BUFEXAMAC

Details

Stereochemistry	ACHIRAL
Molecular Formula	C12H17NO3
Molecular Weight	223.2683
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CCCCOC1=CC=C(CC(=O)NO)C=C1

InChI

InChIKey=MXJWRABVEGLYDG-UHFFFAOYSA-N

InChI=1S/C12H17NO3/c1-2-3-8-16-11-6-4-10(5-7-11)9-12(14)13-15/h4-7,15H,2-3,8-9H2,1H3,(H,13,14)

HIDE SMILES / InChI

Description
Sources: http://www.who.int/medicines/publications/druginformation/DrugInfo2010_Vol24-2.pdf
Curator's Comment: Description was created based on several sources, including http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/referrals/Bufexamac/human_referral_000209.jsp&mid=WC0b01ac05805c516f | https://www.ncbi.nlm.nih.gov/pubmed/14607020 | https://www.ncbi.nlm.nih.gov/pubmed/25751058 | https://www.ncbi.nlm.nih.gov/pubmed/21258344 | https://www.ncbi.nlm.nih.gov/pubmed/27126280

Bufexamac is a nonsteroidal antiinflammatory drug (NSAID) used in topical formulations to treat dermatological diseases (eczema and dermatitis) and proctological conditions (haemorrhoids and anal fissure). Bufexamac-containing medicines have been available in EU Member States since the 1970s. In 2010 European Medicines Agency recommends revocation of marketing authorisations for bufexamac due to high risk of contact allergies. The phenolic bufexamac decomposition products could be the reason for its eczema-provoking properties frequently described in the literature. Bufexamac is a class IIb histone deacetylase (HDAC6, HDAC10) inhibitor. Bufexamac also triggered an HDAC6-independent, hypoxia-like response by stabilizing Hypoxia-inducible factor 1-alpha, providing a possible mechanistic explanation of its adverse, pro-inflammatory effects. Bufexamac was capable of specifically inhibiting leukotriene A4 hydrolase and attenuating lung inflammation in acute lung injury mouse model.

Approval Year

Targets

Primary Target	Pharmacology	Potency
Oxidative Stress 160 Target ID: WP408 Sources: https://www.ncbi.nlm.nih.gov/pubmed/14607020	Inhibitor 8297
Histone deacetylase 6 27 Target ID: CHEMBL1865 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25751058 \| https://www.ncbi.nlm.nih.gov/pubmed/21258344	Inhibitor 8297	10.7 µM [Kd]
Histone deacetylase 10 10 Target ID: CHEMBL5103 Sources: https://www.ncbi.nlm.nih.gov/pubmed/21258344	Inhibitor 8297	12.3 µM [Kd]
Hypoxia-inducible factor 1 alpha 17 Target ID: CHEMBL4261 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25751058	Activator 1430
Leukotriene A4 hydrolase 4 Target ID: CHEMBL4618 Sources: https://www.ncbi.nlm.nih.gov/pubmed/27126280	Inhibitor 8297	15.86 µM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Eczema 46 Sources: https://www.chemotechnique.se/get_pdf.php?l=en&p=682	Primary	Withdrawn	BUFEXAMAC Approved Use Bufexamac are used for the treatment of subacute and chronic eczema of the skin, including atopic eczema, as well as sunburn and other minor burns, and itching. Suppositories containing bufexamac in combination with local anaesthetics are used against haemorrhoids.
Haemorrhoids 6 Sources: https://www.chemotechnique.se/get_pdf.php?l=en&p=682	Primary	Withdrawn	BUFEXAMAC Approved Use Bufexamac are used for the treatment of subacute and chronic eczema of the skin, including atopic eczema, as well as sunburn and other minor burns, and itching. Suppositories containing bufexamac in combination with local anaesthetics are used against haemorrhoids.
Acute lung injury 20 Sources: https://www.ncbi.nlm.nih.gov/pubmed/27126280	Primary	Preclinical	Unknown Approved Use Unknown

PubMed

Title	Date	PubMed
Skin sensitizing properties of arylalcanoic acids and their analogues.	1979 Sep	509935
Effects of intra-articular injections of bufexamac suspension in healthy horses.	2001 Oct	11592331
Allergic contact dermatitis with spreading over extensive regions due to topical use of 5% bufexamac ointment.	2004 Feb	15160871
Frequency of contact allergy in German children and adolescents patch tested between 1995 and 2002: results from the Information Network of Departments of Dermatology and the German Contact Dermatitis Research Group.	2004 Sep	15479199
Screening for new antioxidative compounds for topical administration using skin lipid model systems.	2005 Sep 15	16401395
Allergic contact dermatitis to topical drugs--epidemiological risk assessment.	2008 Aug	18383004
[Facial allergic contact dermatitis. Data from the IVDK and review of literature].	2009 Jan	19099269
[Bufexamac-induced pigmented purpuric eruption].	2009 May	19093092
Contact dermatitis due to topical drugs.	2009 Oct	19834431

Patents

Sample Use Guides

In Vivo Use Guide

Apply 5% cream to affected areas.

Route of Administration: Topical

In Vitro Use Guide

Treatment of peripheral blood mononuclear cells with bufexamac inhibits the secretion of IFN-α (EC50 = 8.9 uM)

Name

Type

Language

BUFEXAMAC

Official Name

English

PARADERM

Common Name

English

BUFEXAMAC [JAN]

Common Name

English

ANDERM

Common Name

English

CP-1044-J3

Code

English

Bufexamac [WHO-DD]

Common Name

English

BUFEXAMAC [EP MONOGRAPH]

Common Name

English

CP 1044 J3

Code

English

bufexamac [INN]

Common Name

English

BUFEXAMAC [MART.]

Common Name

English

NSC-758153

Code

English

PARFENAC

Common Name

English

2-(P-BUTOXYPHENYL)-ACETOHYDROXAMIC ACID

Common Name

English

BUFEXAMAC [EP IMPURITY]

Common Name

English

Classification Tree Code System Code

WHO-VATC

QM02AA09