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 male and female rhesus monkeys, a single intramuscular injection of randomly labeled tritium-labeled hexaconazole mesylate (dose range consistent with the human therapeutic recommendation, 3 mg/kg body weight) resulted in peak plasma and tissue concentrations approximately 30–60 minutes post-administration. The highest drug concentrations were observed in the liver, spleen, kidneys, and adrenal glands, but decreased to less than 20% of the administered dose within 48–72 hours. Unaltered drug was detected in blood and tissues, except in the liver. In the liver, the drug in rats was rapidly converted to hexaconazole sulfoxide, while in monkeys it was converted to an N-deethyl metabolite. The excretion rates of labeled hexaconazole in bile and urine were determined in three rat strains (Sprague-Dawley, hooded, and Gunn), as well as in dogs, cats, rabbits, and monkeys. Bile was the primary route of excretion in all species; the half-life of total radioactive excretion ranged from 1.6 to 3.0 hours. Except in monkeys and cats, the radioactivity levels in urine are relatively low. Most of the radioactivity in bile and urine exists in bound or polar metabolites; however, cat urine contains a high proportion of hemikacin and less polar metabolites. Approximately 15 metabolites have been detected in bile and/or urine, and 9 metabolites have been detected in in vitro microsomal incubation. The chemical properties of 5 of these (including hemikacin) have been characterized, and the remaining 2 have been preliminarily identified. Metabolites/Metabolic Substances In male Sprague-Dawley rats and male and female rhesus monkeys, peak plasma and tissue concentrations are reached approximately 30–60 minutes after a single intramuscular injection of randomly labeled tritium mesylate hemikacin (dose range equivalent to the human therapeutic recommended dose (3 mg/kg body weight)). Unaltered drug was detected in blood and tissues except in the liver. In the liver, the drug in rats is rapidly converted to hemikacin sulfoxide, while in monkeys it is converted to an N-deethyl metabolite. The excretion rates of labeled hemconone in the bile and urine of three strains of rats (Sprague-Dawley, hooded, and Gunn) as well as dogs, cats, rabbits, and monkeys have been determined. Most of the radioactive material in bile and urine exists in bound or polar metabolites; however, cat urine contains a high proportion of hemconone and less polar metabolites. Approximately 15 metabolites were detected in bile and/or urine, and 9 metabolites were detected in in vitro microsomal incubation assays. The chemical properties of five of these compounds (including hemconone) have been characterized, and two others have been preliminarily identified.
Biological Half-Life
The excretion rates of labeled hemconone in the bile and urine of three strains of rats (Sprague-Dawley, hooded, and Gunn) as well as dogs, cats, rabbits, and monkeys have been determined. Bile is the primary excretion route in all species; the excretion half-life of total radioactive material ranges from 1.6 to 3.0 hours.

Interactions
This study investigated the interactions between caffeine and chemicals known to affect chromosome segregation during meiosis in Saccharomyces cerevisiae. Results showed that caffeine does indeed interfere with the effects of other compounds at different stages of meiosis. Treatment with methyl methanesulfonate (MMS) and cadmium chloride (CdCl2) produced synergistic effects, manifested as an increase in recombination frequency. The most significant effects were observed in the induction of diploid spores: MMS, hemikacin, and destamycin exhibited strong synergistic effects, while benzoates showed weaker synergistic effects. …Regarding diploid induction: when using MMS and hemikacin, caffeine reduced (or remained unchanged) the effect on non-segregation. /Unspecified salt/

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Non-human toxicity values
Oral LD50 in rats: 980 mg/kg /Hyconone/
Subcutaneous LD50 in rats: 286 mg/kg /Hyconone/
Intravenous LD50 in rats: 75 mg/kg /Hyconone/
Oral LD50 in mice: 1120 mg/kg /Hyconone/
For more complete non-human toxicity data for hyconone mesylate (out of 12), please visit the HSDB records 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 with a bitter taste. (NTP, 1992)
Hycanthone mesylate is an odorless, yellow to yellow-orange powder with a bitter taste. (NTP, 1992)
Hycanthone is a thioxanthracene-9-one compound with a hydroxymethyl substituent at position 1 and a 2-[(diethylamino)ethyl]amino substituent at position 4. It was once used as a schistosomiasis killer (especially monomethyl mesylate) for individual or group treatment of Schistosoma haematobium and Schistosoma mansoni infections, but has been replaced by other drugs such as praziquantel due to its toxicity and potential carcinogenicity. It is both a schistosomiasis killer and a mutagen. It is functionally related to lucanone. It is the conjugate base of Hycanthone (1+).
It is a potentially toxic but effective antischistosome drug and a metabolite of lucanone. Hecanone was approved by the U.S. Food and Drug Administration (FDA) in 1975, but is no longer in use. Hecanone is a thioxanthate derivative of lucanone and possesses anti-schistosomiasis activity and potential antitumor activity. Hecanone interferes with the parasite's neural function, leading to paralysis and death. The drug can also intercalate into DNA and inhibit RNA synthesis in vitro. (NCI04) This is a potentially toxic but effective anti-schistosomiasis drug, a metabolite of lucanone. Mechanism of Action: ...In the nuclei of Malpighian tubule cells of the triatoma infestans, hecanone has been shown to preferentially bind to heterochromatin. In other cellular systems, such as cultured bovine kidney cells, plant cells, and mouse lymphocytes, the drug has also been shown to bind to both heterochromatin and euchromatin, regardless of the latter's arrangement. When the drug penetrates into various types of heterochromatin (except in triatoma infestans), it induces chromatin loosening, potentially promoting chromatin breakage. The differences in hemodiazone binding to DNA in different cell types may be related to the composition, stereostructure, and stability of the DNA-protein complex involved. ...Inhibition of RNA synthesis may be one explanation for the mechanism of hemodiazone's action against Schistosoma. ...Studies have shown that hemodiazone is a potent inhibitor of monoamine oxidase in worms and mouse liver. Hemodiazone also inhibits specific and non-specific cholinesterases in Schistosoma mansoni, but has no significant effect on mouse brain cholinesterase. ... ...Analysis of acetylcholine-induced noise showed that 1 μM hemodiazone slightly prolonged channel lifetime without affecting single-channel conductance. The study concludes that the main site of action of hemodiazone is the "transient state" of acetylcholine receptor ion channels or the state where acetylcholine is bound but in a closed conformation, but the drug also has other sites of action (presynaptic nerve endings and the open conformation of acetylcholine receptor-ion channel complexes). /Unspecified Salt/
For more complete data on the mechanism of action of hymexazol mesylate (8 compounds total), please visit the HSDB record page.

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Therapeutic Use
This compound is a thioxanone compound and a metabolite of lucanone. Its clinical use has been significantly reduced due to reported mutagenic and carcinogenic properties. It is not available in the United States. /Hymexazol/
Used to treat 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.)