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=CC2=C(OC(=N2)C3=CC=C(Cl)C=C3)C=C1

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	C16H12ClNO3
Molecular Weight	301.724
Charge	0
Count

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

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

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 49 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 8297		149.0 µM [IC50]
Bile salt export pump 15 Target ID: CHEMBL2073674 Sources: https://www.ncbi.nlm.nih.gov/pubmed/21965623	Inhibitor 8297		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) n = 20 Health Status: unhealthy Condition: arthritis Age Group: 35 years (rage: 26-43 years) Sex: M+F Population Size: 20 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) n = 5 Health Status: unhealthy Age Group: 54,9 years (range: 18-86 years) Sex: M+F Population Size: 5 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) n = 20 Health Status: unhealthy Condition: arthritis Age Group: 35 years (rage: 26-43 years) Sex: M+F Population Size: 20 Sources: https://pubmed.ncbi.nlm.nih.gov/6407402/

Overview

CYP3A4	CYP2C9	CYP2D6	hERG

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
		CYP1A1 108 CYP1A2 701 CYP4A1 17

Drug as perpetrator

Target	Modality	Activity
CYP1A1 218	inducer 1573 Sources: https://pubmed.ncbi.nlm.nih.gov/2069584/	yes
CYP1A2 1692	inducer 1573 Sources: https://pubmed.ncbi.nlm.nih.gov/2069584/	yes
CYP4A1 25	inducer 1573 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
Nonsteroid anti-inflammatory agents: regulators of the phagocytic secretion of lysosomal enzymes from guinea-pig neutrophils.	1978 Nov	712644
A comparative study of benoxaprofen and ibuprofen in osteoarthritis in general practice.	1980	6993669
Long-term safety of benoxaprofen.	1980	6993665
Toxic optic neuropathy caused by benoxaprofen.	1981 Jul 18	6789963
An update on long-term efficacy and safety with benoxaprofen.	1982	7084281
The preferential inhibition of 5-lipoxygenase product formation by benoxaprofen.	1983 Jan	6131964
Benoxaprofen improves psoriasis. A double-blind study.	1983 Jul	6407402
The aetiology of psoriasis: clues provided by benoxaprofen.	1983 Jul	6305387
[Vasculitis caused by benoxaprofen].	1983 Oct 8	6645654
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 Apr 15	6430271
Effects of benoxaprofen on human neutrophil function.	1984 Jun	6737371
Benoxaprofen photosensitization of cell membrane disruption.	1984 Mar	6699424
Effects of some non-steroidal anti-inflammatory drugs and other agents on cyclooxygenase and lipoxygenase activities in some enzyme preparations.	1985 Jun	3928952
Meclofenamate sodium is an inhibitor of both the 5-lipoxygenase and cyclooxygenase pathways of the arachidonic acid cascade in vitro.	1986 Aug	3020588
Primary biliary cirrhosis after benoxaprofen.	1986 Jul 26	3089471
Interaction of benoxaprofen with rat erythrocytes: effects on oxidative metabolism and membrane ATPase activities.	1986 Nov	2947294
Benoxaprofen photosensitization of phospholipase activation in mammalian cells in culture.	1986 Sep	3095956
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
Simple procedure for measuring the pharmacodynamics and analgesic potential of lipoxygenase inhibitors.	1988 Dec	3145369
Species difference of 5-lipoxygenase derived from polymorphonuclear leukocytes on sensitivity to drugs.	1989 May	2724698
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 Jun 21	2069584
Complementary deoxyribonucleic acid cloning and expression of a human liver uridine diphosphate-glucuronosyltransferase glucuronidating carboxylic acid-containing drugs.	1993 Jan	8423545
A systematic review of NSAIDs withdrawn from the market due to hepatotoxicity: lessons learned from the bromfenac experience.	2006 Apr	16456879
Carboxylic acid drug-induced DNA nicking in HEK293 cells expressing human UDP-glucuronosyltransferases: role of acyl glucuronide metabolites and glycation pathways.	2007 Oct	17880178
Glucuronidation and covalent protein binding of benoxaprofen and flunoxaprofen in sandwich-cultured rat and human hepatocytes.	2009 Dec	19773537
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 Jan	24085192

Patents

Substance Class	Chemical Created by `admin` on `Sat Dec 16 10:24:30 GMT 2023` Edited by `admin` on `Sat Dec 16 10:24:30 GMT 2023`
Record UNII	825YBQ31XF
Record Status	`Validated (UNII)`
Record Version

Download

Name

Type

Language

BENOXAPROFEN AMMONIUM

Common Name

English

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

Systematic Name

English

Code System Code Type Description

ECHA (EC/EINECS)

274-298-8