Lucanthone targets the DNA repair enzyme apurinic-apyrimidinic endonuclease 1 (APE1/APEX1). It functions as an endonuclease inhibitor, blocking the DNA repair activity of APE1. The compound also acts as a DNA intercalator, intercalating into DNA and disrupting DNA structure. Additionally, lucanthone is a novel inhibitor of autophagy that induces cathepsin D-mediated apoptosis.

Lucanthone is an innovative inhibitor of autophagy that triggers apoptosis mediated by cathepsin D. The MTT assay was used to assess cell viability in order to investigate suanthone's anticancer properties. In seven different cell lines of breast cancer, sulfanthone similarly decreased cell viability. Moreover, a direct comparison demonstrated that suanthone had a lower average IC50 of 7.2 μM compared to 66 μM for chloroquine (CQ) in terms of lowering the viability of breast cancer cells. By using the trypan blue exclusion method and the ATPlite test to measure the cell viability of two typical cell lines (MDA-MB-231 and BT-20), comparable findings were achieved [2].
In vitro, lucanthone inhibits the DNA repair enzyme APE1, which plays a role in the base excision repair pathway. By inhibiting APE1, the compound prevents the repair of DNA damage, leading to the accumulation of DNA lesions and cell death. Lucanthone also induces autophagy inhibition and cathepsin D-mediated apoptosis. Cell viability is commonly measured by MTT assay.

In vivo, lucanthone has been studied for its anti-schistosomal activity and potential antineoplastic effects. The compound is orally available. As an APE1 inhibitor and DNA intercalator, it would be expected to have antitumor activity in vivo. Specific in vivo efficacy data and dosing regimens are limited in publicly available sources.

Non-cellular enzyme assays for lucanthone involve measuring APE1 endonuclease activity inhibition. The enzyme is incubated with DNA substrate containing an abasic site and varying concentrations of lucanthone. Cleavage of the DNA substrate is measured by gel electrophoresis or fluorescence-based assays. IC₅₀ values are calculated from inhibition curves.

In vitro cellular experiments involve treating cancer cell lines with lucanthone at various concentrations. Cell viability is measured using MTT or similar assays. Autophagy inhibition is assessed by measuring LC3-II accumulation and p62 levels by Western blot. Apoptosis is detected by measuring cathepsin D activity and by standard apoptosis assays such as Annexin V staining.

In vivo animal studies for lucanthone involve tumor xenograft models or schistosomiasis models. The compound is administered orally. Tumor volume or parasite burden is measured to assess efficacy. Survival is monitored as a key endpoint. Specific protocols are described in the primary literature.

Absorption, Distribution and Excretion
Oral Active Ingredients

Lucanthone is orally available. It has a molecular weight of 340.48 g/mol and a molecular formula of C₂₀H₂₄N₂OS. The compound is soluble in DMSO (33 mg/mL). Storage: powder at -20°C for 3 years; in solvent at -80°C for 6 months.

Specific toxicity data for lucanthone is limited. As an APE1 inhibitor, DNA intercalator, and autophagy inhibitor, it would be expected to have cytotoxic effects. The compound is for research purposes only and should be handled with appropriate safety precautions.

[1]. Graphene nanoribbons as a drug delivery agent for lucanthone mediated therapy of glioblastoma multiforme. Nanomedicine. 2015 Jan;11(1):109-18.

[2]. 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 a thioxanthracene-9-one compound with a methyl substituent at position 1 and a 2-[(diethylamino)ethyl]amino substituent at position 4. It was previously used to treat schistosomiasis. It is a prodrug, metabolized to hycanone. Lucanone has various pharmacological effects, including schistosomiasis control, antitumor activity, photosensitizer, EC 5.99.1.2 (DNA topoisomerase) inhibitor, EC 5.99.1.3 (DNA topoisomerase (ATP hydrolysis)) inhibitor, prodrug, adjuvant, and mutagen. As a schistosomiasis control, lucanone has been largely replaced by hycanone and praziquantel. (Excerpt from Martindale Pharmacopoeia, 30th edition, p. 46) Currently, it is being tested as a radiosensitizer. Lucanone is an orally administered thioxanone-based DNA intercalator and an inhibitor of the DNA repair enzyme depurine-depyrimidine endonuclease 1 (APEX1 or APE1), possessing anti-schistosomiasis and potential antitumor activity. Lucanone intercalates into DNA, interfering with the activity of topoisomerases I and II during replication and transcription, thereby inhibiting the synthesis of macromolecules. Furthermore, this drug specifically inhibits the endonuclease activity of APE1 without affecting its redox activity, leading to unrepaired DNA strand breaks and potentially inducing apoptosis. Therefore, lucanone may enhance the sensitivity of tumor cells to radiation and chemotherapy. Additionally, lucanone inhibits autophagy by disrupting lysosomal function. The multifunctional nuclease APE1 is a key component of DNA repair; its expression is often associated with tumor cell resistance to radiotherapy and chemotherapy. As a schistosomiasis-killing agent, it has been widely superseded by hycanthone and, more recently, praziquantel. (Excerpt from Martindale Pharmacopoeia, 30th edition, page 46)
See also: Thioxanone (note moved here).
Indications
Intended use as a radiosensitizer in the treatment of brain cancer.
Mechanism of Action
Recent data indicate that lucanone inhibits post-radiation DNA repair in tumor cells. The ability of lucanone to inhibit AP endonuclease and topoisomerase II may explain its specific inhibition of DNA repair in irradiated cells.
Pharmacodynamics
Although lucanone is structurally and biochemically similar to actinomycin D, it has no hematologic or gastrointestinal toxicity at clinically tolerated doses. In trials, lucanone has been shown to be safe, practical, and effective, and is recommended for use in clinical cancer treatment regimens. The specificity of lucanone in combination with radiotherapy for brain tumors stems from the fact that lucanone preferentially acts on proliferating cells (most normal brain cells do not proliferate) and that lucanone can effectively cross the blood-brain barrier.
Lucanthone is an orally available thioxanthone-based DNA intercalator and inhibitor of the DNA repair enzyme APE1. It is also a novel inhibitor of autophagy that induces cathepsin D-mediated apoptosis. The compound has anti-schistosomal and potential antineoplastic activity. This product is for research purposes only and is not for human therapeutic use.

C20H24N2OS

340.48

340.161

479-50-5

Lucanthone hydrochloride;548-57-2

10180

Off-white to orange solid powder

1.184g/cm3

512.4ºC at 760 mmHg

195-196ºC

263.7ºC

1.3E-10mmHg at 25°C

1.638

4.549

1

4

6

24

426

0

FBQPGGIHOFZRGH-UHFFFAOYSA-N

InChI=1S/C20H24N2OS/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

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

CCRIS 1106; NCIMech000830; Lucanthone monohydrochloride

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 : ~25 mg/mL (~73.43 mM)

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.)