Nimesulide
Explore a selection of our essential drug information below, or:
Identification
- Summary
Nimesulide is a cyclooxygenase 2 inhibitor used to treat acute pain and primary dysmenorrhea.
- Generic Name
- Nimesulide
- DrugBank Accession Number
- DB04743
- Background
Nimesulide is a relatively COX-2 selective, non-steroidal anti-inflammatory drug (NSAID) with analgesic and antipyretic properties. Its approved indications are the treatment of acute pain, the symptomatic treatment of osteoarthritis and primary dysmenorrhoea in adolescents and adults above 12 years old. Due to concerns about the risk of hepatotoxicity, nimesulide has been withdrawn from market in many countries.
- Type
- Small Molecule
- Groups
- Approved, Investigational, Withdrawn
- Structure
- Weight
- Average: 308.31
Monoisotopic: 308.046692194 - Chemical Formula
- C13H12N2O5S
- Synonyms
- Nimesulida
- Nimesulide
- Nimesulidum
- External IDs
- R 805
- R-805
Pharmacology
- Indication
For the treatment of acute pain, the symptomatic treatment of osteoarthritis and primary dysmenorrhoea in adolescents and adults above 12 years old.
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 Menstrual cramps •••••••••••• Used in combination to treat Pain Combination Product in combination with: Lidocaine (DB00281) •••••••••••• ••••• Treatment of Pain •••••••••••• •••••••• ••• ••••••••• •••••••• ••• ••••••••••• ••••••• •••••• Treatment of Pain, acute •••••••••••• - Associated Therapies
- 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
Food, gender and advanced age have negligible effects on nimesulide pharmacokinetics.
- Mechanism of action
The therapeutic effects of Nimesulide are the result of its complete mode of action which targets a number of key mediators of the inflammatory process such as: COX-2 mediated prostaglandins, free radicals, proteolytic enzymes and histamine.
Target Actions Organism AProstaglandin G/H synthase 2 inhibitorHumans ATumor necrosis factor ligand superfamily member 10 modulatorHumans ALactotransferrin inhibitorHumans UGroup IIE secretory phospholipase A2 Not Available Humans - Absorption
Rapidly absorbed following oral administration.
- Volume of distribution
Not Available
- Protein binding
>97.5%
- Metabolism
Hepatic. Extensive biotransformation, mainly to 4-hydroxynimesulide (which also appears to be biologically active).
- Route of elimination
Renal (50%), fecal (29%)
- Half-life
1.8–4.7 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
Oral TDLO (human): 1.429 mg/kg; Oral TDLO (woman): 2 mg/kg; Oral LD50 (rat): 200 mg/kg; Oral LD50 (mouse): 392 mg/kg
- 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 Nimesulide may decrease the excretion rate of Abacavir which could result in a higher serum level. Abametapir The serum concentration of Nimesulide can be increased when it is combined with Abametapir. Abciximab The risk or severity of bleeding and hemorrhage can be increased when Nimesulide is combined with Abciximab. Abrocitinib The risk or severity of bleeding and thrombocytopenia can be increased when Nimesulide is combined with Abrocitinib. Acarbose The risk or severity of hypoglycemia can be increased when Nimesulide is combined with Acarbose. - Food Interactions
- Not Available
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.
- International/Other Brands
- Ainex / Aulin / Eskaflam / Mesulid / Nilsid / Nimalox / Nise / Sulide
- Mixture Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image DOLOFAST PLUS %1+%5 JEL, 30 GRAM Nimesulide (1 %) + Lidocaine (5 %) Gel Topical DİNÇSA İLAÇ SAN. VE TİC. A.Ş. 2019-09-24 Not applicable Turkey DOLOFAST PLUS %1+%5 JEL, 50 GRAM Nimesulide (1 %) + Lidocaine (5 %) Gel Topical DİNÇSA İLAÇ SAN. VE TİC. A.Ş. 2019-09-24 Not applicable Turkey EMULİD PLUS % 1 + % 5 JEL Nimesulide (1 %) + Lidocaine (5 %) Gel Topical VEM İLAÇ SAN. VE TİC. A.Ş. 2015-10-20 Not applicable Turkey ETNA COMBO %1 / %0.25 JEL Nimesulide (1 %) + Thiocolchicoside (0.25 %) Gel Topical GENVEON İLAÇ SAN. VE TİC. A.Ş. 2019-07-31 2021-10-04 Turkey ETNA COMBO 100 MG/8 MG TABLET, 14 ADET Nimesulide (100 mg) + Thiocolchicoside (8 mg) Tablet Oral GENVEON İLAÇ SAN. VE TİC. A.Ş. 2019-04-08 Not applicable Turkey
Categories
- ATC Codes
- M01AX17 — Nimesulide
- M01AX — Other antiinflammatory and antirheumatic agents, non-steroids
- M01A — ANTIINFLAMMATORY AND ANTIRHEUMATIC PRODUCTS, NON-STEROIDS
- M01 — ANTIINFLAMMATORY AND ANTIRHEUMATIC PRODUCTS
- M — MUSCULO-SKELETAL SYSTEM
- Drug Categories
- Agents causing hyperkalemia
- Agents that produce hypertension
- Amides
- Analgesics
- Analgesics, Non-Narcotic
- Anti-Inflammatory Agents
- Anti-Inflammatory Agents, Non-Steroidal
- Antiarrhythmic agents
- Antiinflammatory and Antirheumatic Products
- Antiinflammatory and Antirheumatic Products, Non-Steroids
- Antiinflammatory Preparations, Non-Steroids for Topical Use
- Antiplatelet agents
- Antirheumatic Agents
- Bradycardia-Causing Agents
- Calcium Channel Blockers
- Cyclooxygenase Inhibitors
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 Substrates
- Enzyme Inhibitors
- Musculo-Skeletal System
- Nephrotoxic agents
- Peripheral Nervous System Agents
- Selective Cyclooxygenase 2 Inhibitors (NSAIDs)
- Sensory System Agents
- Sulfones
- Sulfur Compounds
- Topical Products for Joint and Muscular Pain
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as diphenylethers. These are aromatic compounds containing two benzene rings linked to each other through an ether group.
- Kingdom
- Organic compounds
- Super Class
- Benzenoids
- Class
- Benzene and substituted derivatives
- Sub Class
- Diphenylethers
- Direct Parent
- Diphenylethers
- Alternative Parents
- Diarylethers / Sulfanilides / Nitrobenzenes / Nitroaromatic compounds / Phenoxy compounds / Phenol ethers / Organic sulfonamides / Organosulfonamides / Aminosulfonyl compounds / Organic oxoazanium compounds show 6 more
- Substituents
- Allyl-type 1,3-dipolar organic compound / Aminosulfonyl compound / Aromatic homomonocyclic compound / C-nitro compound / Diaryl ether / Diphenylether / Ether / Hydrocarbon derivative / Nitroaromatic compound / Nitrobenzene show 20 more
- Molecular Framework
- Aromatic homomonocyclic compounds
- External Descriptors
- C-nitro compound, aromatic ether, sulfonamide (CHEBI:44445)
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- V4TKW1454M
- CAS number
- 51803-78-2
- InChI Key
- HYWYRSMBCFDLJT-UHFFFAOYSA-N
- InChI
- InChI=1S/C13H12N2O5S/c1-21(18,19)14-12-8-7-10(15(16)17)9-13(12)20-11-5-3-2-4-6-11/h2-9,14H,1H3
- IUPAC Name
- N-(4-nitro-2-phenoxyphenyl)methanesulfonamide
- SMILES
- CS(=O)(=O)NC1=C(OC2=CC=CC=C2)C=C(C=C1)[N+]([O-])=O
References
- Synthesis Reference
Bernard Pirotte, Geraldine Piel, Philippe Neven, Isabelle Delneuville, Joszef Geczy, "Water-soluble nimesulide salt and its preparation, aqueous dolution containing it, nimesulide-based combinations and their uses." U.S. Patent US5756546, issued November, 1991.
US5756546- General References
- Not Available
- External Links
- KEGG Drug
- D01049
- PubChem Compound
- 4495
- PubChem Substance
- 46507721
- ChemSpider
- 4339
- BindingDB
- 50056999
- 53694
- ChEBI
- 44445
- ChEMBL
- CHEMBL56367
- ZINC
- ZINC000004617749
- Therapeutic Targets Database
- DPR000079
- PharmGKB
- PA137179528
- PDBe Ligand
- NIM
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Nimesulide
- PDB Entries
- 1zwp / 2oth / 3e9x / 3n8x / 4eix
- MSDS
- Download (23.5 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 Treatment Self Injurious Behaviour / Suicide 1 somestatus stop reason just information to hide Not Available Completed Not Available Acute Non-specific Low Back Pain 1 somestatus stop reason just information to hide Not Available Completed Treatment Temporomandibular Disorders (TMD) 1 somestatus stop reason just information to hide Not Available Completed Treatment Temporomandibular Joint Disorders 1 somestatus stop reason just information to hide 4 Completed Treatment Fibromyalgia 1 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Aerosol, foam Cutaneous 3 % Gel Cutaneous 3 % Mouthwash Oral Tablet, film coated Oral 100 mg Granule, for solution Oral 100 MG Gel Topical 3 % Tablet Oral 50 MG Tablet Oral 100 mg Mouthwash Oral 0.1 % Capsule Tablet, coated Oral Spray Topical Gel Topical Gel Topical 1 % Tablet Oral 200 MG Suspension Oral 1000 mg Granule, for suspension Oral Suppository Rectal Tablet Oral Suspension Oral 50 mg Gel 2 %w/w Gel Topical 3 g Gel Topical 2 g Powder, for solution Oral 100 mg Granule, for suspension Oral 400 MG Tablet Oral 400 MG Gel Topical Tablet Oral Suspension Oral 1 g Capsule, liquid filled Oral 100 mg Tablet, coated Oral 100 mg Granule, for solution Oral Granule Oral 100 MG Suppository Rectal 200 MG Granule, for suspension Oral 50 MG Tablet, effervescent Oral 100 MG Tablet, chewable Oral Capsule 100 MG Suspension Oral Tablet, orally disintegrating Tablet Oral 461.74 mg Granule Oral Powder Oral Granule, for suspension Oral 100 MG Powder, for suspension Oral 100 MG Tablet Oral 100.000 mg Powder Oral 100 mg/1sachet - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 143-144.5 °C PhysProp logP 2.60 SANGSTER (1993) - Predicted Properties
Property Value Source Water Solubility 0.0182 mg/mL ALOGPS logP 2.56 ALOGPS logP 1.79 Chemaxon logS -4.2 ALOGPS pKa (Strongest Acidic) 6.7 Chemaxon pKa (Strongest Basic) -3.7 Chemaxon Physiological Charge -1 Chemaxon Hydrogen Acceptor Count 4 Chemaxon Hydrogen Donor Count 1 Chemaxon Polar Surface Area 98.54 Å2 Chemaxon Rotatable Bond Count 4 Chemaxon Refractivity 75.3 m3·mol-1 Chemaxon Polarizability 28.93 Å3 Chemaxon Number of Rings 2 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 + 0.9952 Blood Brain Barrier + 0.6341 Caco-2 permeable - 0.55 P-glycoprotein substrate Non-substrate 0.8267 P-glycoprotein inhibitor I Non-inhibitor 0.5634 P-glycoprotein inhibitor II Non-inhibitor 0.8129 Renal organic cation transporter Non-inhibitor 0.8943 CYP450 2C9 substrate Non-substrate 0.6235 CYP450 2D6 substrate Non-substrate 0.8055 CYP450 3A4 substrate Substrate 0.5257 CYP450 1A2 substrate Inhibitor 0.9107 CYP450 2C9 inhibitor Inhibitor 0.8948 CYP450 2D6 inhibitor Non-inhibitor 0.9231 CYP450 2C19 inhibitor Non-inhibitor 0.7628 CYP450 3A4 inhibitor Non-inhibitor 0.8309 CYP450 inhibitory promiscuity High CYP Inhibitory Promiscuity 0.8952 Ames test AMES toxic 0.6488 Carcinogenicity Non-carcinogens 0.6116 Biodegradation Not ready biodegradable 0.9901 Rat acute toxicity 3.0832 LD50, mol/kg Not applicable hERG inhibition (predictor I) Strong inhibitor 0.5345 hERG inhibition (predictor II) Non-inhibitor 0.5574
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 169.710146 predictedDarkChem Lite v0.1.0 [M-H]- 184.698636 predictedDarkChem Lite v0.1.0 [M-H]- 155.17285 predictedDeepCCS 1.0 (2019) [M+H]+ 177.1196211 predictedDarkChem Lite v0.1.0 [M+H]+ 185.670236 predictedDarkChem Lite v0.1.0 [M+H]+ 157.53085 predictedDeepCCS 1.0 (2019) [M+Na]+ 183.1027333 predictedDarkChem Lite v0.1.0 [M+Na]+ 184.700436 predictedDarkChem Lite v0.1.0 [M+Na]+ 164.24092 predictedDeepCCS 1.0 (2019)
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Dual cyclooxygenase and peroxidase in the biosynthesis pathway of prostanoids, a class of C20 oxylipins mainly derived from arachidonate ((5Z,8Z,11Z,14Z)-eicosatetraenoate, AA, C20:4(n-6)), with a particular role in the inflammatory response (PubMed:11939906, PubMed:16373578, PubMed:19540099, PubMed:22942274, PubMed:26859324, PubMed:27226593, PubMed:7592599, PubMed:7947975, PubMed:9261177). The cyclooxygenase activity oxygenates AA to the hydroperoxy endoperoxide prostaglandin G2 (PGG2), and the peroxidase activity reduces PGG2 to the hydroxy endoperoxide prostaglandin H2 (PGH2), the precursor of all 2-series prostaglandins and thromboxanes (PubMed:16373578, PubMed:22942274, PubMed:26859324, PubMed:27226593, PubMed:7592599, PubMed:7947975, PubMed:9261177). This complex transformation is initiated by abstraction of hydrogen at carbon 13 (with S-stereochemistry), followed by insertion of molecular O2 to form the endoperoxide bridge between carbon 9 and 11 that defines prostaglandins. The insertion of a second molecule of O2 (bis-oxygenase activity) yields a hydroperoxy group in PGG2 that is then reduced to PGH2 by two electrons (PubMed:16373578, PubMed:22942274, PubMed:26859324, PubMed:27226593, PubMed:7592599, PubMed:7947975, PubMed:9261177). Similarly catalyzes successive cyclooxygenation and peroxidation of dihomo-gamma-linoleate (DGLA, C20:3(n-6)) and eicosapentaenoate (EPA, C20:5(n-3)) to corresponding PGH1 and PGH3, the precursors of 1- and 3-series prostaglandins (PubMed:11939906, PubMed:19540099). In an alternative pathway of prostanoid biosynthesis, converts 2-arachidonoyl lysophopholipids to prostanoid lysophopholipids, which are then hydrolyzed by intracellular phospholipases to release free prostanoids (PubMed:27642067). Metabolizes 2-arachidonoyl glycerol yielding the glyceryl ester of PGH2, a process that can contribute to pain response (PubMed:22942274). Generates lipid mediators from n-3 and n-6 polyunsaturated fatty acids (PUFAs) via a lipoxygenase-type mechanism. Oxygenates PUFAs to hydroperoxy compounds and then reduces them to corresponding alcohols (PubMed:11034610, PubMed:11192938, PubMed:9048568, PubMed:9261177). Plays a role in the generation of resolution phase interaction products (resolvins) during both sterile and infectious inflammation (PubMed:12391014). Metabolizes docosahexaenoate (DHA, C22:6(n-3)) to 17R-HDHA, a precursor of the D-series resolvins (RvDs) (PubMed:12391014). As a component of the biosynthetic pathway of E-series resolvins (RvEs), converts eicosapentaenoate (EPA, C20:5(n-3)) primarily to 18S-HEPE that is further metabolized by ALOX5 and LTA4H to generate 18S-RvE1 and 18S-RvE2 (PubMed:21206090). In vascular endothelial cells, converts docosapentaenoate (DPA, C22:5(n-3)) to 13R-HDPA, a precursor for 13-series resolvins (RvTs) shown to activate macrophage phagocytosis during bacterial infection (PubMed:26236990). In activated leukocytes, contributes to oxygenation of hydroxyeicosatetraenoates (HETE) to diHETES (5,15-diHETE and 5,11-diHETE) (PubMed:22068350, PubMed:26282205). Can also use linoleate (LA, (9Z,12Z)-octadecadienoate, C18:2(n-6)) as substrate and produce hydroxyoctadecadienoates (HODEs) in a regio- and stereospecific manner, being (9R)-HODE ((9R)-hydroxy-(10E,12Z)-octadecadienoate) and (13S)-HODE ((13S)-hydroxy-(9Z,11E)-octadecadienoate) its major products (By similarity). During neuroinflammation, plays a role in neuronal secretion of specialized preresolving mediators (SPMs) 15R-lipoxin A4 that regulates phagocytic microglia (By similarity)
- Specific Function
- enzyme binding
- Gene Name
- PTGS2
- Uniprot ID
- P35354
- Uniprot Name
- Prostaglandin G/H synthase 2
- Molecular Weight
- 68995.625 Da
References
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
- Rainsford KD: Nimesulide -- a multifactorial approach to inflammation and pain: scientific and clinical consensus. Curr Med Res Opin. 2006 Jun;22(6):1161-70. [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
- Yes
- Actions
- Modulator
- General Function
- Cytokine that binds to TNFRSF10A/TRAILR1, TNFRSF10B/TRAILR2, TNFRSF10C/TRAILR3, TNFRSF10D/TRAILR4 and possibly also to TNFRSF11B/OPG (PubMed:10549288, PubMed:26457518). Induces apoptosis. Its activity may be modulated by binding to the decoy receptors TNFRSF10C/TRAILR3, TNFRSF10D/TRAILR4 and TNFRSF11B/OPG that cannot induce apoptosis
- Specific Function
- cytokine activity
- Gene Name
- TNFSF10
- Uniprot ID
- P50591
- Uniprot Name
- Tumor necrosis factor ligand superfamily member 10
- Molecular Weight
- 32508.69 Da
References
- 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
- Yes
- Actions
- Inhibitor
- General Function
- Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate
- Specific Function
- cysteine-type endopeptidase inhibitor activity
- Gene Name
- LTF
- Uniprot ID
- P02788
- Uniprot Name
- Lactotransferrin
- Molecular Weight
- 78181.225 Da
References
- Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [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
- General Function
- Secretory calcium-dependent phospholipase A2 that primarily targets extracellular phospholipids (PubMed:10681567, PubMed:11922621, PubMed:28883454). Hydrolyzes the ester bond of the fatty acyl group attached at sn-2 position of phospholipids (phospholipase A2 activity), releasing various unsaturated fatty acids including oleoate, linoleoate, arachidonate, docosahexaenoate and lysophosphatidylethanolamines in preference to lysophosphatidylcholines (PubMed:10681567, PubMed:28883454). In response to high-fat diet, hydrolyzes minor lipoprotein phospholipids including phosphatidylserines, phosphatidylinositols and phosphatidylglycerols, altering lipoprotein composition and fat storage in adipose tissue and liver (By similarity). May act in an autocrine and paracrine manner (PubMed:11922621). Contributes to lipid remodeling of cellular membranes and generation of lipid mediators involved in pathogen clearance. Cleaves sn-2 fatty acyl chains of phosphatidylglycerols and phosphatidylethanolamines, which are major components of membrane phospholipids in bacteria (PubMed:11922621). Acts as a hair follicle phospholipase A2. Selectively releases lysophosphatidylethanolamines (LPE) and various unsaturated fatty acids in skin to regulate hair follicle homeostasis (By similarity). May regulate the inflammatory response by releasing arachidonate, a precursor of prostaglandins and leukotrienes (PubMed:11922621). Upon allergen exposure, may participate in allergic inflammatory response by enhancing leukotriene C4 synthesis and degranulation in mast cells (By similarity)
- Specific Function
- calcium ion binding
- Gene Name
- PLA2G2E
- Uniprot ID
- Q9NZK7
- Uniprot Name
- Group IIE secretory phospholipase A2
- Molecular Weight
- 15988.525 Da
References
- Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [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
- Uesawa Y, Takeuchi T, Mohri K: Integrated analysis on the physicochemical properties of dihydropyridine calcium channel blockers in grapefruit juice interactions. Curr Pharm Biotechnol. 2012 Jul;13(9):1705-17. [Article]
Drug created at September 11, 2007 17:49 / Updated at August 26, 2024 19:21