BENOXAPROFEN AMMONIUM

US Previously Marketed

First approved in 1982

Details

Stereochemistry	RACEMIC
Molecular Formula	C16H11ClNO3.H4N
Molecular Weight	318.755
Optical Activity	( + / - )
Defined Stereocenters	0 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[NH4+].CC(C([O-])=O)C1=CC=C2OC(=NC2=C1)C3=CC=C(Cl)C=C3

InChI

InChIKey=DNGLOBZMXKFACM-UHFFFAOYSA-N

InChI=1S/C16H12ClNO3.H3N/c1-9(16(19)20)11-4-7-14-13(8-11)18-15(21-14)10-2-5-12(17)6-3-10;/h2-9H,1H3,(H,19,20);1H3

HIDE SMILES / InChI

Molecular Formula	H3N
Molecular Weight	17.0305
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Molecular Formula	C16H12ClNO3
Molecular Weight	301.724
Charge	0
Count

Stereochemistry	RACEMIC
Additional Stereochemistry	No
Defined Stereocenters	0 / 1
E/Z Centers	0
Optical Activity	( + / - )

Description
Sources: https://www.federalregister.gov/documents/2013/06/04/2013-13053/eli-lilly-and-co-withdrawal-of-approval-of-a-new-drug-application-for-oraflex | https://www.bmj.com/content/bmj/285/6340/459.full.pdf

BENOXAPROFEN is an anti-inflammatory drug indicated for the treatment of arthritis. It was marketed under the brand name ORAFLEX® in the US and as OPREN® in Europe by Eli Lilly and Company. In 1982 Eli Lilly voluntarily withdrew BENOXAPROFEN from the market due to postmarketing reports of severe liver toxicity in patients who took it.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Arachidonate 5-lipoxygenase 52 Target ID: CHEMBL215 Sources: http://drugcentral.org/drugcard/311\|https://www.ncbi.nlm.nih.gov/pubmed/2988019\|https://www.ncbi.nlm.nih.gov/pubmed/2572437\|https://www.ncbi.nlm.nih.gov/pubmed/6131964\|https://www.genome.jp/dbget-bin/www_bget?dr:D03080	Inhibitor 8504		149.0 µM [IC50]
Bile salt export pump 15 Target ID: CHEMBL2073674 Sources: https://www.ncbi.nlm.nih.gov/pubmed/21965623	Inhibitor 8504		99.1 µM [IC50]

C_max

Value	Dose	Co-administered	Analyte	Population
43 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/303114	100 mg 2 times / day multiple, oral dose: 100 mg route of administration: Oral experiment type: MULTIPLE co-administered:		BENOXAPROFEN plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
94 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/6930484	300 mg 2 times / day steady-state, rectal dose: 300 mg route of administration: Rectal experiment type: STEADY-STATE co-administered:		BENOXAPROFEN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
503 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/303114	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:		BENOXAPROFEN plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
4.84 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/303114	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:		BENOXAPROFEN plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
38 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/6930484	300 mg 2 times / day steady-state, rectal dose: 300 mg route of administration: Rectal experiment type: STEADY-STATE co-administered:		BENOXAPROFEN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
600 mg 1 times / day steady, oral Recommended Dose: 600 mg, 1 times / day Route: oral Route: steady Dose: 600 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/6407402/	unhealthy, 35 years (rage: 26-43 years) Health Status: unhealthy Age Group: 35 years (rage: 26-43 years) Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/6407402/	Disc. AE: Photosensitivity... AEs leading to discontinuation/dose reduction: Photosensitivity (11 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/6407402/
900 mg 1 times / day steady, oral Highest studied dose Dose: 900 mg, 1 times / day Route: oral Route: steady Dose: 900 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/6803978	unhealthy, 54,9 years (range: 18-86 years) Health Status: unhealthy Age Group: 54,9 years (range: 18-86 years) Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/6803978	Sources: https://pubmed.ncbi.nlm.nih.gov/6803978

AEs

AE	Significance	Dose	Population
Photosensitivity	11 patient Disc. AE	600 mg 1 times / day steady, oral Recommended Dose: 600 mg, 1 times / day Route: oral Route: steady Dose: 600 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/6407402/	unhealthy, 35 years (rage: 26-43 years) Health Status: unhealthy Age Group: 35 years (rage: 26-43 years) Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/6407402/

Overview

CYP3A4	CYP2C9	CYP2D6	hERG

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
		CYP1A1 151 CYP1A2 832 CYP4A1 17

Drug as perpetrator

Target	Modality	Activity
CYP1A1 272	inducer 1966 Sources: https://pubmed.ncbi.nlm.nih.gov/2069584/	yes
CYP1A2 2333	inducer 1966 Sources: https://pubmed.ncbi.nlm.nih.gov/2069584/	yes
CYP4A1 25	inducer 1966 Sources: https://pubmed.ncbi.nlm.nih.gov/2069584/	yes

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:76114	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:76114
eMolecules	35875742	https://www.emolecules.com/cgi-bin/more?vid=35875742

PubMed

Title	Date	PubMed
A correlation between the in vitro drug toxicity of drugs to cell lines that express human P450s and their propensity to cause liver injury in humans.	2014-01	24085192
Glucuronidation and covalent protein binding of benoxaprofen and flunoxaprofen in sandwich-cultured rat and human hepatocytes.	2009-12	19773537
Carboxylic acid drug-induced DNA nicking in HEK293 cells expressing human UDP-glucuronosyltransferases: role of acyl glucuronide metabolites and glycation pathways.	2007-10	17880178
A systematic review of NSAIDs withdrawn from the market due to hepatotoxicity: lessons learned from the bromfenac experience.	2006-04	16456879
Complementary deoxyribonucleic acid cloning and expression of a human liver uridine diphosphate-glucuronosyltransferase glucuronidating carboxylic acid-containing drugs.	1993-01	8423545
Induction of the cytochrome P450 I and IV families and peroxisomal proliferation in the liver of rats treated with benoxaprofen. Possible implications in its hepatotoxicity.	1991-06-21	2069584
Species difference of 5-lipoxygenase derived from polymorphonuclear leukocytes on sensitivity to drugs.	1989-05	2724698
Simple procedure for measuring the pharmacodynamics and analgesic potential of lipoxygenase inhibitors.	1988-12	3145369
In vitro inhibition of leukotriene B4 formation by exogeneous 5-lipoxygenase inhibitors is associated with enhanced generation of 15-hydroxy-eicosatetraenoic acid (15-HETE) by human neutrophils.	1988	2849922
Interaction of benoxaprofen with rat erythrocytes: effects on oxidative metabolism and membrane ATPase activities.	1986-11	2947294
Benoxaprofen photosensitization of phospholipase activation in mammalian cells in culture.	1986-09	3095956
Meclofenamate sodium is an inhibitor of both the 5-lipoxygenase and cyclooxygenase pathways of the arachidonic acid cascade in vitro.	1986-08	3020588
Primary biliary cirrhosis after benoxaprofen.	1986-07-26	3089471
Effects of some non-steroidal anti-inflammatory drugs and other agents on cyclooxygenase and lipoxygenase activities in some enzyme preparations.	1985-06	3928952
Effects of benoxaprofen on human neutrophil function.	1984-06	6737371
Inhibition of steroid production in Leydig cells by non-steroidal anti-inflammatory and related compounds: evidence for the involvement of lipoxygenase products in steroidogenesis.	1984-04-15	6430271
Benoxaprofen photosensitization of cell membrane disruption.	1984-03	6699424
[Vasculitis caused by benoxaprofen].	1983-10-08	6645654
Benoxaprofen improves psoriasis. A double-blind study.	1983-07	6407402
The aetiology of psoriasis: clues provided by benoxaprofen.	1983-07	6305387
The preferential inhibition of 5-lipoxygenase product formation by benoxaprofen.	1983-01	6131964
An update on long-term efficacy and safety with benoxaprofen.	1982	7084281
Toxic optic neuropathy caused by benoxaprofen.	1981-07-18	6789963
A comparative study of benoxaprofen and ibuprofen in osteoarthritis in general practice.	1980	6993669
Long-term safety of benoxaprofen.	1980	6993665
Nonsteroid anti-inflammatory agents: regulators of the phagocytic secretion of lysosomal enzymes from guinea-pig neutrophils.	1978-11	712644

Patents

Substance Class	Chemical Created by `admin` on `Mon Mar 31 23:13:08 GMT 2025` Edited by `admin` on `Mon Mar 31 23:13:08 GMT 2025`
Record UNII	825YBQ31XF
Record Status	`Validated (UNII)`
Record Version

Download

Name

Type

Language

5-BENZOXAZOLEACETIC ACID, 2-(4-CHLOROPHENYL)-.ALPHA.-METHYL-, AMMONIUM SALT (1:1)

Preferred Name

English

BENOXAPROFEN AMMONIUM

Common Name

English

Code System Code Type Description

ECHA (EC/EINECS)

274-298-8