Identification

Name
Suprofen
Accession Number
DB00870  (APRD00230)
Type
Small Molecule
Groups
Approved, Withdrawn
Description

An ibuprofen-type anti-inflammatory analgesic and antipyretic. It inhibits prostaglandin synthesis and has been proposed as an anti-arthritic. It is no longer approved for use in the United States.

Structure
Thumb
Synonyms
  • (+-)-2-(P-(2-Thenoyl)phenyl)propionic acid
  • 2-(4-(2-Thenoyl)phenyl)propionsaeure
  • 2-[4-(Thiophene-2-carbonyl)-phenyl]-propionic acid
  • 4-(2-Thenoyl)hydratropsaeure
  • alpha-Methyl-4-(2-thienylcarbonyl)benzeneacetic acid
  • P-2-Thenoylhydratropic acid
  • Suprofen
  • Suprofène
  • Suprofene
  • Suprofeno
  • Suprofenum
  • SUTOPROFEN
External IDs
R 25061 / TN 762
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
ProfenalSolution10 mg/1OphthalmicALCON LABORATORIES, INC.2006-02-23Not applicableUs
International/Other Brands
Profenal (Janssen Pharmaceuticals) / Srendam (Pola Pharma) / Sulprotin (Taiyo Pharmaceutical) / Topalgic (Alfresa Pharma)
Categories
UNII
988GU2F9PE
CAS number
40828-46-4
Weight
Average: 260.308
Monoisotopic: 260.05071494
Chemical Formula
C14H12O3S
InChI Key
MDKGKXOCJGEUJW-UHFFFAOYSA-N
InChI
InChI=1S/C14H12O3S/c1-9(14(16)17)10-4-6-11(7-5-10)13(15)12-3-2-8-18-12/h2-9H,1H3,(H,16,17)
IUPAC Name
2-[4-(thiophene-2-carbonyl)phenyl]propanoic acid
SMILES
CC(C(O)=O)C1=CC=C(C=C1)C(=O)C1=CC=CS1

Pharmacology

Indication

Used as eye drops to inhibit the miosis (pupil constriction) that may occur during ocular surgery.

Pharmacodynamics

Suprofen is a non-steroidal anti-inflammatory analgesic and antipyretic. Ophthalmic anti-inflammatory medicines are used in the eye to lessen problems that can occur during or after some kinds of eye surgery. Sometimes, the pupil of the eye gets smaller during an operation (pupil constriction), making it more difficult for the surgeon to reach some areas of the eye. Suprofen is used to help prevent this.

Mechanism of action

Suprofen binds to the cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) isoenzymes, preventing the synthesis of prostaglandins and reducing the inflammatory response. Cyclooxygenase catalyses the formation of prostaglandins and thromboxane from arachidonic acid (itself derived from the cellular phospholipid bilayer by phospholipase A2). Prostaglandins act (among other things) as messenger molecules in the process of inflammation. The overall result is a reduction in pain and inflammation in the eyes and the prevention of pupil constriction during surgery. Normally trauma to the anterior segment of the eye (especially the iris) increases endogenous prostaglandin synthesis which leads to constriction of the iris sphincter.

TargetActionsOrganism
AProstaglandin G/H synthase 1
inhibitor
Human
AProstaglandin G/H synthase 2
inhibitor
Human
Absorption
Not Available
Volume of distribution
Not Available
Protein binding

20%

Metabolism

Primarily hepatic (mainly via cytochrome P450 isozyme 2C9).

Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity

Symptoms of overdose include bleeding in the eye or redness or swelling of the eye or the eyelid, blurred vision or other change in vision, fever or chills, itching or tearing, nausea or vomiting, pain, sensitivity to light, shortness of breath, sticky or matted eyelashes, swelling of face, throbbing pain, tightness in chest, troubled breathing, and wheezing.

Affected organisms
  • Humans and other mammals
Pathways
PathwayCategory
Suprofen Action PathwayDrug action
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
AceclofenacThe risk or severity of adverse effects can be increased when Suprofen is combined with Aceclofenac.
AcemetacinThe risk or severity of adverse effects can be increased when Suprofen is combined with Acemetacin.
Acetylsalicylic acidThe risk or severity of adverse effects can be increased when Suprofen is combined with Acetylsalicylic acid.
AlclofenacThe risk or severity of adverse effects can be increased when Suprofen is combined with Alclofenac.
AlminoprofenThe risk or severity of adverse effects can be increased when Suprofen is combined with Alminoprofen.
AloxiprinThe therapeutic efficacy of Aloxiprin can be decreased when used in combination with Suprofen.
AminophenazoneThe risk or severity of adverse effects can be increased when Suprofen is combined with Aminophenazone.
Aminosalicylic AcidThe therapeutic efficacy of Aminosalicylic Acid can be decreased when used in combination with Suprofen.
AntipyrineThe risk or severity of adverse effects can be increased when Suprofen is combined with Antipyrine.
AntrafenineThe risk or severity of adverse effects can be increased when Suprofen is combined with Antrafenine.
Food Interactions
Not Available

References

General References
Not Available
External Links
Human Metabolome Database
HMDB0015008
KEGG Drug
D00452
KEGG Compound
C07320
PubChem Compound
5359
PubChem Substance
46508210
ChemSpider
5166
BindingDB
50090676
ChEBI
9362
ChEMBL
CHEMBL956
Therapeutic Targets Database
DAP000730
PharmGKB
PA451569
Drugs.com
Drugs.com Drug Page
Wikipedia
Suprofen
ATC Codes
M01AE07 — Suprofen
MSDS
Download (50.8 KB)

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
  • Alcon laboratories inc
Packagers
Not Available
Dosage forms
FormRouteStrength
SolutionOphthalmic10 mg/1
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)124.3 °CPhysProp
water solubilitylimited solubilityNot Available
logP2.2Not Available
pKa3.91MERCK INDEX (1996)
Predicted Properties
PropertyValueSource
Water Solubility0.0422 mg/mLALOGPS
logP3.16ALOGPS
logP3.53ChemAxon
logS-3.8ALOGPS
pKa (Strongest Acidic)4.01ChemAxon
pKa (Strongest Basic)-7.8ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area54.37 Å2ChemAxon
Rotatable Bond Count4ChemAxon
Refractivity69.41 m3·mol-1ChemAxon
Polarizability26.84 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9927
Blood Brain Barrier+0.9289
Caco-2 permeable+0.6039
P-glycoprotein substrateNon-substrate0.7298
P-glycoprotein inhibitor INon-inhibitor0.9534
P-glycoprotein inhibitor IINon-inhibitor0.9664
Renal organic cation transporterNon-inhibitor0.8998
CYP450 2C9 substrateNon-substrate0.6293
CYP450 2D6 substrateNon-substrate0.9226
CYP450 3A4 substrateNon-substrate0.8098
CYP450 1A2 substrateNon-inhibitor0.9046
CYP450 2C9 inhibitorNon-inhibitor0.8607
CYP450 2D6 inhibitorNon-inhibitor0.9231
CYP450 2C19 inhibitorNon-inhibitor0.8958
CYP450 3A4 inhibitorNon-inhibitor0.9526
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8682
Ames testNon AMES toxic0.9398
CarcinogenicityNon-carcinogens0.7568
BiodegradationReady biodegradable0.7714
Rat acute toxicity3.1892 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9869
hERG inhibition (predictor II)Non-inhibitor0.9716
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSNot Available
MS/MS Spectrum - , positiveLC-MS/MSsplash10-03di-2790000000-0cf8f983c8b216c951b3

Taxonomy

Description
This compound belongs to the class of organic compounds known as aryl-phenylketones. These are aromatic compounds containing a ketone substituted by one aryl group, and a phenyl group.
Kingdom
Organic compounds
Super Class
Organic oxygen compounds
Class
Organooxygen compounds
Sub Class
Carbonyl compounds
Direct Parent
Aryl-phenylketones
Alternative Parents
Phenylpropanoic acids / Monocyclic monoterpenoids / Aromatic monoterpenoids / Thiophene carboxylic acids and derivatives / Benzoyl derivatives / Heteroaromatic compounds / Monocarboxylic acids and derivatives / Carboxylic acids / Organic oxides / Hydrocarbon derivatives
Substituents
Aryl-phenylketone / 2-phenylpropanoic-acid / P-cymene / Aromatic monoterpenoid / Monocyclic monoterpenoid / Monoterpenoid / Benzoyl / Thiophene carboxylic acid or derivatives / Benzenoid / Monocyclic benzene moiety
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
monocarboxylic acid, thiophenes, aromatic ketone (CHEBI:9362)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Prostaglandin-endoperoxide synthase activity
Specific Function
Converts arachidonate to prostaglandin H2 (PGH2), a committed step in prostanoid synthesis. Involved in the constitutive production of prostanoids in particular in the stomach and platelets. In gas...
Gene Name
PTGS1
Uniprot ID
P23219
Uniprot Name
Prostaglandin G/H synthase 1
Molecular Weight
68685.82 Da
References
  1. Loll PJ, Picot D, Ekabo O, Garavito RM: Synthesis and use of iodinated nonsteroidal antiinflammatory drug analogs as crystallographic probes of the prostaglandin H2 synthase cyclooxygenase active site. Biochemistry. 1996 Jun 11;35(23):7330-40. [PubMed:8652509]
  2. Bender A, Scheiber J, Glick M, Davies JW, Azzaoui K, Hamon J, Urban L, Whitebread S, Jenkins JL: Analysis of pharmacology data and the prediction of adverse drug reactions and off-target effects from chemical structure. ChemMedChem. 2007 Jun;2(6):861-73. [PubMed:17477341]
  3. Llorens O, Perez JJ, Palomer A, Mauleon D: Differential binding mode of diverse cyclooxygenase inhibitors. J Mol Graph Model. 2002 Mar;20(5):359-71. [PubMed:11885959]
  4. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Prostaglandin-endoperoxide synthase activity
Specific Function
Converts arachidonate to prostaglandin H2 (PGH2), a committed step in prostanoid synthesis. Constitutively expressed in some tissues in physiological conditions, such as the endothelium, kidney and...
Gene Name
PTGS2
Uniprot ID
P35354
Uniprot Name
Prostaglandin G/H synthase 2
Molecular Weight
68995.625 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
  3. Llorens O, Perez JJ, Palomer A, Mauleon D: Differential binding mode of diverse cyclooxygenase inhibitors. J Mol Graph Model. 2002 Mar;20(5):359-71. [PubMed:11885959]

Enzymes

Details
1. Cytochrome P450 2C9
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
Curator comments
This enzyme effect is supported only by data from in vitro studies.
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C9
Uniprot ID
P11712
Uniprot Name
Cytochrome P450 2C9
Molecular Weight
55627.365 Da
References
  1. Hutzler JM, Balogh LM, Zientek M, Kumar V, Tracy TS: Mechanism-based inactivation of cytochrome P450 2C9 by tienilic acid and (+/-)-suprofen: a comparison of kinetics and probe substrate selection. Drug Metab Dispos. 2009 Jan;37(1):59-65. doi: 10.1124/dmd.108.023358. Epub 2008 Oct 6. [PubMed:18838506]
  2. O'Donnell JP, Dalvie DK, Kalgutkar AS, Obach RS: Mechanism-based inactivation of human recombinant P450 2C9 by the nonsteroidal anti-inflammatory drug suprofen. Drug Metab Dispos. 2003 Nov;31(11):1369-77. doi: 10.1124/dmd.31.11.1369. [PubMed:14570769]
  3. Mancy A, Broto P, Dijols S, Dansette PM, Mansuy D: The substrate binding site of human liver cytochrome P450 2C9: an approach using designed tienilic acid derivatives and molecular modeling. Biochemistry. 1995 Aug 22;34(33):10365-75. [PubMed:7654690]
  4. Wang JF, Yan JY, Wei DQ, Chou KC: Binding of CYP2C9 with diverse drugs and its implications for metabolic mechanism. Med Chem. 2009 May;5(3):263-70. [PubMed:19442216]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid binding
Specific Function
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform glucuronidates bilirubin IX-alpha to form both the...
Gene Name
UGT1A1
Uniprot ID
P22309
Uniprot Name
UDP-glucuronosyltransferase 1-1
Molecular Weight
59590.91 Da
References
  1. 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. [PubMed:19515014]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Glucuronosyltransferase activity
Specific Function
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds.Its unique specificity for 3,4-catechol estrogens and estriol su...
Gene Name
UGT2B7
Uniprot ID
P16662
Uniprot Name
UDP-glucuronosyltransferase 2B7
Molecular Weight
60694.12 Da
References
  1. 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. [PubMed:19515014]

Drug created on June 13, 2005 07:24 / Updated on October 19, 2018 10:57