BITHIONOL

Details

Stereochemistry	ACHIRAL
Molecular Formula	C12H6Cl4O2S
Molecular Weight	356.052
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

OC1=C(SC2=C(O)C(Cl)=CC(Cl)=C2)C=C(Cl)C=C1Cl

InChI

InChIKey=JFIOVJDNOJYLKP-UHFFFAOYSA-N

InChI=1S/C12H6Cl4O2S/c13-5-1-7(15)11(17)9(3-5)19-10-4-6(14)2-8(16)12(10)18/h1-4,17-18H

HIDE SMILES / InChI

Description
Sources: http://onlinelibrary.wiley.com/doi/10.1002/3527600418.mb9718kske0009/pdf
Curator's Comment: description was created based on several sources, including https://www.drugbank.ca/drugs/DB04813 | https://goo.gl/7Qnwi7 | https://www.ncbi.nlm.nih.gov/pubmed/26961873 | https://www.ncbi.nlm.nih.gov/pubmed/5567745 | https://www.ncbi.nlm.nih.gov/pubmed/23990907

Bithionol is a synthetic sulfanediyl-bis-dichlorphenol), potent photosensitizer with the potential to cause serious skin disorders, formerly marketed as an active ingredient in various topical drug products. Bithionol has antibacterial and anthelmintic properties along with algaecide activity. Bithionol has been shown to be a potent inhibitor of soluble adenylyl cyclase (sAC, Adenylate cyclase type 10 ), an intracellular enzyme important in the catalysis of ATP to cAMP. Bithionol is the first known sAC inhibitor to act through the bicarbonate binding site via a mostly allosteric mechanism. Bithionol is used for treatment of tapeworm infections of dogs, cats, and poultry and for tapeworm and rumen fluke infections of sheep, horses, cattle, and goats.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Adenylate cyclase type 10 2 Target ID: CHEMBL5854 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26961873	Inhibitor 8297		4.0 µM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Intestinal capillariasis 2 Sources: https://www.ncbi.nlm.nih.gov/pubmed/5567745	Primary		Not Provided 504	Actamer Approved Use Unknown

Doses

Dose	Population	Adverse events
1 % 1 times / day single, topical Studied dose Dose: 1 %, 1 times / day Route: topical Route: single Dose: 1 %, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/13826897/	healthy, 22 years n = 1 Health Status: healthy Age Group: 22 years Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/13826897/	Other AEs: Contact dermatitis... Other AEs: Contact dermatitis Sources: https://pubmed.ncbi.nlm.nih.gov/13826897/
2.4 g 1 times / day multiple, oral Studied dose Dose: 2.4 g, 1 times / day Route: oral Route: multiple Dose: 2.4 g, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/5567745/	unhealthy, mean age 35 years n = 8 Health Status: unhealthy Condition: intestinal capillariasis Age Group: mean age 35 years Sex: M+F Population Size: 8 Sources: https://pubmed.ncbi.nlm.nih.gov/5567745/	Other AEs: Abdominal pain aggravated... Other AEs: Abdominal pain aggravated (37.5%) Sources: https://pubmed.ncbi.nlm.nih.gov/5567745/

AEs

AE	Significance	Dose	Population
Contact dermatitis		1 % 1 times / day single, topical Studied dose Dose: 1 %, 1 times / day Route: topical Route: single Dose: 1 %, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/13826897/	healthy, 22 years n = 1 Health Status: healthy Age Group: 22 years Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/13826897/
Abdominal pain aggravated	37.5%	2.4 g 1 times / day multiple, oral Studied dose Dose: 2.4 g, 1 times / day Route: oral Route: multiple Dose: 2.4 g, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/5567745/	unhealthy, mean age 35 years n = 8 Health Status: unhealthy Condition: intestinal capillariasis Age Group: mean age 35 years Sex: M+F Population Size: 8 Sources: https://pubmed.ncbi.nlm.nih.gov/5567745/

Sourcing

Vendor/Aggregator	ID	URL
3B Scientific (Wuhan) Corp	3B3-046256	http://www.3bsc.com/index/pro_info.php?id=82855
AHH Chemical co.,ltd	MT-30989	http://www.ahhchemical.com/product/MT-30989.html
Ambeed	A289469	https://www.ambeed.com/products/6385-58-6.html
Ambinter	Amb10843662	http://www.ambinter.com/reference/10843662
Angel Pharmatech	AG260602	http://www.angelpharmatech.com/6385-58-6.html
Aurora Fine Chemicals LLC	A17.909.556	http://online.aurorafinechemicals.com/info?ID=A17.909.556
BLD Pharm	BD64694	http://www.bldpharm.com/products/6385-58-6.html
BOC Sciences	6385-58-6	https://www.bocsci.com/2-2-thiobis-4-6-dichlorophenol-disodium-salt-cas-6385-58-6-item-30849.html
Chemspace	CSSB00102585214	https://chem-space.com/CSSB00102585214
Combi-Blocks	QE-0841	http://www.combi-blocks.com/cgi-bin/find.cgi?QE-0841
Finetech	FT-0708482	http://www.finetechnology-ind.com/prod/detail/pub/6385-58-6.html
Sigma-Aldrich	CDS000488_ALDRICH	https://www.sigmaaldrich.com/catalog/product/aldrich/cds000488?utm_source=pubchem&utm_campaign=pubchem_2017&utm_medium=referral
TCI (Tokyo Chemical Industry)	T0406	http://www.tcichemicals.com/eshop/en/us/commodity/T0406/index.html
abcr GmbH	AB142463	http://www.abcr.de/shop/en/AB142463
eNovation Chemicals	D108017	https://www.enovationchem.com/ProductDetails.asp?ProductID=D108017

PubMed

Title	Date	PubMed
Treatment of experimental pneumocystosis: review of 7 years of experience and development of a new system for classifying antimicrobial drugs.	1992 Sep	1416885
Efficacy of 101 antimicrobials and other agents on the development of Cryptosporidium parvum in vitro.	1996 Dec	9039272
Paragonimiasis in Yongjia County, Zhejiang Province, China: clinical, parasitological and karyotypic studies on Paragonimus westermani.	2001 Dec	12041551
[Antiparasitic treatments in pregnant women and in children in 2003].	2003	14763305
[Fascioliasis: diagnosis, epidemiology and treatment].	2003 Apr-Jun	15127652
Sonographic findings of hepatic lesions in human fascioliasis.	2003 Sep	12923880
A native 13-kDa fatty acid binding protein from the liver fluke Fasciola hepatica.	2004 Sep 24	15374624
Contractile activity and motility responses of the dog heartworm Dirofilaria immitis to classical anthelmintics and other compounds.	2005 Nov 25	16076531
Kinetic, inhibition and structural studies on 3-oxoacyl-ACP reductase from Plasmodium falciparum, a key enzyme in fatty acid biosynthesis.	2006 Jan 15	16225460
Induction of keratinocyte apoptosis by photosensitizing chemicals plus UVA.	2007 Feb	17141480
Slack and Slick K(Na) channels regulate the accuracy of timing of auditory neurons.	2007 Mar 7	17344399
Novel inhibitors complexed with glutamate dehydrogenase: allosteric regulation by control of protein dynamics.	2009 Aug 21	19531491
Prediction of pharmacological and xenobiotic responses to drugs based on time course gene expression profiles.	2009 Dec 2	19956587
Combining chemical genomics screens in yeast to reveal spectrum of effects of chemical inhibition of sphingolipid biosynthesis.	2009 Jan 14	19144191
Drug discovery for schistosomiasis: hit and lead compounds identified in a library of known drugs by medium-throughput phenotypic screening.	2009 Jul 14	19597541
[Phosphatases of cestodes Bothriocephalus scorpii and influence of some anthelmintic preparations on activities of these enzymes].	2009 Mar-Apr	19505013
Further development of bithionol therapy as a treatment for amoebic gill disease in Atlantic salmon, Salmo salar L.	2009 May	19243491
Endoscopic management of biliary fascioliasis: a case report.	2010 Mar 6	20205932
Identification of known drugs that act as inhibitors of NF-kappaB signaling and their mechanism of action.	2010 May 1	20067776
Profiling of a prescription drug library for potential renal drug-drug interactions mediated by the organic cation transporter 2.	2011 Jul 14	21599003

Patents

Sample Use Guides

In Vivo Use Guide

After oral administration of single bithionol doses of 30 mg/kg body weight to healthy test persons (fasting, number not stated) no effects were observed, single oral doses of 50 mg/kg body weight caused diarrhoea and 150 mg/kg body weight prolonged diarrhoea, nausea and abdominal pains

Route of Administration: Oral

In Vitro Use Guide

Cytotoxic effect of BT (Bithionol) was evaluated against a panel of ovarian cancer cell lines (A2780 & A2780-CDDP OVACAR-3, SKOV-3, IGROV-1, and IGROV-1CDDP). A 20 mM stock of BT was prepared in DMSO and all the working dilutions were prepared in DMEM media. Ovarian cancer cell lines (5 × 103 cells/well) were plated into 96-well flat bottom plates (Corning, Inc., Corning, NY) and incubated for overnight. Cells were treated with different concentrations of BT ranging from 0.178 μM to 400 μM and further incubated for 48 hrs or 72 hrs. At least 4–6 hrs before the end of treatment time, presto blue reagent was added and incubated for total of 48 or 72 hrs and fluorescence measured (540 nm excitation/590 nm emissions). DMSO concentration was corrected to 1% in all wells.

Name

Type

Language

BITHIONOL

Official Name

English

Bithionol [WHO-DD]

Common Name

English

bithionol [INN]

Common Name

English

BITHIN

Brand Name

English

BITHIONOL [HSDB]

Common Name

English

BITHIONOL [MART.]

Common Name

English

NSC-47129

Code

English

BITHIONOL [MI]

Common Name

English

LOROTHIDOL

Brand Name

English

BITHIONOL [JAN]

Common Name

English

2,2'-THIOBIS(4,6-DICHLOROPHENOL)

Systematic Name

English

Classification Tree Code System Code

WHO-ATC

P02BX01