, Deese A: Identification of a novel glutathione conjugate of flutamide in incubations with human liver microsomes. Drug Metab Dispos. 2007 Jul;35(7):1081-8. doi: 10.1124/dmd.107.014860. Epub 2007 Apr 2. [Article]
- Shet MS, McPhaul M, Fisher CW, Stallings NR, Estabrook RW: Metabolism of the antiandrogenic drug (Flutamide) by human CYP1A2. Drug Metab Dispos. 1997 Nov;25(11):1298-303. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- 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
- Wang B, Zhou SF: Synthetic and natural compounds that interact with human cytochrome P450 1A2 and implications in drug development. Curr Med Chem. 2009;16(31):4066-218. [Article]
- Shet MS, McPhaul M, Fisher CW, Stallings NR, Estabrook RW: Metabolism of the antiandrogenic drug (Flutamide) by human CYP1A2. Drug Metab Dispos. 1997 Nov;25(11):1298-303. [Article]
- Blobaum AL, Byers FW, Bridges TM, Locuson CW, Conn PJ, Lindsley CW, Daniels JS: A Screen of Approved Drugs Identifies the Androgen Receptor Antagonist Flutamide and Its Pharmacologically Active Metabolite 2-Hydroxy-Flutamide as Heterotropic Activators of Cytochrome P450 3A In Vitro and In Vivo. Drug Metab Dispos. 2015 Nov;43(11):1718-26. doi: 10.1124/dmd.115.064006. Epub 2015 Aug 11. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- 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
- Kang P, Dalvie D, Smith E, Zhou S, Deese A: Identification of a novel glutathione conjugate of flutamide in incubations with human liver microsomes. Drug Metab Dispos. 2007 Jul;35(7):1081-8. doi: 10.1124/dmd.107.014860. Epub 2007 Apr 2. [Article]
- Shet MS, McPhaul M, Fisher CW, Stallings NR, Estabrook RW: Metabolism of the antiandrogenic drug (Flutamide) by human CYP1A2. Drug Metab Dispos. 1997 Nov;25(11):1298-303. [Article]
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Mediates export of organic anions and drugs from the cytoplasm (PubMed:10064732, PubMed:11114332, PubMed:16230346, PubMed:7961706, PubMed:9281595). Mediates ATP-dependent transport of glutathione and glutathione conjugates, leukotriene C4, estradiol-17-beta-o-glucuronide, methotrexate, antiviral drugs and other xenobiotics (PubMed:10064732, PubMed:11114332, PubMed:16230346, PubMed:7961706, PubMed:9281595). Confers resistance to anticancer drugs by decreasing accumulation of drug in cells, and by mediating ATP- and GSH-dependent drug export (PubMed:9281595). Hydrolyzes ATP with low efficiency (PubMed:16230346). Catalyzes the export of sphingosine 1-phosphate from mast cells independently of their degranulation (PubMed:17050692). Participates in inflammatory response by allowing export of leukotriene C4 from leukotriene C4-synthezing cells (By similarity). Mediates ATP-dependent, GSH-independent cyclic GMP-AMP (cGAMP) export (PubMed:36070769). Thus, by limiting intracellular cGAMP concentrations negatively regulates the cGAS-STING pathway (PubMed:36070769)
- Specific Function
- Abc-type glutathione s-conjugate transporter activity
- Gene Name
- ABCC1
- Uniprot ID
- P33527
- Uniprot Name
- Multidrug resistance-associated protein 1
- Molecular Weight
- 171589.5 Da
References
- Grzywacz MJ, Yang JM, Hait WN: Effect of the multidrug resistance protein on the transport of the antiandrogen flutamide. Cancer Res. 2003 May 15;63(10):2492-8. [Article]
Drug created at June 13, 2005 13:24 / Updated at September 15, 2024 04:37