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

Molecular Formula	C12H17NO3
Molecular Weight	223.2683
Charge	0
Count

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

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
[Epidemiologic surveillance of contact allergens. The "monitoring series" of IVDK (Information Network ofDermatologic Clinics for Detection and Scientific Evaluation of Contact Allergy].	2003 Aug	12942188
An integrative approach to eczema (atopic dermatitis).	2003 Jan-Feb	12597676
[Severe allergic contact dermatitis with generalized spread due to bufexamac presenting as the "baboon" syndrome].	2003 Mar 14	12635026
Examinations of the antioxidative properties of the topically administered drug bufexamac reveal new insights into its mechanism of action.	2003 Oct	14607020
Allergic contact dermatitis with spreading over extensive regions due to topical use of 5% bufexamac ointment.	2004 Feb	15160871
[Facial allergic contact dermatitis. Data from the IVDK and review of literature].	2009 Jan	19099269
A systematic review of randomized controlled trials of treatments for inherited forms of epidermolysis bullosa.	2009 Jan	18828848
Chemoproteomics profiling of HDAC inhibitors reveals selective targeting of HDAC complexes.	2011 Mar	21258344

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)

Substance Class	Chemical Created by `admin` on `Sat Dec 16 16:04:43 UTC 2023` Edited by `admin` on `Sat Dec 16 16:04:43 UTC 2023`
Record UNII	4T3C38J78L
Record Status	`Validated (UNII)`
Record Version

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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