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Identification
- Summary
Aminophenazone is an analgesic drug used to treat acute migraine attacks in combination with ergotamine and caffeine.
- Generic Name
- Aminophenazone
- DrugBank Accession Number
- DB01424
- Background
Aminophenazone is a pyrazolone with analgesic, anti-inflammatory, and antipyretic properties that carries a risk of agranulocytosis. In biomedical applications, radiolabelled (13C-labeled) aminophenazone has been used in breath tests to measure the cytochrome P-450 metabolic activity in liver function tests. The FDA suspended the use of aminophenazone due to its association with agranulocytosis, a life-threatening side effect.2,3
- Type
- Small Molecule
- Groups
- Approved, Withdrawn
- Structure
Structure for Aminophenazone (DB01424)
- Weight
- Average: 231.2936
Monoisotopic: 231.137162181 - Chemical Formula
- C13H17N3O
- Synonyms
- (Dimethylamino)phenazone
- 1-Phenyl-2,3-dimethyl-4-(dimethylamino)-5-pyrazolone
- 1-Phenyl-2,3-dimethyl-4-dimethylaminopyrazol-5-one
- 1,5-Dimethyl-4-dimethylamino-2-phenyl-3-pyrazolone
- 2,3-Dimethyl-4-dimethylamino-1-phenyl-5-pyrazolone
- 3-Keto-1,5-dimethyl-4-dimethylamino-2-phenyl-2,3-dihydropyrazole
- 4-(Dimethylamino)-1,2-dihydro-1,5-dimethyl-2-phenyl-3H-pyrazol-3-one
- 4-(Dimethylamino)-1,5-dimethyl-2-phenyl-1,2-dihydro-3H-pyrazol-3-one
- 4-(Dimethylamino)antipyrine
- 4-Dimethylamino-1-phenyl-2,3-dimethylpyrazolone
- 4-Dimethylamino-2,3-dimethyl-1-phenyl-3-pyrazolin-5-one
- 4-Dimethylamino-2,3-dimethyl-1-phenyl-5-pyrazolone
- 4-Dimethylaminoantipyrine
- 4-Dimethylaminophenazone
- Aminofenazona
- Aminofenazone
- Aminophenazon
- Aminophenazone
- Aminophenazonum
- Aminopyrine
- Dimethylaminoantipyrine
- Dimethylaminoazophene
- Dimethylaminophenazon
- Dimethylaminophenazone
- Dimethylaminophenyldimethylpyrazolone
- Dipyrine
- External IDs
- NSC-4993
Pharmacology
- Indication
Formerly widely used as an antipyretic and analgesic in rheumatism, neuritis, and common colds. Currently used to measure total body water.
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Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Used in combination for symptomatic treatment of Acute migraine Combination Product in combination with: Caffeine (DB00201), Ergotamine (DB00696) •••••••••••• ••••••••••• - 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
Aminophenazone exhibits analgesic, anti-inflammatory, and antipyretic properties.
- Mechanism of action
Aminophenazone is metabolized very slowly by normal newborn babies. In older infants, a higher amount of exhaled 13-CO2 is observed.
- Absorption
Not Available
- Volume of distribution
Not Available
- Protein binding
Not Available
- Metabolism
Hover over products below to view reaction partners
- Route of elimination
Not Available
- Half-life
Not Available
- 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
Can cause life-threatening agranulocytosis.
- 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 Aminophenazone may decrease the excretion rate of Abacavir which could result in a higher serum level. Abametapir The serum concentration of Aminophenazone can be increased when it is combined with Abametapir. Abatacept The metabolism of Aminophenazone can be increased when combined with Abatacept. Abciximab The risk or severity of bleeding and hemorrhage can be increased when Aminophenazone is combined with Abciximab. Abiraterone The serum concentration of Aminophenazone can be increased when it is combined with Abiraterone. - 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.- Mixture Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image VIRDEX Aminophenazone (250 MG) + Caffeine (100 MG) + Ergotamine tartrate (0.5 MG) Suppository Rectal Fulton Medicinali S.P.A. 2014-07-08 Not applicable Italy 
VIRDEX Aminophenazone (250 MG) + Caffeine (100 MG) + Ergotamine tartrate (2 MG) Suppository Rectal Fulton Medicinali S.P.A. 2014-07-08 Not applicable Italy
Categories
- ATC Codes
- N02BB53 — Aminophenazone, combinations excl. psycholepticsN02BB03 — AminophenazoneN02BB73 — Aminophenazone, combinations with psycholeptics
- Drug Categories
- Agents causing hyperkalemia
- Agents that produce hypertension
- Analgesics
- Anti-Inflammatory Agents
- Anti-Inflammatory Agents, Non-Steroidal
- Cytochrome P-450 CYP1A2 Substrates
- Cytochrome P-450 CYP2C18 Substrates
- Cytochrome P-450 CYP2C19 Inhibitors
- Cytochrome P-450 CYP2C19 Substrates
- Cytochrome P-450 CYP2C8 Substrates
- Cytochrome P-450 CYP2C9 Substrates
- Cytochrome P-450 CYP2D6 Substrates
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 Enzyme Inhibitors
- Cytochrome P-450 Substrates
- Nephrotoxic agents
- Nervous System
- Non COX-2 selective NSAIDS
- OAT1/SLC22A6 inhibitors
- Pyrazoles
- Pyrazolones
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as phenylpyrazoles. These are compounds containing a phenylpyrazole skeleton, which consists of a pyrazole bound to a phenyl group.
- Kingdom
- Organic compounds
- Super Class
- Organoheterocyclic compounds
- Class
- Azoles
- Sub Class
- Pyrazoles
- Direct Parent
- Phenylpyrazoles
- Alternative Parents
- Dialkylarylamines / Pyrazolones / Benzene and substituted derivatives / Vinylogous amides / Heteroaromatic compounds / Lactams / Azacyclic compounds / Organopnictogen compounds / Organooxygen compounds / Organic oxides show 1 more
- Substituents
- Amine / Aromatic heteromonocyclic compound / Azacycle / Benzenoid / Dialkylarylamine / Heteroaromatic compound / Hydrocarbon derivative / Lactam / Monocyclic benzene moiety / Organic nitrogen compound show 10 more
- Molecular Framework
- Aromatic heteromonocyclic compounds
- External Descriptors
- tertiary amino compound, pyrazolone (CHEBI:160246)
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- 01704YP3MO
- CAS number
- 58-15-1
- InChI Key
- RMMXTBMQSGEXHJ-UHFFFAOYSA-N
- InChI
- InChI=1S/C13H17N3O/c1-10-12(14(2)3)13(17)16(15(10)4)11-8-6-5-7-9-11/h5-9H,1-4H3
- IUPAC Name
- 4-(dimethylamino)-1,5-dimethyl-2-phenyl-2,3-dihydro-1H-pyrazol-3-one
- SMILES
- CN(C)C1=C(C)N(C)N(C1=O)C1=CC=CC=C1
References
- General References
- Rating D, Langhans CD: Breath tests: concepts, applications and limitations. Eur J Pediatr. 1997 Aug;156 Suppl 1:S18-23. [Article]
- Chan TY, Chan AW: Aminopyrine-induced blood dyscrasias--still a problem in many parts of the world. Pharmacoepidemiol Drug Saf. 1996 Jul;5(4):215-9. doi: 10.1002/(SICI)1099-1557(199607)5:4<215::AID-PDS208>3.0.CO;2-5. [Article]
- Code of Federal Regulations 216.24: Drug products withdrawn or removed from the market for reasons of safety or effectiveness. [Link]
- External Links
- Human Metabolome Database
- HMDB0015493
- KEGG Drug
- D00556
- KEGG Compound
- C07539
- PubChem Compound
- 6009
- PubChem Substance
- 46504975
- ChemSpider
- 5787
- BindingDB
- 74258
- 695
- ChEBI
- 160246
- ChEMBL
- CHEMBL288470
- ZINC
- ZINC000000057115
- PharmGKB
- PA164748135
- Wikipedia
- Aminophenazone
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 data
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Tablet, film coated Oral 200 MG Solution Oral Suppository Rectal - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 134.5 °C PhysProp water solubility 5.44E+004 mg/L (at 30 °C) YALKOWSKY,SH & DANNENFELSER,RM (1992) logP 1.00 HANSCH,C ET AL. (1995) logS -0.63 ADME Research, USCD Caco2 permeability -4.44 ADME Research, USCD pKa 5 SANGSTER (1994) - Predicted Properties
Property Value Source Water Solubility 22.5 mg/mL ALOGPS logP 0.94 ALOGPS logP 1.15 Chemaxon logS -1 ALOGPS pKa (Strongest Basic) 3.66 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 3 Chemaxon Hydrogen Donor Count 0 Chemaxon Polar Surface Area 26.79 Å2 Chemaxon Rotatable Bond Count 2 Chemaxon Refractivity 70.11 m3·mol-1 Chemaxon Polarizability 25.86 Å3 Chemaxon Number of Rings 2 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 + 0.9845 Caco-2 permeable + 0.8867 P-glycoprotein substrate Non-substrate 0.7772 P-glycoprotein inhibitor I Non-inhibitor 0.7283 P-glycoprotein inhibitor II Non-inhibitor 0.8382 Renal organic cation transporter Non-inhibitor 0.8779 CYP450 2C9 substrate Non-substrate 0.7595 CYP450 2D6 substrate Substrate 0.8154 CYP450 3A4 substrate Substrate 0.7049 CYP450 1A2 substrate Inhibitor 0.9107 CYP450 2C9 inhibitor Non-inhibitor 0.9337 CYP450 2D6 inhibitor Non-inhibitor 0.9231 CYP450 2C19 inhibitor Non-inhibitor 0.957 CYP450 3A4 inhibitor Non-inhibitor 0.8309 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.6183 Ames test AMES toxic 0.6234 Carcinogenicity Non-carcinogens 0.835 Biodegradation Not ready biodegradable 0.9871 Rat acute toxicity 2.8773 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9691 hERG inhibition (predictor II) Non-inhibitor 0.7392
Spectra
- Mass Spec (NIST)
- Download (8.35 KB)
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 161.911232 predictedDarkChem Lite v0.1.0 [M-H]- 154.737173 predictedDarkChem Lite v0.1.0 [M-H]- 162.291932 predictedDarkChem Lite v0.1.0 [M-H]- 158.22194 predictedDeepCCS 1.0 (2019) [M+H]+ 163.105332 predictedDarkChem Lite v0.1.0 [M+H]+ 158.8144779 predictedDarkChem Lite v0.1.0 [M+H]+ 163.035732 predictedDarkChem Lite v0.1.0 [M+H]+ 160.57994 predictedDeepCCS 1.0 (2019) [M+Na]+ 162.397032 predictedDarkChem Lite v0.1.0 [M+Na]+ 165.2300379 predictedDarkChem Lite v0.1.0 [M+Na]+ 166.6731 predictedDeepCCS 1.0 (2019)
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 and steroids (PubMed:12865317, PubMed:15766564, PubMed:19965576, PubMed:21576599, PubMed:7574697, PubMed:9435160, PubMed:9866708). 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:12865317, PubMed:15766564, PubMed:19965576, PubMed:21576599, PubMed:7574697, PubMed:9435160, PubMed:9866708). Catalyzes the epoxidation of double bonds of polyunsaturated fatty acids (PUFA) (PubMed:15766564, PubMed:19965576, PubMed:7574697, PubMed:9866708). Catalyzes the hydroxylation of carbon-hydrogen bonds. Metabolizes cholesterol toward 25-hydroxycholesterol, a physiological regulator of cellular cholesterol homeostasis (PubMed:21576599). Exhibits low catalytic activity for the formation of catechol estrogens from 17beta-estradiol (E2) and estrone (E1), namely 2-hydroxy E1 and E2 (PubMed:12865317). Catalyzes bisallylic hydroxylation and hydroxylation with double-bond migration of polyunsaturated fatty acids (PUFA) (PubMed:9435160, PubMed:9866708). Also metabolizes plant monoterpenes such as limonene. Oxygenates (R)- and (S)-limonene to produce carveol and perillyl alcohol (PubMed:11950794). Contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S-warfarin, diclofenac, phenytoin, tolbutamide and losartan (PubMed:25994031)
- Specific Function
- (r)-limonene 6-monooxygenase activity
- Gene Name
- CYP2C9
- Uniprot ID
- P11712
- Uniprot Name
- Cytochrome P450 2C9
- Molecular Weight
- 55627.365 Da
References
- Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [Article]
- Rendic S: Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448. [Article]
- Niwa T, Sato R, Yabusaki Y, Ishibashi F, Katagiri M: Contribution of human hepatic cytochrome P450s and steroidogenic CYP17 to the N-demethylation of aminopyrine. Xenobiotica. 1999 Feb;29(2):187-93. doi: 10.1080/004982599238731 . [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of fatty acids, steroids and retinoids (PubMed:18698000, PubMed:19965576, PubMed:20972997, PubMed:21289075, 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) (PubMed:18698000, PubMed:19965576, PubMed:20972997, PubMed:21289075, PubMed:21576599). Catalyzes the epoxidation of double bonds of polyunsaturated fatty acids (PUFA) (PubMed:19965576, PubMed:20972997). Metabolizes endocannabinoid arachidonoylethanolamide (anandamide) to 20-hydroxyeicosatetraenoic acid ethanolamide (20-HETE-EA) and 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed:18698000, PubMed:21289075). Catalyzes the hydroxylation of carbon-hydrogen bonds. Metabolizes cholesterol toward 25-hydroxycholesterol, a physiological regulator of cellular cholesterol homeostasis (PubMed:21576599). Catalyzes the oxidative transformations of all-trans retinol to all-trans retinal, a precursor for the active form all-trans-retinoic acid (PubMed:10681376). Also involved in the oxidative metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants
- Specific Function
- Anandamide 11,12 epoxidase activity
- Gene Name
- CYP2D6
- Uniprot ID
- P10635
- Uniprot Name
- Cytochrome P450 2D6
- Molecular Weight
- 55768.94 Da
References
- Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [Article]
- Niwa T, Sato R, Yabusaki Y, Ishibashi F, Katagiri M: Contribution of human hepatic cytochrome P450s and steroidogenic CYP17 to the N-demethylation of aminopyrine. Xenobiotica. 1999 Feb;29(2):187-93. doi: 10.1080/004982599238731 . [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
- Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [Article]
- Niwa T, Sato R, Yabusaki Y, Ishibashi F, Katagiri M: Contribution of human hepatic cytochrome P450s and steroidogenic CYP17 to the N-demethylation of aminopyrine. Xenobiotica. 1999 Feb;29(2):187-93. doi: 10.1080/004982599238731 . [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- A cytochrome P450 monooxygenase involved in retinoid metabolism. Hydroxylates all trans-retinoic acid (atRA) to 4-hydroxyretinoate and may modulate atRA signaling and clearance. 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 (CPR; NADPH-ferrihemoprotein reductase)
- Specific Function
- Arachidonic acid epoxygenase activity
- Gene Name
- CYP2C18
- Uniprot ID
- P33260
- Uniprot Name
- Cytochrome P450 2C18
- Molecular Weight
- 55710.075 Da
References
- Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [Article]
- Niwa T, Sato R, Yabusaki Y, Ishibashi F, Katagiri M: Contribution of human hepatic cytochrome P450s and steroidogenic CYP17 to the N-demethylation of aminopyrine. Xenobiotica. 1999 Feb;29(2):187-93. doi: 10.1080/004982599238731 . [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- A cytochrome P450 monooxygenase involved in corticoid and androgen biosynthesis (PubMed:22266943, PubMed:25301938, PubMed:27339894, PubMed:9452426). Catalyzes 17-alpha hydroxylation of C21 steroids, which is common for both pathways. A second oxidative step, required only for androgen synthesis, involves an acyl-carbon cleavage. The 17-alpha hydroxy intermediates, as part of adrenal glucocorticoids biosynthesis pathway, are precursors of cortisol (Probable) (PubMed:25301938, PubMed:9452426). Hydroxylates steroid hormones, pregnenolone and progesterone to form 17-alpha hydroxy metabolites, followed by the cleavage of the C17-C20 bond to form C19 steroids, dehydroepiandrosterone (DHEA) and androstenedione (PubMed:22266943, PubMed:25301938, PubMed:27339894, PubMed:36640554, PubMed:9452426). Has 16-alpha hydroxylase activity. Catalyzes 16-alpha hydroxylation of 17-alpha hydroxy pregnenolone, followed by the cleavage of the C17-C20 bond to form 16-alpha-hydroxy DHEA (PubMed:36640554). Also 16-alpha hydroxylates androgens, relevant for estriol synthesis (PubMed:25301938, PubMed:27339894). 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 (CPR; NADPH-ferrihemoprotein reductase) (PubMed:22266943, PubMed:25301938, PubMed:27339894, PubMed:9452426)
- Specific Function
- 17-alpha-hydroxyprogesterone aldolase activity
- Gene Name
- CYP17A1
- Uniprot ID
- P05093
- Uniprot Name
- Steroid 17-alpha-hydroxylase/17,20 lyase
- Molecular Weight
- 57369.995 Da
References
- Niwa T, Sato R, Yabusaki Y, Ishibashi F, Katagiri M: Contribution of human hepatic cytochrome P450s and steroidogenic CYP17 to the N-demethylation of aminopyrine. Xenobiotica. 1999 Feb;29(2):187-93. doi: 10.1080/004982599238731 . [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of polyunsaturated fatty acids (PUFA) (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:18577768, PubMed:19965576, PubMed:20972997). Catalyzes the hydroxylation of carbon-hydrogen bonds. Hydroxylates PUFA specifically at the omega-1 position (PubMed:18577768). Catalyzes the epoxidation of double bonds of PUFA (PubMed:19965576, PubMed:20972997). Also metabolizes plant monoterpenes such as limonene. Oxygenates (R)- and (S)-limonene to produce carveol and perillyl alcohol (PubMed:11950794). Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and imipramine. Hydroxylates fenbendazole at the 4' position (PubMed:23959307)
- Specific Function
- (r)-limonene 6-monooxygenase activity
- Gene Name
- CYP2C19
- Uniprot ID
- P33261
- Uniprot Name
- Cytochrome P450 2C19
- Molecular Weight
- 55944.565 Da
References
- Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [Article]
- Niwa T, Tsutsui M, Kishimoto K, Yabusaki Y, Ishibashi F, Katagiri M: Inhibition of drug-metabolizing enzyme activity in human hepatic cytochrome P450s by bisphenol A. Biol Pharm Bull. 2000 Apr;23(4):498-501. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- Curator comments
- Data for this enzyme action is limited to an in vitro study.
- 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
- Niwa T, Sato R, Yabusaki Y, Ishibashi F, Katagiri M: Contribution of human hepatic cytochrome P450s and steroidogenic CYP17 to the N-demethylation of aminopyrine. Xenobiotica. 1999 Feb;29(2):187-93. doi: 10.1080/004982599238731 . [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:11093772, PubMed:14559847, PubMed:15766564, PubMed:19965576, PubMed:7574697). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:11093772, PubMed:14559847, PubMed:15766564, PubMed:19965576, PubMed:7574697). Primarily catalyzes the epoxidation of double bonds of polyunsaturated fatty acids (PUFA) with a preference for the last double bond (PubMed:15766564, PubMed:19965576, PubMed:7574697). Catalyzes the hydroxylation of carbon-hydrogen bonds. Metabolizes all trans-retinoic acid toward its 4-hydroxylated form (PubMed:11093772). Displays 16-alpha hydroxylase activity toward estrogen steroid hormones, 17beta-estradiol (E2) and estrone (E1) (PubMed:14559847). Plays a role in the oxidative metabolism of xenobiotics. It is the principal enzyme responsible for the metabolism of the anti-cancer drug paclitaxel (taxol) (PubMed:26427316)
- Specific Function
- Arachidonic acid epoxygenase activity
- Gene Name
- CYP2C8
- Uniprot ID
- P10632
- Uniprot Name
- Cytochrome P450 2C8
- Molecular Weight
- 55824.275 Da
References
- Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [Article]
- Niwa T, Sato R, Yabusaki Y, Ishibashi F, Katagiri M: Contribution of human hepatic cytochrome P450s and steroidogenic CYP17 to the N-demethylation of aminopyrine. Xenobiotica. 1999 Feb;29(2):187-93. doi: 10.1080/004982599238731 . [Article]
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Secondary active transporter that functions as a Na(+)-independent organic anion (OA)/dicarboxylate antiporter where the uptake of one molecule of OA into the cell is coupled with an efflux of one molecule of intracellular dicarboxylate such as 2-oxoglutarate or glutarate (PubMed:11669456, PubMed:11907186, PubMed:14675047, PubMed:22108572, PubMed:23832370, PubMed:28534121, PubMed:9950961). Mediates the uptake of OA across the basolateral side of proximal tubule epithelial cells, thereby contributing to the renal elimination of endogenous OA from the systemic circulation into the urine (PubMed:9887087). Functions as a biopterin transporters involved in the uptake and the secretion of coenzymes tetrahydrobiopterin (BH4), dihydrobiopterin (BH2) and sepiapterin to urine, thereby determining baseline levels of blood biopterins (PubMed:28534121). Transports prostaglandin E2 (PGE2) and prostaglandin F2-alpha (PGF2-alpha) and may contribute to their renal excretion (PubMed:11907186). Also mediates the uptake of cyclic nucleotides such as cAMP and cGMP (PubMed:26377792). Involved in the transport of neuroactive tryptophan metabolites kynurenate (KYNA) and xanthurenate (XA) and may contribute to their secretion from the brain (PubMed:22108572, PubMed:23832370). May transport glutamate (PubMed:26377792). Also involved in the disposition of uremic toxins and potentially toxic xenobiotics by the renal organic anion secretory pathway, helping reduce their undesired toxicological effects on the body (PubMed:11669456, PubMed:14675047). Uremic toxins include the indoxyl sulfate (IS), hippurate/N-benzoylglycine (HA), indole acetate (IA), 3-carboxy-4- methyl-5-propyl-2-furanpropionate (CMPF) and urate (PubMed:14675047, PubMed:26377792). Xenobiotics include the mycotoxin ochratoxin (OTA) (PubMed:11669456). May also contribute to the transport of organic compounds in testes across the blood-testis-barrier (PubMed:35307651)
- Specific Function
- Alpha-ketoglutarate transmembrane transporter activity
- Gene Name
- SLC22A6
- Uniprot ID
- Q4U2R8
- Uniprot Name
- Solute carrier family 22 member 6
- Molecular Weight
- 61815.78 Da
References
- Apiwattanakul N, Sekine T, Chairoungdua A, Kanai Y, Nakajima N, Sophasan S, Endou H: Transport properties of nonsteroidal anti-inflammatory drugs by organic anion transporter 1 expressed in Xenopus laevis oocytes. Mol Pharmacol. 1999 May;55(5):847-54. [Article]
Drug created at July 24, 2007 11:44 / Updated at November 11, 2022 16:49