DANTHRON

US Previously Marketed

Details

Stereochemistry	ACHIRAL
Molecular Formula	C14H8O4
Molecular Weight	240.2109
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

OC1=CC=CC2=C1C(=O)C3=C(O)C=CC=C3C2=O

InChI

InChIKey=QBPFLULOKWLNNW-UHFFFAOYSA-N

InChI=1S/C14H8O4/c15-9-5-1-3-7-11(9)14(18)12-8(13(7)17)4-2-6-10(12)16/h1-6,15-16H

HIDE SMILES / InChI

Description
Sources: http://www.sciencedirect.com/science/article/pii/B9780123864543012148
Curator's Comment: Description was created based on several sources, including https://ntp.niehs.nih.gov/ntp/roc/content/profiles/danthron.pdf

Danthron, a natural product, was originally extracted from the roots and rhizome of Polygonaceae plant. Danthron is an anthraquinone. Danthron has been widely administrated as a laxative since the 1900s. In the United States, danthron has been forbidden to continual use as laxative because it is considered to be a carcinogen. In the UK, it is not marketed alone but in combination with poloxamer 188 as co-danthramer and with docusate as co-danthrusate; in the UK, its use is strictly restricted to the elderly and to the terminally ill of all ages because of concerns about carcinogenicity and hepatotoxicity. It has only a limited role in the treatment of constipation.

Approval Year

Targets

Primary Target	Pharmacology	Potency
AMP-activated protein kinase, AMPK 17 Target ID: CHEMBL2096907 Sources: http://www.nature.com/aps/journal/v34/n8/pdf/aps201339a.pdf	Activator 1430
DNA topoisomerase II alpha 37 Target ID: CHEMBL3586 Sources: http://www.ncbi.nlm.nih.gov/pubmed/?term=9630566	Inhibitor 8297	14.0 µM [IC50]
Retinoid X receptor alpha 11 Target ID: CHEMBL2061 Sources: http://www.jbc.org/content/286/3/1868.full.pdf+html	Antagonist 2778	7.5 µM [Kd]
Apoptosis 155 Target ID: map04210 Sources: http://www.ncbi.nlm.nih.gov/pubmed/19784869	Activator 1430

Conditions

Condition	Modality	Targets	Highest Phase	Product
Constipation in terminally ill patients 1 Sources: http://www.drugs.com/uk/pdf/leaflet/676118.pdf	Curative		Withdrawn	Normax Approved Use Normax 50mg/60mg Capsules should only be used to relieve constipation in patients who are seriously ill. Normax 50mg/60mg Capsules work by encouraging normal bowel movements.

Doses

Dose	Population	Adverse events
25 mg 1 times / day multiple, oral Recommended Dose: 25 mg, 1 times / day Route: oral Route: multiple Dose: 25 mg, 1 times / day Co-administed with:: poloxalkol(200 mg; oral; 1/day) Sources: https://pubmed.ncbi.nlm.nih.gov/2594597/	unhealthy, 18 years n = 1 Health Status: unhealthy Condition: constipation Age Group: 18 years Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/2594597/	Other AEs: Leiomyosarcoma... Other AEs: Leiomyosarcoma Sources: https://pubmed.ncbi.nlm.nih.gov/2594597/
25 mg 1 times / day single, oral Studied dose Dose: 25 mg, 1 times / day Route: oral Route: single Dose: 25 mg, 1 times / day Co-administed with:: poloxalkol(200 mg; oral; 1/day) Sources: https://pubmed.ncbi.nlm.nih.gov/638688/	unhealthy, 51 years n = 1 Health Status: unhealthy Condition: psychiatric ailments Age Group: 51 years Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/638688/	Other AEs: Skin discoloration... Other AEs: Skin discoloration Sources: https://pubmed.ncbi.nlm.nih.gov/638688/
25 mg 1 times / day multiple, oral Recommended Dose: 25 mg, 1 times / day Route: oral Route: multiple Dose: 25 mg, 1 times / day Co-administed with:: poloxalkol(200 mg; oral; 1/day) Sources: https://pubmed.ncbi.nlm.nih.gov/5371464/	unhealthy, 65 to 88 years n = 20 Health Status: unhealthy Condition: constipation Age Group: 65 to 88 years Sex: M+F Population Size: 20 Sources: https://pubmed.ncbi.nlm.nih.gov/5371464/	Other AEs: Diarrhoea, Faecal incontinence... Other AEs: Diarrhoea (35%) Faecal incontinence (55%) Rash (15%) Sources: https://pubmed.ncbi.nlm.nih.gov/5371464/
50 mg 1 times / day multiple, oral Recommended Dose: 50 mg, 1 times / day Route: oral Route: multiple Dose: 50 mg, 1 times / day Co-administed with:: docusate sodium(60 mg; oral; 1/day) Sources: https://pubmed.ncbi.nlm.nih.gov/1451505/	unhealthy, 80 and 69 years n = 2 Health Status: unhealthy Condition: constipation Age Group: 80 and 69 years Sex: F Population Size: 2 Sources: https://pubmed.ncbi.nlm.nih.gov/1451505/	Disc. AE: Contact dermatitis... AEs leading to discontinuation/dose reduction: Contact dermatitis Sources: https://pubmed.ncbi.nlm.nih.gov/1451505/

AEs

AE	Significance	Dose	Population
Leiomyosarcoma		25 mg 1 times / day multiple, oral Recommended Dose: 25 mg, 1 times / day Route: oral Route: multiple Dose: 25 mg, 1 times / day Co-administed with:: poloxalkol(200 mg; oral; 1/day) Sources: https://pubmed.ncbi.nlm.nih.gov/2594597/	unhealthy, 18 years n = 1 Health Status: unhealthy Condition: constipation Age Group: 18 years Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/2594597/
Skin discoloration		25 mg 1 times / day single, oral Studied dose Dose: 25 mg, 1 times / day Route: oral Route: single Dose: 25 mg, 1 times / day Co-administed with:: poloxalkol(200 mg; oral; 1/day) Sources: https://pubmed.ncbi.nlm.nih.gov/638688/	unhealthy, 51 years n = 1 Health Status: unhealthy Condition: psychiatric ailments Age Group: 51 years Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/638688/
Rash	15%	25 mg 1 times / day multiple, oral Recommended Dose: 25 mg, 1 times / day Route: oral Route: multiple Dose: 25 mg, 1 times / day Co-administed with:: poloxalkol(200 mg; oral; 1/day) Sources: https://pubmed.ncbi.nlm.nih.gov/5371464/	unhealthy, 65 to 88 years n = 20 Health Status: unhealthy Condition: constipation Age Group: 65 to 88 years Sex: M+F Population Size: 20 Sources: https://pubmed.ncbi.nlm.nih.gov/5371464/
Diarrhoea	35%	25 mg 1 times / day multiple, oral Recommended Dose: 25 mg, 1 times / day Route: oral Route: multiple Dose: 25 mg, 1 times / day Co-administed with:: poloxalkol(200 mg; oral; 1/day) Sources: https://pubmed.ncbi.nlm.nih.gov/5371464/	unhealthy, 65 to 88 years n = 20 Health Status: unhealthy Condition: constipation Age Group: 65 to 88 years Sex: M+F Population Size: 20 Sources: https://pubmed.ncbi.nlm.nih.gov/5371464/
Faecal incontinence	55%	25 mg 1 times / day multiple, oral Recommended Dose: 25 mg, 1 times / day Route: oral Route: multiple Dose: 25 mg, 1 times / day Co-administed with:: poloxalkol(200 mg; oral; 1/day) Sources: https://pubmed.ncbi.nlm.nih.gov/5371464/	unhealthy, 65 to 88 years n = 20 Health Status: unhealthy Condition: constipation Age Group: 65 to 88 years Sex: M+F Population Size: 20 Sources: https://pubmed.ncbi.nlm.nih.gov/5371464/
Contact dermatitis	Disc. AE	50 mg 1 times / day multiple, oral Recommended Dose: 50 mg, 1 times / day Route: oral Route: multiple Dose: 50 mg, 1 times / day Co-administed with:: docusate sodium(60 mg; oral; 1/day) Sources: https://pubmed.ncbi.nlm.nih.gov/1451505/	unhealthy, 80 and 69 years n = 2 Health Status: unhealthy Condition: constipation Age Group: 80 and 69 years Sex: F Population Size: 2 Sources: https://pubmed.ncbi.nlm.nih.gov/1451505/

Overview

CYP3A4	CYP2C9	CYP2D6	hERG

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
P-gp 1461	UGT1A1 418 UGT1A6 307 UGT1A7 236 UGT1A9 380 UGT1A10 291

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
P-gp 1650	inhibitor 3277 Sources: https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1747-0285.2011.01089.x	no

Drug as victim

Target	Modality	Activity
UGT1A1 418	substrate 3367 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwxMjg3NjE3IiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDUzNDE4In19, https://www.annualreviews.org/doi/10.1146/annurev.pharmtox.40.1.581	no
UGT1A6 307	substrate 3367 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwxNzQzMzE2IiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDUzNDE4In19, https://www.annualreviews.org/doi/10.1146/annurev.pharmtox.40.1.581	no
UGT1A9 380	substrate 3367 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwxNzQzMzE5IiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDUzNDE4In19, https://www.annualreviews.org/doi/10.1146/annurev.pharmtox.40.1.581	no
UGT1A10 291	substrate 3367 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwxNzQzMzIwIiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDUzNDE4In19, https://www.annualreviews.org/doi/10.1146/annurev.pharmtox.40.1.581	yes
UGT1A7 236	substrate 3367 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwxNzQzMzE3IiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDUzNDE4In19, https://www.annualreviews.org/doi/10.1146/annurev.pharmtox.40.1.581	yes

Sourcing

Vendor/Aggregator	ID	URL
001 Chemical	DY455324	https://www.001chemical.com/chem/117-10-2
3B Scientific (Wuhan) Corp	3B1-00529	http://www.3bsc.com/index/pro_info.php?id=20741
AA Blocks	AA000DF4	https://www.aablocks.com/goods/Goods/detail?id=AA000DF4
AEchem Scientific Corp., USA	AE038910	http://www.aechemsc.com/info_products/AE038910.php
AHH Chemical co.,ltd	NP-0345	http://www.ahhchemical.com/product/NP-0345.html
AK Scientific, Inc. (AKSCI)	R229	http://www.aksci.com/item_detail.php?cat=R229
Aaron Chemicals	AR000E6W	http://www.aaronchem.com/117-10-2
AbMole Bioscience	M5549	http://www.abmole.com/products/danthron.html
Acadechem	ACDS-033112	http://www.acadechemical.com/product/107811
Accela ChemBio Inc	SY011288	http://www.accelachem.com/cn/search.html?keyword=SY011288&attname=GoodsCode
Achemica	ACMC-20mzuc	http://www.achemica.com/prodinfo/?id=227325
Achemo Scientific Limited	AC-23294	http://www.achemo.com/search/?Keyword=117-10-2
Acorn PharmaTech	ACN-035237	http://www.acornpharmatech.com/
Acros Organics	AC114830050	https://www.fishersci.com/shop/products/1-8-dihydroxyanthraquinone-90-95-acros-organics/AC114830050
Acros Organics	AC114831000	https://www.fishersci.com/shop/products/1-8-dihydroxyanthraquinone-90-95-acros-organics/AC114831000
Acros Organics	AC114835000	https://www.fishersci.com/shop/products/1-8-dihydroxyanthraquinone-90-95-acros-organics/AC114835000
Alfa Aesar	A12001	https://www.alfa.com/en/catalog/A12001/
Alfa Chemistry	AP117102	https://reagents.alfa-chemistry.com/product/danthrone-cas-117-10-2-2185.html
Alichem	19150111	http://www.alichem.com/en/products/117-10-2.html
Ambinter	Amb1349101	http://www.ambinter.com/reference/1349101
Angene	AGN-PC-0JK6EB	http://www.angenechemical.com/productshow/AGN-PC-0JK6EB.html
Anward	ANW-17004	http://www.anward.com/pro_result/3917
Ark Pharm	AK208660	http://www.arkpharminc.com/products/117-10-2.html
Ark Pharma Scientific Limited	N-1556	http://www.arkpharmtech.com/product/241897.html
Aronis	ARONIS23892	http://www.aronis.ru/store/index.php?main_page=product_info&cPath=1&products_id=1164
AvaChem Scientific	4000	http://www.avachem.com/productSearch.asp?4000
BLD Pharm	BD55176	http://www.bldpharm.com/products/117-10-2.html
BOC Sciences	1246816-27-2	https://isotope.bocsci.com/product/1-8-dihydroxyanthraquinone-d6-cas-1246816-27-2-346722.html
BioChemPartner	BCP31079	http://www.biochempartner.com/117-10-2-BCP31079
BioCrick	BCN6048	http://www.biocrick.com/Dantron-BCN6048.html
BioSynth	W-108572	https://www.biosynth.com/en/products/chemical-intermediates/advanced-intermediates/products/W-108572.html
CSNpharm	CSN17102	https://www.csnpharm.com/products/1,8-dihydroxyanthraquinone.html
Chem Scene	CS-4392	http://www.chemscene.com/117-10-2.html
ChemFaces	CFN99271	http://www.chemfaces.com/natural/Dantron-CFN99271.html
ChemMol	49426487	http://www.chemmol.com/chemmol/49426487.html
ChemMol	80101169	http://www.chemmol.com/chemmol/80101169.html
Chemspace	CSSB00016997201	https://chem-space.com/CSSB00016997201
Clearsynth	CS-T-89385	https://www.clearsynth.com/en/CST89385.html
DC Chemicals	DCE-005	http://www.dcchemicals.com//product_show-1_8_Dihydroxyanthraquinone.html
Finetech	FT-0624445	http://www.finetechnology-ind.com/prod/detail/pub/117-10-2.html
FondChemical	FDB-2803	http://www.fondchemical.com/cpshow_cid_8_pid_2090.html
Glentham Life Sciences	GK4516	http://www.glentham.com/products/product/GK4516/
Hairui	HR135029	http://www.hairuichem.com/en/product/117-10-2.html
LGC Standards	DRE-C11961000	https://www.lgcstandards.com/US/en/p/DRE-C11961000
LGC Standards	LGCFOR0137.01	https://www.lgcstandards.com/US/en/p/LGCFOR0137.01
LGC Standards	MM0137.01	https://www.lgcstandards.com/US/en/p/MM0137.01
Lab Network	LN00159216	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN00159216
Matrix Scientific	58300	https://www.matrixscientific.com/058300.html
MedChem Express	HY-B0923	https://www.medchemexpress.com/Danthron.html
Molcore	MC455324	https://www.molcore.com/product/117-10-2
MuseChem	I000607	https://www.musechem.com/product/I000607.html
Parchem	1364	http://www.parchem.com/chemical-supplier-distributor/1-8-Dihydroxy-Anthraquinone-002712.aspx
R&D Chemicals	417	http://www.rdchemicals.com/chemicals.php?mode=details&mol_id=7720
Renno Tech	RP28420	http://www.rennotech.com/product_show.asp?id=34036
Sigma-Aldrich	D108103_ALDRICH	https://www.sigmaaldrich.com/catalog/product/aldrich/d108103?utm_source=pubchem&utm_campaign=pubchem_2017&utm_medium=referral
Sigma-Aldrich	V900576_VETEC	https://www.sigmaaldrich.com/catalog/product/vetec/v900576?utm_source=pubchem&utm_campaign=pubchem_2017&utm_medium=referral
Sinfoo Biotech	S017455	http://www.sinfoobiotech.com/product/1020853
Smolecule	S525002	http://www.smolecule.com/products/s525002
Smolecule	S748642	https://www.smolecule.com/products/s748642
TCI (Tokyo Chemical Industry)	D0563	http://www.tcichemicals.com/eshop/en/us/commodity/D0563/index.html
THE BioTek	bt-264432	https://www.thebiotek.com/product/inhibitors/bt-264432
VladaChem	VL266649-100G	https://www.vladachem.com/product.php?products=117-10-2
abcr GmbH	AB109119	http://www.abcr.com/shop/en/AB109119
eNovation Chemicals	D409459	http://www.enovationchem.com/productDetails.asp?productID=D409459
iChemical	EBD217295	http://www.ichemical.com/products/117-10-2.html?utm_source=PubChem&utm_medium=website&utm_campaign=product%20catalogs
mcule	MCULE-5800615690	https://mcule.com/MCULE-5800615690/

PubMed

Title	Date	PubMed
Screening for new compounds with antiherpes activity.	1984 Oct	6517562
Differential inhibition of HIV-1 preintegration complexes and purified integrase protein by small molecules.	1996 Sep 3	8790401
Antimutagenic effects of black tea (World Blend) and its two active polyphenols theaflavins and thearubigins in Salmonella assays.	2002 Nov	12410547
1,8-Dihydroxyanthraquinone anchored on silica gel: synthesis and application as solid phase extractant for lead(II), zinc(II) and cadmium(II) prior to their determination by flame atomic absorption spectrometry.	2002 Oct 16	18968796
Bryoanthrathiophene, a new antiangiogenic constituent from the bryozoan Watersipora subtorquata (d'Orbigny, 1852).	2002 Sep	12350162
Inhibition of MAO A and B by some plant-derived alkaloids, phenols and anthraquinones.	2004 Apr	15120460
Growth responses of Cassia obtusifolia toward human intestinal bacteria.	2004 Jul	15261390
Danthron inhibits the neurotoxicity induced by various compounds causing oxidative damages including beta-amyloid (25-35) in primary cortical cultures.	2004 May	15133254
Interaction of anthracene and its oxidative derivatives with human serum albumin.	2006	16404478
Laxatives for the management of constipation in palliative care patients.	2006 Oct 18	17054172
Defensive components in insect eggs: are anthraquinones produced during egg development?	2006 Sep	16835809
Study of interactions of anthraquinones with DNA using ethidium bromide as a fluorescence probe.	2008 Jun	17825605
Voltammetric Behavior of o-Nitrophenol and Damage to DNA.	2008 Mar	19325751
Is senna laxative use associated to cathartic colon, genotoxicity, or carcinogenicity?	2009	20107583
1,8-Bis(tos-yloxy)-9,10-anthraquinone.	2009 Dec 4	21580139
Structure-activity relationships of anthraquinones on the suppression of DNA-binding activity of the aryl hydrocarbon receptor induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin.	2009 Mar	19269596
Anthraquinones danthron and quinizarin exert antiproliferative and antimetastatic activity on murine B16-F10 melanoma cells.	2010 Feb	20332452
Danthron induces DNA damage and inhibits DNA repair gene expressions in GBM 8401 human brain glioblastoma multiforms cells.	2010 Jul	20369292
Comparative developmental toxicity of environmentally relevant oxygenated PAHs.	2013 Sep 1	23684558

Patents

Sample Use Guides

In Vivo Use Guide

The usual dose for adults is one to three capsules at bedtime. The usual dose for children aged 6-12 years is one capsule at bedtime. Normax 50mg/60mg Capsules are not recommended for use by children under 6 years of age. This product should be taken orally (by mouth). You must swallow the capsules whole with a drink of water. The capsules must not be crushed or chewed. Normax 50mg/60mg Capsules normally begin to work 8 hours after the dose is taken.

Route of Administration: Oral

In Vitro Use Guide

10 uM danthron reduces growth of B16-F10 melanoma by 83%

Name

Type

Language

DANTHRON

Common Name

English

1,8-DIHYDROXYANTHRACENE-9,10-DIONE

Systematic Name

English

CHRYSAZIN

Common Name

English

DITHRANOL IMPURITY B [EP IMPURITY]

Common Name

English

NSC-38626

Code

English

DANTHRON [MI]

Common Name

English

Dantron [WHO-DD]

Common Name

English

DANTRON [MART.]

Common Name

English

NSC-646568

Code

English

DORBANE

Brand Name

English

dantron [INN]

Common Name

English

DANTHRON [HSDB]

Common Name

English

1,8-Dihydroxyanthraquinone

Systematic Name

English

DANTRON

Official Name

English

DANTRON [IARC]

Common Name

English

ISTIZIN

Brand Name

English

PILULES VINCHY N.F.

Brand Name

English

DANTHRON [VANDF]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C45177