Bithionol | Lorothidol | CP-3438 | CAS#97-18-7 | ENPP2 Protein Inhibitor

MedKoo Cat#: 329217 | Name: Bithionol

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Description:

WARNING: This product is for research use only, not for human or veterinary use.

Bithionol, also known as Lorothidol and CP-3438, is an ENPP2 protein inhibitor used to treat hepatic fascioliasis. Bithionol is a clinically approved anti-parasitic drug used as an anti-ovarian cancer drug. Bithionol exhibits cytotoxic effects on various ovarian cancer cell lines regardless of their sensitivities to cisplatin. Cell death appears to be via caspases mediated apoptosis. The mechanisms of action appear to be partly via cell cycle arrest, reactive oxygen species generation and inhibition of autotaxin.

Chemical Structure

Bithionol

CAS#97-18-7

Theoretical Analysis

MedKoo Cat#: 329217

Name: Bithionol

CAS#: 97-18-7

Chemical Formula: C12H6Cl4O2S

Exact Mass: 353.8843

Molecular Weight: 356.04

Elemental Analysis: C, 40.48; H, 1.70; Cl, 39.83; O, 8.99; S, 9.00

Price and Availability

Size	Price	Availability	Quantity
25g	USD 350.00	2 Weeks
50g	USD 550.00	2 Weeks

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Related CAS #

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Synonym

Bithionol; Bitin; CP 3438; CP-3438; CP3438; Lorothidol; NSC 47129; NSC-47129; NSC47129; NSC9872; NSC 9872; NSC-9872

IUPAC/Chemical Name

6,6'-thiobis(2,4-dichlorophenol)

InChi Key

JFIOVJDNOJYLKP-UHFFFAOYSA-N

InChi Code

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

SMILES Code

ClC1=CC(Cl)=C(O)C(SC2=CC(Cl)=CC(Cl)=C2O)=C1

Appearance

Solid powder

Purity

>98% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

Soluble in DMSO

Shelf Life

>2 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.9001

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Product Data

Product Data

Instruction

View handling instruction

Biological target:

Bithionol is a clinically approved anti-parasitic drug; has been shown to inhibit solid tumor growth in several preclinical cancer models.

In vitro activity:

Bithionol was able to reduce diphtheria, cholera, and Pseudomonas toxins-mediated cytotoxicities with an EC50 of 10 μM (Fig. 4d–f). This study tested the effect of different concentrations of Bithionol for the ability to inhibit the proteolytic cleavage of substrates specific for cellular caspases-3, 6, and 3/7. This study observed a linear dose-dependent caspase-inhibitory efficacy of Bithionol, with an IC50 of 21, 13, and 11 μM for caspases-3, -6, and -3/7, respectively (Fig. 4g). These results are consistent with anti-toxins EC50’s of Bithionol in cellular tests (Fig. 4d–f). Reference: Sci Rep. 2016; 6: 34475. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5043268/

In vivo activity:

To investigate whether pharmaceutical grade BT (bithionol) can inhibit the growth of implanted human EOC xenografts in a nude mice model, animals were inoculated with SKOV3-luc-D3 cells via the IP route as described in Materials and Methods. Representative bioluminescent images (dorsal views) of control and BT-treated mice are shown in Figure 1. Reference: Anticancer Drugs. 2016 Jul; 27(6): 547–559. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5053334/

	Solvent	mg/mL	mM	comments
Solubility
	DMSO	41.3	116.08

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 356.04 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

1. Leonardi W, Zilbermintz L, Cheng LW, Zozaya J, Tran SH, Elliott JH, Polukhina K, Manasherob R, Li A, Chi X, Gharaibeh D, Kenny T, Zamani R, Soloveva V, Haddow AD, Nasar F, Bavari S, Bassik MC, Cohen SN, Levitin A, Martchenko M. Bithionol blocks pathogenicity of bacterial toxins, ricin, and Zika virus. Sci Rep. 2016 Sep 30;6:34475. doi: 10.1038/srep34475. PMID: 27686742; PMCID: PMC5043268. 2. Ayyagari VN, Brard L. Bithionol inhibits ovarian cancer cell growth in vitro - studies on mechanism(s) of action. BMC Cancer. 2014 Feb 4;14:61. doi: 10.1186/1471-2407-14-61. PMID: 24495391; PMCID: PMC3922745.

In vitro protocol:

In vivo protocol:

1. Ayyagari VN, Johnston NA, Brard L. Assessment of the antitumor potential of Bithionol in vivo using a xenograft model of ovarian cancer. Anticancer Drugs. 2016 Jul;27(6):547-59. doi: 10.1097/CAD.0000000000000364. PMID: 27058706; PMCID: PMC5053334.

1: Florent RL, Becker JA, Powell MD. In vitro toxicity of bithionol and bithionol sulphoxide to Neoparamoeba spp., the causative agent of amoebic gill disease (AGD). Dis Aquat Organ. 2010 Sep 17;91(3):257-62. doi: 10.3354/dao02269. PubMed PMID: 21133325. 2: Florent RL, Becker J, Powell MD. Further development of bithionol therapy as a treatment for amoebic gill disease in Atlantic salmon, Salmo salar L. J Fish Dis. 2009 May;32(5):391-400. doi: 10.1111/j.1365-2761.2008.01001.x. PubMed PMID: 19243491. 3: Ayyagari VN, Brard L. Bithionol inhibits ovarian cancer cell growth in vitro - studies on mechanism(s) of action. BMC Cancer. 2014 Feb 4;14:61. doi: 10.1186/1471-2407-14-61. PubMed PMID: 24495391; PubMed Central PMCID: PMC3922745. 4: Sanada Y, Senba H, Mochizuki R, Arakaki H, Gotoh T, Fukumoto S, Nagahata H. Evaluation of marked rise in fecal egg output after bithionol administration to horse and its application as a diagnostic marker for equine Anoplocephala perfoliata infection. J Vet Med Sci. 2009 May;71(5):617-20. PubMed PMID: 19498288. 5: Reid L, Khammo N, Clothier RH. An evaluation of the effects of photoactivation of bithionol, amiodarone and chlorpromazine on human keratinocytes in vitro. Altern Lab Anim. 2007 Oct;35(5):471-85. PubMed PMID: 18001169. 6: Florent RL, Becker JA, Powell MD. Evaluation of bithionol as a bath treatment for amoebic gill disease caused by Neoparamoeba spp. Vet Parasitol. 2007 Mar 31;144(3-4):197-207. PubMed PMID: 17129675. 7: Matsubara K, Sanoh S, Ohta S, Kitamura S, Sugihara K, Fujimoto N. An improved thyroid hormone reporter assay to determine the thyroid hormone-like activity of amiodarone, bithionol, closantel and rafoxanide. Toxicol Lett. 2012 Jan 5;208(1):30-5. doi: 10.1016/j.toxlet.2011.10.004. PubMed PMID: 22015988. 8: Sakamoto M, Takeba K, Sasamoto T, Kusano T, Hayashi H, Kanai S, Kanda M, Nagayama T. Determination of bithionol, bromophen, nitroxynil, oxyclozanide, and tribromsalan in milk with liquid chromatography coupled with tandem mass spectrometry. J AOAC Int. 2010 Jul-Aug;93(4):1340-6. PubMed PMID: 20922970. 9: Kleinboelting S, Ramos-Espiritu L, Buck H, Colis L, van den Heuvel J, Glickman JF, Levin LR, Buck J, Steegborn C. Bithionol Potently Inhibits Human Soluble Adenylyl Cyclase through Binding to the Allosteric Activator Site. J Biol Chem. 2016 Apr 29;291(18):9776-84. doi: 10.1074/jbc.M115.708255. PubMed PMID: 26961873; PubMed Central PMCID: PMC4850313. 10: Reid L, Clothier RH, Khammo N. Hydrogen peroxide induced stress in human keratinocytes and its effect on bithionol toxicity. Toxicol In Vitro. 2001 Aug-Oct;15(4-5):441-5. PubMed PMID: 11566576. 11: Leonardi W, Zilbermintz L, Cheng LW, Zozaya J, Tran SH, Elliott JH, Polukhina K, Manasherob R, Li A, Chi X, Gharaibeh D, Kenny T, Zamani R, Soloveva V, Haddow AD, Nasar F, Bavari S, Bassik MC, Cohen SN, Levitin A, Martchenko M. Bithionol blocks pathogenicity of bacterial toxins, ricin, and Zika virus. Sci Rep. 2016 Sep 30;6:34475. doi: 10.1038/srep34475. PubMed PMID: 27686742; PubMed Central PMCID: PMC5043268. 12: Ayyagari VN, Johnston NA, Brard L. Assessment of the antitumor potential of Bithionol in vivo using a xenograft model of ovarian cancer. Anticancer Drugs. 2016 Jul;27(6):547-59. doi: 10.1097/CAD.0000000000000364. PubMed PMID: 27058706; PubMed Central PMCID: PMC5053334. 13: Eleuteri S, Di Giovanni S, Rockenstein E, Mante M, Adame A, Trejo M, Wrasidlo W, Wu F, Fraering PC, Masliah E, Lashuel HA. Novel therapeutic strategy for neurodegeneration by blocking Aβ seeding mediated aggregation in models of Alzheimer's disease. Neurobiol Dis. 2015 Feb;74:144-57. doi: 10.1016/j.nbd.2014.08.017. PubMed PMID: 25173807; PubMed Central PMCID: PMC4323687. 14: Kodama K. [Human fascioliasis: comparison of a fasciolicidal effect of bithionol and praziquantel]. Kansenshogaku Zasshi. 1997 Nov;71(11):1162-7. Review. Japanese. PubMed PMID: 9455057. 15: Hozumi H, Hokari R, Kurihara C, Narimatsu K, Sato H, Sato S, Ueda T, Higashiyama M, Okada Y, Watanabe C, Komoto S, Tomita K, Kawaguchi A, Nagao S, Miura S. Involvement of autotaxin/lysophospholipase D expression in intestinal vessels in aggravation of intestinal damage through lymphocyte migration. Lab Invest. 2013 May;93(5):508-19. doi: 10.1038/labinvest.2013.45. PubMed PMID: 23478591.