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
...The organ distribution of 3H lucanthone in mice and 125I lucanthone in rats was determined to learn if lucanthone crossed the blood-brain barrier. Size determinations were made of patients' brain metastases from magnetic resonance images or by computed tomography before and after treatment with 30 Gy whole brain radiation alone or with lucanthone. ...The time course of lucanthone's distribution in brain was identical to that in muscle and heart after intraperitoneal or intravenous administration in experimental animals. Lucanthone, therefore, readily crossed the blood-brain barrier in experimental animals. ...Compared with radiation alone, the tumor regression in patients with brain metastases treated with lucanthone and radiation was accelerated, approaching significance using a permutation test at p=0.0536.

---

Biological Half-Life
A sublethal dose of 100 mg lucanthone hydrochloride/kg (Miracil D, Nilodin; NSC-14574) administered ip into Chinese hamsters (median lethal dose for 30-day survival (LD50/30) of 315 mg/kg) ... Serum concentration of lucanthone hydrochloride in the Chinese hamster, determined spectrophotometrically, reached a peak of 8 microgram/ml by 1.5 hours post inoculation and then decreased exponentially with a half-life of approximately 6 hours, so that by 30 hours post inoculation it was unmeasurable.

Interactions
The interaction of lucanthone and cyclophosphamide (CYC) was investigated in the Chinese hamster in terms of the LD50/7 and LD50/30. These values may be indicative of gastrointestinal stem cell depletion and bone marrow stem cell depletion, respectively. When a nonlethal dose of 100 mg/kg lucanthone preceded CYC injection, the LD50/7 for CYC reached its minimum value of 470 mg/kg at a treatment interval of 10 hours. Lucanthone administered simultaneously with CYC had no effect on the control LD50/7 of 750 mg/kg, and by 48 hours after lucanthone administration the LD50/7 had returned to the control value. When CYC administration preceded that of lucanthone, the LD50/7 reached a minimum of value of 610 mg/kg at an interval of 5 hours; however, for the entire sequence it was approximately 640 mg/kg over all intervals up to 48 hours. The LD50/30 for CYC was only slightly reduced by the presence of lucanthone, indicating that bone marrow sensitivity to CYC was only marginally affected by lucanthone. These data indicate that lucanthone may interact with CYC damage in much the same way as it interacts with radiation damage, viz, by reducing cellular capacity to accumulate and repair sublethal damage.

---

Non-Human Toxicity Values
LD50 Mouse iv 56 mg/kg /Lucanthone/
LD50 Mouse intramuscular 400 mg/kg /Lucanthone/

[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.

One of the SCHISTOSOMICIDES, it has been replaced largely by HYCANTHONE and more recently PRAZIQUANTEL. (From Martindale The Extrapharmacopoeia, 30th ed., p46)

---

Mechanism of Action
The ability of lucanthone to inhibit the normal repair of abasic sites might reflect inhibition of apurinic/apyrimidinic endonuclease (HAP1) by the drug, thereby preventing an early step in the base excision repair pathway. Unrepaired abasic sites prevalent after ionizing radiation are cytotoxic lesions that promote DNA strand breaks. These results suggest a rationale for the joint lethal effects of lucanthone and ionizing radiation in cells and the accelerated tumor regression observed in cancer patients who received the combined therapy.
Addition of lucanthone (1-5 ug/ml) to cultures of Tetrahymena results in a preferential inhibition of the synthesis of ribosomal RNA. Transcriptional studies with isolated nucleoli from Tetrahymena demonstrate that the endogenous RNA polymerases of the r-chromatin (chromatin form of rDNA) do not recognize the normal termination and move into the spacer region distal to the terminator in the presence of lucanthone. ...Lucanthone seems specific in its action on termination as it does not inhibit the elongation process on the chromatin. Among various DNA- binding drugs tested only lucanthone and proflavine are found to cause repression of the termination. The data obtained suggest that the reduced synthesis of rRNA in lucanthone-treated eukaryotic cells is due to lack of reinitiating RNA polymerases possibly caused by improper termination.
Exposure of HeLa cells to lucanthone (3 ug/ml) caused dissociation of a fast-sedimenting duplex DNA complex, as judged by lysis and sedimentation in alkaline sucrose gradients. The effect of lucanthone on the DNA complex resembled that of actinomycin D and ionizing radiation. Protein synthesis inhibitors such as cycloheximide or inhibitors of DNA synthesis such as hydroxyurea did not lead to dissociation of the complex. ...Lucanthone promoted X-ray-induced denaturation of DNA in intact cells, as judged by their nuclear immunoreactivity to antinucleoside antibodies. Lucanthone did not inhibit repair of X-ray-induced DNA single-strand breaks.
Studies were conducted on the stimulatory effect that various nucleic-acid-binding compounds have on the hydrolysis of RNA and polyribonucleotides by pancreatic ribonuclease A and by other ribonucleases. ...Lucanthone... stimulated the hydrolysis of tRNA by pancreatic ribonuclease A. .../In addition,/ lucanthone, stimulated the hydrolysis of tRNA by ribonuclease N1.
For more Mechanism of Action (Complete) data for LUCANTHONE HYDROCHLORIDE (7 total), please visit the HSDB record page.

---

Therapeutic Uses
Lucanthone is an antitumor drug used as an adjuvant in radiation therapy. The drug intercalates into DNA and inhibits topoisomerase II.
Antihelmintic (Schistosoma).

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.

---

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).

View More

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)

---

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).

View More

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

---

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.

---

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