DAPSONE

First approved in 1955

Details

Stereochemistry	ACHIRAL
Molecular Formula	C12H12N2O2S
Molecular Weight	248.3024
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

c1cc(ccc1N)S(=O)(=O)c2ccc(cc2)N

InChI

InChIKey=MQJKPEGWNLWLTK-UHFFFAOYSA-N

InChI=1S/C12H12N2O2S/c13-9-1-5-11(6-2-9)17(15,16)12-7-3-10(14)4-8-12/h1-8H,13-14H2

HIDE SMILES / InChI

Description
Sources: http://escholarship.org/uc/item/30m4b5kr
Curator's Comment:: description was created based on several sources, including http://www.accessdata.fda.gov/drugsatfda_docs/nda/2005/021794s000_MicroR.pdf

Dapsone was synthesized in 1908 by Fromm and Wittmann. The drug was approved by FDA for the treatment of such conditions as acne vulgaris, leprosy and dermatitis herpetiformis, also the drug is used off-label for many skin diseases. Although the exact mechanism of dapsone action is unknown, it is speculated that it acts as both anti-inflammatory and antimicrobial agent. It was demonstrated that dapsone suppresses ROS generation, inhibits neutrophil myeloperoxidase and eosinophil peroxidase and also inhibits bacterial dihydropteroate synthase.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Bacterial dihydropteroate synthase 42 Target ID: CHEMBL2364668 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24310318	Inhibitor 7701	Leprosy Dermatitis herpetiformis Acne vulgaris

Conditions

Condition	Modality	Targets	Highest Phase	Product
Acne vulgaris 32 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/021794s013lbl.pdf	Curative	Bacterial dihydropteroate synthase	Approved 7997	ACZONE Approved Use Gel is indicated for the topical treatment of acne vulgaris. Launch Date -473385600000
Dermatitis herpetiformis 9 Sources: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=7fc98c9b-b17a-f66f-055b-259207ad9504	Curative	Bacterial dihydropteroate synthase	Approved 7997	DAPSONE Approved Use Dermatitis herpetiformis: (D.H.) Leprosy: All forms of leprosy except for cases of proven Dapsone resistance. Launch Date 299808000000
Leprosy 5 Sources: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=7fc98c9b-b17a-f66f-055b-259207ad9504	Curative	Bacterial dihydropteroate synthase	Approved 7997	DAPSONE Approved Use Dermatitis herpetiformis: (D.H.) Leprosy: All forms of leprosy except for cases of proven Dapsone resistance. Launch Date 299808000000

C_max

Value	Dose	Co-administered	Analyte	Population
1375 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17655376	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:		DAPSONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
19.7 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17655376	110 mg 2 times / day steady-state, topical dose: 110 mg route of administration: Topical experiment type: STEADY-STATE co-administered:		DAPSONE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Analyte	Population
221.52 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17655376	110 mg 2 times / day steady-state, topical dose: 110 mg route of administration: Topical experiment type: STEADY-STATE co-administered:	DAPSONE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
22783 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17655376	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:	DAPSONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
415 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17655376	110 mg 2 times / day steady-state, topical dose: 110 mg route of administration: Topical experiment type: STEADY-STATE co-administered:	DAPSONE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
52641 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17655376	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:	DAPSONE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
20.6 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17655376	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:		DAPSONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
42 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17655376	110 mg 2 times / day steady-state, topical dose: 110 mg route of administration: Topical experiment type: STEADY-STATE co-administered:		DAPSONE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
10% REVIEW https://pubmed.ncbi.nlm.nih.gov/3530584	unknown, unknown		DAPSONE plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
300 mg 1 times / week multiple, oral Highest studied dose Dose: 300 mg, 1 times / week Route: oral Route: multiple Dose: 300 mg, 1 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/7979291	unhealthy, 38 Health Status: unhealthy Age Group: 38 Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/7979291	Disc. AE: Anemia, Rash... AEs leading to discontinuation/dose reduction: Anemia (11.1%) Rash (11.1%) Fever (11.1%) Sources: https://pubmed.ncbi.nlm.nih.gov/7979291
200 mg 1 times / week multiple, oral MTD Dose: 200 mg, 1 times / week Route: oral Route: multiple Dose: 200 mg, 1 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/7979291	unhealthy, 38 Health Status: unhealthy Age Group: 38 Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/7979291	Disc. AE: Vomiting, Fever... AEs leading to discontinuation/dose reduction: Vomiting (14.3%) Fever (14.3%) Sources: https://pubmed.ncbi.nlm.nih.gov/7979291
10 g single, oral Overdose Dose: 10 g Route: oral Route: single Dose: 10 g Sources: https://pubmed.ncbi.nlm.nih.gov/6660028	unhealthy, 45 Health Status: unhealthy Age Group: 45 Sex: M Sources: https://pubmed.ncbi.nlm.nih.gov/6660028	Disc. AE: Cyanosis, Methaemoglobinaemia... AEs leading to discontinuation/dose reduction: Cyanosis (acute) Methaemoglobinaemia Haemolysis Sources: https://pubmed.ncbi.nlm.nih.gov/6660028

AEs

AE	Significance	Dose	Population
Anemia	11.1% Disc. AE	300 mg 1 times / week multiple, oral Highest studied dose Dose: 300 mg, 1 times / week Route: oral Route: multiple Dose: 300 mg, 1 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/7979291	unhealthy, 38 Health Status: unhealthy Age Group: 38 Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/7979291
Fever	11.1% Disc. AE	300 mg 1 times / week multiple, oral Highest studied dose Dose: 300 mg, 1 times / week Route: oral Route: multiple Dose: 300 mg, 1 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/7979291	unhealthy, 38 Health Status: unhealthy Age Group: 38 Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/7979291
Rash	11.1% Disc. AE	300 mg 1 times / week multiple, oral Highest studied dose Dose: 300 mg, 1 times / week Route: oral Route: multiple Dose: 300 mg, 1 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/7979291	unhealthy, 38 Health Status: unhealthy Age Group: 38 Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/7979291
Fever	14.3% Disc. AE	200 mg 1 times / week multiple, oral MTD Dose: 200 mg, 1 times / week Route: oral Route: multiple Dose: 200 mg, 1 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/7979291	unhealthy, 38 Health Status: unhealthy Age Group: 38 Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/7979291
Vomiting	14.3% Disc. AE	200 mg 1 times / week multiple, oral MTD Dose: 200 mg, 1 times / week Route: oral Route: multiple Dose: 200 mg, 1 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/7979291	unhealthy, 38 Health Status: unhealthy Age Group: 38 Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/7979291
Haemolysis	Disc. AE	10 g single, oral Overdose Dose: 10 g Route: oral Route: single Dose: 10 g Sources: https://pubmed.ncbi.nlm.nih.gov/6660028	unhealthy, 45 Health Status: unhealthy Age Group: 45 Sex: M Sources: https://pubmed.ncbi.nlm.nih.gov/6660028
Methaemoglobinaemia	Disc. AE	10 g single, oral Overdose Dose: 10 g Route: oral Route: single Dose: 10 g Sources: https://pubmed.ncbi.nlm.nih.gov/6660028	unhealthy, 45 Health Status: unhealthy Age Group: 45 Sex: M Sources: https://pubmed.ncbi.nlm.nih.gov/6660028
Cyanosis	acute Disc. AE	10 g single, oral Overdose Dose: 10 g Route: oral Route: single Dose: 10 g Sources: https://pubmed.ncbi.nlm.nih.gov/6660028	unhealthy, 45 Health Status: unhealthy Age Group: 45 Sex: M Sources: https://pubmed.ncbi.nlm.nih.gov/6660028

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1470	substrate 865 activator 20

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	CYP2C8 586 CYP2E1 567

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
CYP2C9 1362	activator 171 Sources: https://pubmed.ncbi.nlm.nih.gov/11408370/	likely

Drug as victim

Target	Modality	Activity
CYP2C8 586	substrate 2752 Sources: https://pubmed.ncbi.nlm.nih.gov/19998329/	yes
CYP2C9 865	substrate 2752 Sources: https://pubmed.ncbi.nlm.nih.gov/19998329/	yes
CYP2E1 567	substrate 2752 Sources: https://pubmed.ncbi.nlm.nih.gov/19998329/	yes
CYP3A4 1470	substrate 2752 Sources: https://pubmed.ncbi.nlm.nih.gov/19998329/	yes

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:4325	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:4325
MolPort	MolPort-001-780-172	https://www.molport.com/shop/molecule-link/MolPort-001-780-172
ZINC	ZINC000000006310	http://zinc15.docking.org/substances/ZINC000000006310

PubMed

Title	Date	PubMed
Evaluation of the sulfones and streptomycin in experimental tuberculosis.	1949 Dec 14	15398779
Dapsone suppresses integrin-mediated neutrophil adherence function.	1992 Feb	1732379
Treatment of experimental pneumocystosis: review of 7 years of experience and development of a new system for classifying antimicrobial drugs.	1992 Sep	1416885
The IL-8 release from cultured human keratinocytes, mediated by antibodies to bullous pemphigoid autoantigen 180, is inhibited by dapsone.	2001 Apr	11359455
Antimicrobial activities of dihydrofolate reductase inhibitors, used singly or in combination with dapsone, against Mycobacterium ulcerans.	2001 Jan	11152437
A trial of proguanil-dapsone in comparison with sulfadoxine-pyrimethamine for the clearance of Plasmodium falciparum infections in Tanzania.	2001 Jul-Aug	11579891
Chlorproguanil-dapsone for treatment of drug-resistant falciparum malaria in Tanzania.	2001 Oct 13	11675058
[A 50-year history of new drugs in Japan: the developments of antileprosy drugs and their epidemiological aspects].	2002	12412600
[Bioavailability of isoniazid in healthy volunteers--fast and slow INH acetylators].	2002	12271964
Dapsone-induced cholestasis and impairment of bile salt output in the rat.	2002 Apr 15	11996898
In vitro activities of pentamidine, pyrimethamine, trimethoprim, and sulfonamides against Aspergillus species.	2002 Jun	12019133
Cytochrome P450 1A1/2 induction by antiparasitic drugs: dose-dependent increase in ethoxyresorufin O-deethylase activity and mRNA caused by quinine, primaquine and albendazole in HepG2 cells.	2002 Nov	12451431
[Dapsone-induced sensory peripheral neuropathy].	2003 Apr	12843858
Dapsone induced cholangitis as a part of dapsone syndrome: a case report.	2003 Aug 11	12911838
Unfolding of phonetic information over time: a database of Dutch diphone perception.	2003 Jan	12558292
[Helicobacter pylori eradication based upon a drug sensitivity test effectively increased platelet count in a patient with refractory idiopathic thrombocytopenic purpura].	2003 Jul	12931570
Synthesis and evaluation of analogues of Congo red as potential compounds against transmissible spongiform encephalopathies.	2003 Jun	12832128
[Treatment of relapsing polychondritis].	2003 Mar	12708032
A near fatal case of the dapsone hypersensitivity syndrome in a patient with urticarial vasculitis.	2003 Sep	12950336
Identification of human cytochrome P(450)s that metabolise anti-parasitic drugs and predictions of in vivo drug hepatic clearance from in vitro data.	2003 Sep	12920490
A case of refractory bullous pemphigoid with plasmapheresis-associated thrombopenia: efficacy of pulsed intravenous cyclophosphamide therapy.	2004 Aug	15492438
Folate-synthesizing enzyme system as target for development of inhibitors and inhibitor combinations against Candida albicans-synthesis and biological activity of new 2,4-diaminopyrimidines and 4'-substituted 4-aminodiphenyl sulfones.	2004 Jan 1	14695838
Simultaneous determination of beta-blocking agents and diuretics in doping analysis by liquid chromatography/mass spectrometry with scan-to-scan polarity switching.	2005	15584083
Dapsone impairs the bile salt-independent fraction of bile flow in rats: Possible involvement of its N-hydroxylated metabolite.	2005 Jul 1	15863252
Aplastic anaemia associated with multidrug therapy (dapsone, rifampicin and clofazimine) in a patient with lepromatous leprosy.	2005 Jun	16038251
Prediction of genotoxicity of chemical compounds by statistical learning methods.	2005 Jun	15962942
Dapsone suppresses human neutrophil superoxide production and elastase release in a calcium-dependent manner.	2005 May	15888142
Differential antibiotic susceptibilities of starved Mycobacterium tuberculosis isolates.	2005 Nov	16251329
Complications related to dapsone use for Pneumocystis jirovecii pneumonia prophylaxis in solid organ transplant recipients.	2005 Nov	16212642
Childhood bullous pemphigoid successfully treated with diaminodiphenyl sulfone.	2005 Oct	16361732
Robust acoustic object detection.	2005 Oct	16266183
A case of drug-induced hypersensitivity syndrome with multiple organ involvement treated with plasma exchange.	2005 Oct	16202017
Renal hypersensitivity vasculitis associated with dapsone.	2005 Oct	16183407
The contribution of prosody to the perception of foreign accent.	2006	17293645
Acute methemoglobinemia following attempted suicide by Dapson.	2006 Apr	16513495
Anterior ischaemic optic neuropathy associated with Dapsone.	2006 Aug	16215545
[Disulone and hepatosiderosis].	2006 Aug-Sep	17053738
Guillain-Barré syndrome-like presentation in borderline leprosy with type-2 reaction.	2006 Feb 28	16638414
Role of human cyclooxygenase-2 in the bioactivation of dapsone and sulfamethoxazole.	2006 Jan	16214851
The Dapsone hypersensitivity syndrome revisited: a potentially fatal multisystem disorder with prominent hepatopulmonary manifestations.	2006 Jun 6	16756657
The sulfone syndrome secondary to dapsone prophylaxis in a patient undergoing unrelated hematopoietic stem cell transplantation.	2006 Sep	16639690
Neuroprotective effect of dapsone in patients with acute ischemic stroke: a pilot study.	2007 Apr	17509235
Consultative meeting to develop a strategy for treatment of cutaneous leishmaniasis. Institute Pasteur, Paris. 13-15 June, 2006.	2007 Apr 24	17456237
[Long-term follow-up of ofloxacin-combined therapy for leprosy patients].	2007 Sep	17877033
High risk of severe anaemia after chlorproguanil-dapsone+artesunate antimalarial treatment in patients with G6PD (A-) deficiency.	2008	19112496
Dapsone induces oxidative stress and impairs antioxidant defenses in rat liver.	2008 Aug 1	18602405
Complete atrioventricular block associated with dapsone therapy: a rare complication of dapsone-induced hypersensitivity syndrome.	2009 Aug	19583683
Synthesis and characterization of new optically active poly(azo-ester-imide)s via interfacial polycondensation.	2009 Mar	18563518

Patents

Sample Use Guides

In Vivo Use Guide

Apply 5% gel to the acne affected areas twice a day (Aczone gel). In dermatitis herpetiformis, the starting oral dose is 50 mg and in leprosy, the dose is 100 mg/day (Dapsone oral formulation).

Route of Administration: Other

In Vitro Use Guide

With Staphylococcus aureus (both methicillin-susceptible S. aureus-MSSA and methicillinresistant S. aureus-MRSA), dapsone MIC50, MIC90 were 128 ug/mL and 256 ug/mL, respectively. For Staphylococcus epidermidis overall, dapsone MIC50, MIC90 were 128 ug/mL and 256 ug/mL, respectively. Overall results with Enterococcus faecalis, dapsone MIC50, MIC90 were 256 ug/mL and 512 ug/mL, respectively. With Streptococcus agalactiae, dapsone MIC50, MIC90 were reported overall to be 32 ug/mL and 256 ug/mL, respectively. For Streptococcus pyogenes, dapsone MIC50, MIC90 were 32 ug/mL and 512 ug/mL, respectively.

Name

Type

Language

DAPSONE

Official Name

English

DAPSONE [VANDF]

Common Name

English

ACZONE

Brand Name

English

DAPSONE [WHO-IP]

Common Name

English

NSC-6091

Code

English

DAPSONE [INN]

Common Name

English

SULFACETAMIDE SODIUM IMPURITY D [EP]

Common Name

English

4,4'-SULFONYLDIANILINE

Systematic Name

English

DAPSONE [USP MONOGRAPH]

Common Name

English

DAPSONE [HSDB]

Common Name

English

DAPSONE [EP MONOGRAPH]

Common Name

English

DAPSONE [MART.]

Common Name

English

NOVOPHONE

Common Name

English

DAPSONUM [WHO-IP LATIN]

Common Name

English

DAPSONE [EP]

Common Name

English

DAPSONE [IARC]

Common Name

English

J04BA02

Code

English

DIAPHENYLSULFONE [JAN]

Common Name

English

DIAPHENYLSULFONE

Common Name

English

BENZENAMINE, 4,4'-SULFONYLBIS-

Systematic Name

English

DAPSONE [ORANGE BOOK]

Common Name

English

DAPSONE [WHO-DD]

Common Name

English

DAPSONE [MI]

Common Name

English

DAPSONE [USP-RS]

Common Name

English

NSC-6091D

Code

English

DAPSONE [USAN]

Common Name

English

SERVIDAPSON

Common Name

English

Classification Tree Code System Code

NDF-RT

N0000008053