Sulfanthone hydrochloride is a new autophagy inhibitor that can promote cathepsin D-mediated apoptosis. To evaluate the anticancer efficacy of sulfanthone hydrochloride, cell viability was determined by MTT assay. Sulfanthone hydrochloride reduced cell viability to a same level in seven breast cancer cell lines. Furthermore, direct comparison showed that sulfanthone hydrochloride was more effective than chloroquine (CQ) in lowering breast cancer cell viability, with an average IC50 of 7.2 μM compared to 66 μM for CQ. Comparable results were achieved by evaluating cell viability of two representative cell lines (MDA-MB-231 and BT-20) by ATPlite assay and trypan blue exclusion technique [2].

Absorption, Distribution and Excretion
…To understand whether lucanone can cross the blood-brain barrier, we measured the organ distribution of 3H lucanone in mice and 125I lucanone in rats. Before and after treatment with 30 Gy whole-brain radiotherapy (alone alone or in combination), we measured the size of brain metastases using magnetic resonance imaging or computed tomography. …In experimental animals, the distribution time course of lucanone in brain tissue was similar to that in muscle and heart after intraperitoneal or intravenous injection. Therefore, lucanone can easily cross the blood-brain barrier in experimental animals. …Compared to radiotherapy alone, patients with brain metastases treated with lucanone combined with radiotherapy showed faster tumor regression, with the replacement test result approaching significance (p=0.0536).

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Biological Half-Life
Intraperitoneal injection of 100 mg/kg of lucane hydrochloride (Miracil D, Nilodin; NSC-14574) into Chinese hamsters (LD50/30 for 30-day survival is 315 mg/kg)... The concentration of lucane hydrochloride in the serum of Chinese hamsters was determined by spectrophotometry. It reached a peak of 8 μg/ml 1.5 hours after inoculation, and then decreased exponentially. The half-life was about 6 hours, so it could not be detected 30 hours after inoculation.

Interactions
This study investigated the interaction between lucanone and cyclophosphamide (CYC) in Chinese hamsters and determined their LD50/7 and LD50/30 values. These values may indicate the depletion of gastrointestinal and bone marrow stem cells, respectively. When a non-lethal dose of 100 mg/kg lucanone was administered before CYC injection, the LD50/7 of CYC reached its lowest value of 470 mg/kg after a 10-hour dosing interval. Co-administration of lucanone and CYC had no effect on the LD50/7 of the control group (750 mg/kg), and the LD50/7 recovered to the control value 48 hours after lucanone administration. When CYC was administered before lucanone, the LD50/7 reached its lowest value of 610 mg/kg after a 5-hour dosing interval; however, throughout the experiment, the dose was approximately 640 mg/kg at all time intervals up to 48 hours. The presence of lucanone only slightly reduced the LD50/30 of cyclophosphamide (CYC), indicating that lucanone has minimal effect on bone marrow CYC sensitivity. These data suggest that lucanone may interact with CYC damage in a similar manner to radiation damage, namely by reducing cell accumulation and repairing sublethal damage.

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Non-human toxicity values
Mouse intravenous LD50: 56 mg/kg /lucanone/
Mouse intramuscular LD50: 400 mg/kg /lucanone/

[1]. Chowdhury SM, et al. Graphene nanoribbons as a drug delivery agent for lucanthone mediated therapy of glioblastoma multiforme. Nanomedicine. 2015 Jan;11(1):109-18.
[2]. Carew JS, et al. Lucanthone is a novel inhibitor of autophagy that induces cathepsin D-mediated apoptosis. J Biol Chem. 2011 Feb 25;286(8):6602-13.

Lucanone is an insecticide used to kill schistosomiasis, but it has been widely replaced by drugs such as hymexazol and praziquantel. (Excerpt from Martindale Pharmacopoeia, 30th edition, p. 46)
Mechanism of Action
The ability of lucanone to inhibit the normal repair of abase sites may reflect its inhibitory effect on depurinyl/depyrimidine endonuclease (HAP1), thereby preventing an early step in the base excision repair pathway. The unrepaired abase sites prevalent after ionizing radiation are cytotoxic damage that promotes DNA strand breaks. These results suggest the plausibility of the combined lethal effects of lucanone and ionizing radiation on cells and the accelerated tumor regression in cancer patients receiving combined therapy.
The addition of lucanone (1-5 μg/ml) to Tetrahymena cultures preferentially inhibits ribosomal RNA synthesis. Transcriptional studies of nucleoli isolated from Tetrahymena showed that, in the presence of lucanone, endogenous RNA polymerases of r-chromatin (the chromatin form of rDNA) failed to recognize normal termination sites and instead moved to the spacer region distal to the terminator. …Lucanone appears to have a specific effect on termination, as it does not inhibit chromatin elongation. Of the various DNA-binding agents tested, only lucanone and profenoflavone were found to inhibit termination. The data suggest that the reduced rRNA synthesis in lucanone-treated eukaryotic cells is due to insufficient RNA polymerase restarting ability caused by abnormal RNA polymerase termination. HeLa cells exposed to lucanone (3 μg/ml) showed dissociation of rapidly settling double-stranded DNA complexes via alkaline sucrose gradient centrifugation and sedimentation experiments. The effect of lucanone on this DNA complex is similar to that of actinomycin D and ionizing radiation. Protein synthesis inhibitors (such as cyclohexylimide) or DNA synthesis inhibitors (such as hydroxyurea) did not induce dissociation of the complex. ...Lucanone promotes X-ray-induced denaturation of DNA in intact cells, which can be determined by the nuclear immunoreactivity to nucleoside antibodies. Lucanone does not inhibit the repair of X-ray-induced DNA single-strand breaks. Researchers have investigated the stimulatory effects of various nucleic acid-binding compounds on pancreatic ribonuclease A and other ribonucleases on the hydrolysis of RNA and polynucleotides. ...Lucanone...stimulates pancreatic ribonuclease A on the hydrolysis of tRNA. ...Furthermore, lucanone also stimulates ribonuclease N1 on the hydrolysis of tRNA. For more complete data on the mechanisms of action of lucanone hydrochloride (7 types), please visit the HSDB record page.

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Therapeutic Uses
Lucanone is an antitumor drug used as an adjunct to radiotherapy. This drug can intercalate into DNA and inhibit topoisomerase II.
Antidote (Schistosomiasis).

C20H24N2OS.CL-

375.93536

376.138

548-57-2

Lucanthone;479-50-5

11054

Yellow crystals from alcohol

512.4ºC at 760 mmHg

195-196ºC

263.7ºC

5.351

2

4

6

25

426

0

CCN(CC)CCNC1=C2C(=O)C3=CC=CC=C3SC2=C(C)C=C1.Cl

LAOOXBLMIJHMFO-UHFFFAOYSA-N

InChI=1S/C20H24N2OS.ClH/c1-4-22(5-2)13-12-21-16-11-10-14(3)20-18(16)19(23)15-8-6-7-9-17(15)24-20;/h6-11,21H,4-5,12-13H2,1-3H3;1H

1-[2-(diethylamino)ethylamino]-4-methylthioxanthen-9-one;hydrochloride

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)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*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.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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