ESFLURBIPROFEN

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C15H13FO2
Molecular Weight	244.2609
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

C[C@H](C(O)=O)C1=CC(F)=C(C=C1)C2=CC=CC=C2

InChI

InChIKey=SYTBZMRGLBWNTM-JTQLQIEISA-N

InChI=1S/C15H13FO2/c1-10(15(17)18)12-7-8-13(14(16)9-12)11-5-3-2-4-6-11/h2-10H,1H3,(H,17,18)/t10-/m0/s1

HIDE SMILES / InChI

Description
Sources: http://adisinsight.springer.com/drugs/800006253 | http://www.taisho-holdings.co.jp/en/release/2016/2016012001-e.pdf | https://www.ncbi.nlm.nih.gov/pubmed/16134939https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/018766s015lbl.pdf | https://www.drugbank.ca/drugs/DB00712

Flurbiprofen, a propionic acid derivative, is a nonsteroidal anti-inflammatory drug that exhibits antiinflammatory, analgesic, and antipyretic activities in animal models. Flurbiprofen Tablets are indicated for relief of the signs and symptoms of rheumatoid arthritis and for relief of the signs and symptoms of osteoarthritis. It may also be used to treat pain associated with dysmenorrhea and mild to moderate pain accompanied by inflammation (e.g. bursitis, tendonitis, soft tissue trauma). Flurbiprofen may also be used topically prior to ocular surgery to prevent or reduce intraoperative miosis. Similar to other NSAIAs, the anti-inflammatory effect of flurbiprofen occurs via reversible inhibition of cyclooxygenase (COX), the enzyme responsible for the conversion of arachidonic acid to prostaglandin G2 (PGG2) and PGG2 to prostaglandin H2 (PGH2) in the prostaglandin synthesis pathway. This effectively decreases the concentration of prostaglandins involved in inflammation, pain, swelling and fever. Flurbiprofen is a non-selective COX inhibitor and inhibits the activity of both COX-1 and -2. It is also one of the most potent NSAIAs in terms of prostaglandin inhibitory activity.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Cyclooxygenase-1 127 Target ID: CHEMBL221 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15336599	Inhibitor 8297	0.11 µM [IC50]
Cyclooxygenase-2 196 Target ID: CHEMBL230 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24120370 \| https://www.ncbi.nlm.nih.gov/pubmed/15336599	Inhibitor 8297	6.46 µM [IC50]
Cyclooxygenase 89 Target ID: CHEMBL2094253 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26315084 \| https://www.selleckchem.com/products/flurbiprofen-axetil.html \| https://www.ncbi.nlm.nih.gov/pubmed/29540536	Inhibitor 8297
Cyclooxygenase-1 127 Target ID: CHEMBL221 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16455248 \| https://www.ncbi.nlm.nih.gov/pubmed/16134939	Inhibitor 8297	0.2 µM [IC50]
Cyclooxygenase-2 196 Target ID: CHEMBL230 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16134939	Inhibitor 8297	0.91 µM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Rheumatoid arthritis 316 Sources: https://www.drugs.com/pro/flurbiprofen-tablets.html	Primary	Approved 8429	Flurbiprofen Approved Use Flurbiprofen Tablets are indicated: • For relief of the signs and symptoms of rheumatoid arthritis. • For relief of the signs and symptoms of osteoarthritis. Launch Date 1988
Osteoarthritis 157 Sources: https://www.drugs.com/pro/flurbiprofen-tablets.html	Primary	Approved 8429	Flurbiprofen Approved Use Flurbiprofen Tablets are indicated: • For relief of the signs and symptoms of rheumatoid arthritis. • For relief of the signs and symptoms of osteoarthritis. Launch Date 1988
Osteoarthritis 157 Sources: http://www.taisho-holdings.co.jp/en/release/2016/2016012001-e.pdf	Primary	Approved 8429	LOQOA® Tape Approved Use LOQOA® Tape indicated for the treatment of osteoarthritis pain and inflammation. Launch Date 2015

C_max

Value	Dose	Co-administered	Analyte	Population
14 μg/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/018766s015lbl.pdf	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:		FLURBIPROFEN plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
19.67 μg/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/19808137	150 mg single, oral dose: 150 mg route of administration: Oral experiment type: SINGLE co-administered:		FLURBIPROFEN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

AUC

Value	Dose	Co-administered	Analyte	Population
83 μg × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/018766s015lbl.pdf	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:		FLURBIPROFEN plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
124.2 μg × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/19808137	150 mg single, oral dose: 150 mg route of administration: Oral experiment type: SINGLE co-administered:		FLURBIPROFEN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
7.5 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/018766s015lbl.pdf	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:		FLURBIPROFEN plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
4.77 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/19808137	150 mg single, oral dose: 150 mg route of administration: Oral experiment type: SINGLE co-administered:		FLURBIPROFEN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
	substrate 1037	substrate 1217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
OAT1 599 OAT3 642 MRP2 383 MRP4 204	CYP1A1 349 CYP2A6 543 CYP2B6 664 CYP2C19 991 UGT1A1 418 UGT1A3 422 UGT1A4 347 UGT1A6 307 UGT1A7 236 UGT1A8 283 UGT1A9 380 UGT1A10 291 UGT2B4 249 UGT2B7 389 UGT2B15 203 UGT2B17 213

Drug as perpetrator

Target	Modality	Activity
OAT1 603	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/22072415/	yes [IC50 0.615 uM]
OAT3 644	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/22072415/	yes [IC50 1.8 uM]
MRP4 238	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/26659924/	yes [IC50 10.6 uM]
MRP2 475	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/26659924/	yes [IC50 58.4 uM]

Drug as victim

Target	Modality	Activity	Clinical evidence
CYP1A1 349	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/8937439/ Page: 3.0	no
CYP2A6 543	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/8937439/ Page: 3.0	no
CYP2B6 664	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/8937439/ Page: 3.0	no
CYP2C19 991	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/8937439/ Page: 3.0	no
CYP2D6 1217	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/8937439/ Page: 3.0	no
UGT2B15 203	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/15843492/ Page: 4.0	no
UGT1A1 418	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/15843492/ Page: 1.0	yes
UGT1A10 291	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/15117964/ Page: 7.0	yes
UGT1A3 422	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/15843492/ Page: 1.0	yes
UGT1A4 347	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/15843492/	yes
UGT1A6 307	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/15843492/	yes
UGT1A7 236	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/15117964/ Page: 7.0	yes
UGT1A8 283	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/15117964/ Page: 7.0	yes
UGT1A9 380	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/15843492/ Page: 1.0	yes
UGT2B17 213	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/15843492/ Page: 4.0	yes
UGT2B4 249	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/15843492/ Page: 1.0	yes
UGT2B7 389	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/15843492/ Page: 1.0	yes
CYP2C9 1037	substrate 3367 Sources: https://www.ncbi.nlm.nih.gov/books/NBK537365/	yes	yes (co-administration study) Comment: Coadministration study with fluconazole (inhibitor of CYP2C9) increased AUCinf by 222%-299% after different visits of patients; Pharmacogenomic study: In patients who are known or suspected to be poor CYP2C9 metabolizers based on genotype or previous history/experience with other CYP2C9 substrates (such as warfarin and phenytoin), reduce the dose of flurbiprofen to avoid abnormally high plasma levels due to reduced metabolic clearance Sources: https://www.ncbi.nlm.nih.gov/books/NBK537365/

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:5130	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:5130
ChemicalBook	CB7465967	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB7465967
MolPort	MolPort-000-812-253	https://www.molport.com/shop/molecule-link/MolPort-000-812-253
eMolecules	538498	https://www.emolecules.com/cgi-bin/more?vid=538498

PubMed

Title	Date	PubMed
Arachidonic acid and PGE2 regulation of hepatic lipogenic gene expression.	1999 Jun	10357836
Reactive oxygen species are involved in the apoptosis induced by nonsteroidal anti-inflammatory drugs in cultured gastric cells.	1999 Nov 3	10594327
Effect of endogenous and exogenous prostaglandin E(2) on interleukin-1 beta-induced cyclooxygenase-2 expression in human airway smooth-muscle cells.	2000 Dec	11112151
R- and S-isomers of nonsteroidal anti-inflammatory drugs differentially regulate cytokine production.	2000 Jun	10903797
Prostaglandin E2 and the protein kinase A pathway mediate arachidonic acid induction of c-fos in human prostate cancer cells.	2000 Jun	10864209
Risk of upper gastrointestinal bleeding and perforation associated with low-dose aspirin as plain and enteric-coated formulations.	2001	11228592
Review: uveitis and immunosuppressive drugs.	2001 Apr	11324985
Vasorelaxant effect of nitric oxide releasing steroidal and nonsteroidal anti-inflammatory drugs.	2001 Aug	11487511
Minimal in vivo activation of CYP2C9-mediated flurbiprofen metabolism by dapsone.	2001 Aug	11457649
Palladium-catalyzed alpha-arylation of esters.	2001 Aug 22	11506555
Inhibition of NF-kappaB and AP-1 activation by R- and S-flurbiprofen.	2001 Jan	11099482
Using evidence from different sources: an example using paracetamol 1000 mg plus codeine 60 mg.	2001 Jan 10	11231885
Dapsone activation of CYP2C9-mediated metabolism: evidence for activation of multiple substrates and a two-site model.	2001 Jul	11408370
NO-flurbiprofen attenuates excitotoxin-induced brain inflammation, and releases nitric oxide in the brain.	2001 Jun	11459126
Screening procedure for detection of non-steroidal anti-inflammatory drugs and their metabolites in urine as part of a systematic toxicological analysis procedure for acidic drugs and poisons by gas chromatography-mass spectrometry after extractive methylation.	2001 May-Jun	11386636
Retrospective analysis of drug-induced urticaria and angioedema: a survey of 2287 patients.	2001 Nov	11792017
Differential effects of the nonsteroidal antiinflammatory drug flurbiprofen and its nitric oxide-releasing derivative, nitroflurbiprofen, on prostaglandin E(2), interleukin-1beta, and nitric oxide synthesis by activated microglia.	2001 Nov 15	11746392
Synthesis and receptor docking studies of N-substituted indole-2-carboxylic acid esters as a search for COX-2 selective enzyme inhibitors.	2001 Sep	11672885
Inhibition of bone resorption in vitro and prevention of ovariectomy-induced bone loss in vivo by flurbiprofen nitroxybutylester (HCT1026).	2001 Sep	11592384
Pathogenic importance of intestinal hypermotility in NSAID-induced small intestinal damage in rats.	2002	12379813
Nitric-oxide releasing molecules: a new class of drugs with several major indications.	2002	11864065
Affinity capillary electrophoresis using a low-concentration additive with the consideration of relative mobilities.	2002 Apr 15	11985325
[The effectiveness of perioperative intravenous flurbiprofen in minor ear, neck and nose surgery].	2002 Aug	12229133
Rapid and simple quantitative assay method for diastereomeric flurbiprofen glucuronides in the incubation mixture.	2002 Aug 25	12127333
Molecular modelling of the differential interaction between several non-steroidal anti-inflammatory drugs and human prostaglandin endoperoxide H synthase-2 (h-PGHS-2).	2002 Jan	11858641
Characterization of the bone-resorptive effect of interleukin-11 in cultured mouse calvarial bones.	2002 Jul	12110441
Prediction of poly(ethylene) glycol-drug eutectic compositions using an index based on the van't Hoff equation.	2002 Mar	11934239
Mechanism of in vitro release kinetics of flurbiprofen loaded ethylcellulose micropellets.	2002 May-Jun	12230246
A nitric oxide-donating flurbiprofen derivative reduces neuroinflammation without interacting with galantamine in the rat.	2002 Oct 25	12398920
Aging Enables Ca2+ Overload and Apoptosis Induced by Amyloid-β Oligomers in Rat Hippocampal Neurons: Neuroprotection by Non-Steroidal Anti-Inflammatory Drugs and R-Flurbiprofen in Aging Neurons.	2016 Jul 22	27447424
Effect of oxycodone hydrochloride combined with flurbiprofen axetil for intravenous patient-controlled analgesia in lower abdominal patients: A randomized trial.	2018 Feb	29443767
[Effect of multimodal analgesia using periprostatic nerve block anesthesia combined with flurbiprofen in transperineal template-guided prostate biopsy].	2019 Jun 1	31142067

Patents

Sample Use Guides

In Vivo Use Guide

Loqoa® is available as a patch formulation, containing 40 mg of Esflurbiprofen. The recommended dose is applied to the lesion area once daily. Do not apply more than two patches simultaneously.

Route of Administration: Topical

In Vitro Use Guide

At 100 uM concentration Esflurbiprofen (S-Flurbiprofen) demonstrated 37% inhibition of Abeta42 in SH-SY5Y cells and 65% in HEK cells.

Name

Type

Language

ESFLURBIPROFEN

Official Name

English

FLURBIPROFEN, (S)-

Common Name

English

BTS-24332

Code

English

esflurbiprofen [INN]

Common Name

English

ESFLURBIPROFEN [JAN]

Common Name

English

BTS 24332

Code

English

(S)-2-FLUORO-.ALPHA.-METHYL-4-BIPHENYLACETIC ACID

Systematic Name

English

Esflurbiprofen [WHO-DD]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C257