Hycanthone has an 80 nM IC50 to prevent APE1 from cleaving apurinic plasmid DNA [1]. Cycloheximide (CHX) stimulates APE1 cleavage, which is blocked by 1% DMSO at concentrations of 0.05-100 µM for a duration of two hours [1]. Cell viability decreased more and more with ethylenedione concentrations of 20 mg/mL or more. According to the findings, there was a gradual decrease in viral interferon production of up to 73% when the concentration of ethylenedione was increased from 0.1 to 10 μg/mL, in comparison to the control group.

The findings demonstrated that following acetylenone treatment, the amount of tritiated thymidine incorporated into the TCA-precipitable material of adult susceptible worms gradually decreased. In all experiments, acetylenone had no effect at all on young worms. Male worms that had received acetylenone treatment may have recovered somewhat from their initial low incorporation levels. Within the first four days of treatment, drug-sensitive worms' ability to incorporate tritiated leucine was decreased by 40 to 50 percent. According to the results, both ribosomal RNA species were at least 80% smaller seven days following Hycanthone therapy when compared to worms that had not received any treatment, suggesting that larger precursor molecules may have accumulated [2].

Absorption, Distribution and Excretion
In male Sprague-Dawley rats and in rhesus monkeys of both sexes receiving single im injections of randomly tritiated hycanthone mesylate at doses in the range of those therapeutically recommended for man (3 mg/kg bw), peak blood and tissue levels were found about 30-60 minutes after administration. Highest concentrations were observed in the liver, spleen, kidneys and adrenals but decreased to <20% of the administered dose in 48-72 hr. Unchanged drug was found in blood and tissues, except in the liver where rapid conversion to hycanthone sulphoxide occured in rats and to the N-de-ethylated metabolite in monkeys.
The rate of excretion of labelled hycanthone has been determined in bile and urine from three strains of rats (Sprague-Dawley, hooded and Gunn), and from dogs, cats, rabbits and monkeys. Bile was the major route of excretion in all species; the half-life for excretion of total radioactivity ranged from 1.6 to 3.0 hours. Relatively little of the radioactivity was found in the urine, except in the monkey and notably in the cat. Most of the radioactivity in the bile and urine was found in conjugated form, or as polar metabolites; cat urine, however contained a high percentage of hycanthone and less polar metabolites. Some fifteen metabolites have been seen in bile, and/or urine, and nine from in vitro incubations with microsomal preparations. Five of these, including hycanthone, have been chemically characterized, and two others tentatively identified.

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Metabolism / Metabolites
In male Sprague-Dawley rats and in rhesus monkeys of both sexes receiving single im injections of randomly tritiated hycanthone mesylate at doses in the range of those therapeutically recommended for man (3 mg/kg bw), peak blood and tissue levels were found about 30-60 minutes after administration. ... Unchanged drug was found in blood and tissues, except in the liver where rapid conversion to hycanthone sulphoxide occured in rats and to the N-de-ethylated metabolite in monkeys.
The rate of excretion of labelled hycanthone has been determined in bile and urine from three strains of rats (Sprague-Dawley, hooded and Gunn), and from dogs, cats, rabbits and monkeys. ... Most of the radioactivity in the bile and urine was found in conjugated form, or as polar metabolites; cat urine, however contained a high percentage of hycanthone and less polar metabolites. Some fifteen metabolites have been seen in bile, and/or urine, and nine from in vitro incubations with microsomal preparations. Five of these, including hycanthone, have been chemically characterized, and two others tentatively identified.

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Biological Half-Life
The rate of excretion of labelled hycanthone has been determined in bile and urine from three strains of rats (Sprague-Dawley, hooded and Gunn), and from dogs, cats, rabbits and monkeys. Bile was the major route of excretion in all species; the half-life for excretion of total radioactivity ranged from 1.6 to 3.0 hours. ...

Interactions
Interactions of caffeine with chemicals known for their effects on chromosomal segregation during meiosis of Saccharomyces cerevisiae were studied. It appears that caffeine does interfere with the action of other compounds during the different phases of meiosis. Treatments with methyl methanesulphonate (MMS) and cadmium chloride (CdCl2) resulted in a synergistic effect consisting of an increase in the frequency of recombination. The greatest effects were found on the induction of diploid spores: MMS, hycanthone, and distamycin demonstrated strong, benlate little synergistic action. ...Concerning disomic induction: caffeine reduced (or left unchanged) the effect on non-disjunction when MMS and hycanthone were used. /Salt not specified/

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Non-Human Toxicity Values
LD50 Rat oral 980 mg/kg /Hycanthone/
LD50 Rat sc 286 mg/kg /Hycanthone/
LD50 Rat iv 75 mg/kg /Hycanthone/
LD50 Mouse oral 1120 mg/kg /Hycanthone/
For more Non-Human Toxicity Values (Complete) data for HYCANTHONE MESYLATE (12 total), please visit the HSDB record page.

[1]. Lucanthone and its derivative hycanthone inhibit apurinic endonuclease-1 (APE1) by direct protein binding. PLoS One. 2011;6(9):e23679.

[2]. Effect of hycanthone administered in vivo upon the incorporation of radioactive precursors into macromolecules of Schistosoma mansoni. Mol Biochem Parasitol. 1983 Jun;8(2):99-107.

[3]. Action of antischistosomal drugs, hycanthone and its analog 1A-4 N-oxide, on viral interferon induction. J Toxicol Environ Health. 1980 Jul;6(4):705-12.

Hycanthone is an odorless canary yellow to yellow-orange crystalline powder. Bitter taste. (NTP, 1992)
Hycanthone methanesulfonate is an odorless yellow to yellow-orange powder. Bitter taste. (NTP, 1992)
Hycanthone is a thioxanthen-9-one compound having a hydroxymethyl substituent at the 1-position and a 2-[(diethylamino)ethyl]amino substituent at the 4-position. It was formerly used (particularly as the monomethanesulfonic acid salt) as a schistosomicide for individual or mass treatement of infection with Schistosoma haematobium and S. mansoni, but due to its toxicity and concern about possible carcinogenicity, it has been replaced by other drugs such as praziquantel. It has a role as a schistosomicide drug and a mutagen. It is functionally related to a lucanthone. It is a conjugate base of a hycanthone(1+).
Potentially toxic, but effective antischistosomal agent, it is a metabolite of LUCANTHONE. Hycanthone was approved by the FDA in 1975 but is no longer used.
Hycanthone is a thioxanthene derivative of lucanthone with anti-schistosomal activity and potential antineoplastic activity. Hycanthone interferes with parasite nerve function, resulting in parasite paralysis and death. This agent also intercalates into DNA and inhibits RNA synthesis in vitro. (NCI04)
Potentially toxic, but effective antischistosomal agent, it is a metabolite of LUCANTHONE.

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Mechanism of Action
...A preferential binding of hycanthone to heterochromatin could be demonstrated for the nuclei of the Malpighian tubules of Triatoma infestans. In other cellular systems like cattle kidney cells in culture, plant cells, and mouse lymphocytes, the drug could be demonstrated to bind heterochromatin and euchromatin, irrespective of the packing state of the latter. When penetrating the various heterochromatin types (with the exception of T. infestans), the drug induced a chromatin loosening that could favor incidence of chromatin breaks. The variation of hycanthone binding to DNA in different cell types is possibly related to differences in composition, stereo-arrangement and stability of the DNA-protein complexes involved.
...Inhibition of RNA synthesis can be a possible explanation for the mechanism of the schistosomicidal action of hycanthone. /Salt not specified/
...Hycanthone was shown to be a very potent inhibitor of monoamine oxidases from worms and mouse liver. Hycanthone also inhibited the specific and nonspecific cholinesterases of S. mansoni, but cholinesterase from mouse brain was not affected significantly by this drug. ... /Salt not specified/
...Analysis of the ACh induced noise revealed that 1 microM hycanthone slightly increased the channel lifetime whereas the single channel conductance was not affected. It was concluded that the primary site of action of hycanthone is the 'transient state' or ACh bound but closed conformation of the ACh receptor ion channel, but this drug also has other sites of action (presynaptic nerve terminal and open conformation of ACh receptor-ion channel complex). /Salt not specified/
For more Mechanism of Action (Complete) data for HYCANTHONE MESYLATE (8 total), please visit the HSDB record page.

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Therapeutic Uses
This chemical is a thioxanthone. It is a lucanthone metabolite. Clinical use of this compound has been sharply reduced because of reports that it is mutagenic and carcinogenic. It is not available in the United States. /Hycanthone/
Used in treatment of schistosomiasis.

356.156

3105-97-3

3105-97-3 US Etrenol;

3634

Yellow to orange solid powder

1.25g/cm3

570.5ºC at 760mmHg

approx 143ºC

298.9ºC

1.658

3.733

2

5

7

25

443

0

O=C1C2=C(SC3=C1C=CC=C3)C(CO)=CC=C2NCCN(CC)CC

MFZWMTSUNYWVBU-UHFFFAOYSA-N

InChI=1S/C20H24N2O2S/c1-3-22(4-2)12-11-21-16-10-9-14(13-23)20-18(16)19(24)15-7-5-6-8-17(15)25-20/h5-10,21,23H,3-4,11-13H2,1-2H3

1-[2-(diethylamino)ethylamino]-4-(hydroxymethyl)thioxanthen-9-one

Hycanthone

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~12.5 mg/mL (~35.07 mM)

Solubility in Formulation 1: ≥ 1.25 mg/mL (3.51 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 12.5 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: 1.25 mg/mL (3.51 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 12.5 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 1.25 mg/mL (3.51 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 12.5 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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 (Please use freshly prepared in vivo formulations for optimal results.)