Lucanthone

    WARNING: This product is for research use only, not for human or veterinary use.

MedKoo CAT#: 201780

CAS#: 479-50-5

Description: Lucanthone is orally available thioxanthone-based DNA intercalator and inhibitor of the DNA repair enzyme apurinic-apyrimidinic endonuclease 1 (APEX1 or APE1), with anti-schistosomal and potential antineoplastic activity. Lucanthone intercalates DNA and interferes with the activity of topoisomerases I and II during replication and transcription, thereby inhibiting the synthesis of macromolecules. In addition, this agent specifically inhibits the endonuclease activity of APE1, without affecting its redox activity, resulting in unrepaired DNA strand breaks which may induce apoptosis. Therefore, lucanthone may sensitize tumor cells to radiation and chemotherapy. Furthermore, lucanthone inhibits autophagy through the disruption of lysosomal function. The multifunctional nuclease APE1 is a key component for DNA repair; its expression is often correlated with tumor cell resistance to radio- and chemotherapy. Check for active clinical trials or closed clinical trials using this agent. ( NCI Thesaurus )


Chemical Structure

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Lucanthone
CAS# 479-50-5

Theoretical Analysis

MedKoo Cat#: 201780
Name: Lucanthone
CAS#: 479-50-5
Chemical Formula: C20H24N2OS
Exact Mass: 340.16093
Molecular Weight: 340.48
Elemental Analysis: C, 70.55; H, 7.10; N, 8.23; O, 4.70; S, 9.42

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Synonym: Lucanthone monohydrochloride; NCIMech000830; CCRIS 1106; AIDS013879; AIDS-013879; Thiaxanthenone; miracil D.

IUPAC/Chemical Name: 1-{[2-(diethylamino)ethyl]amino}-4-methyl-9H-thioxanthen-9-one

InChi Key: FBQPGGIHOFZRGH-UHFFFAOYSA-N

InChi Code: 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

SMILES Code: O=C1C2=C(SC3=C1C=CC=C3)C(C)=CC=C2NCCN(CC)CC

Appearance: Solid powder

Purity: >98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO, not in water

Shelf Life: >2 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

Preparing Stock Solutions

The following data is based on the product molecular weight 340.48 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL

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1: Chowdhury SM, Surhland C, Sanchez Z, Chaudhary P, Suresh Kumar MA, Lee S, Peña LA, Waring M, Sitharaman B, Naidu M. Graphene nanoribbons as a drug delivery agent for lucanthone mediated therapy of glioblastoma multiforme. Nanomedicine. 2014 Aug 13. pii: S1549-9634(14)00424-9. doi: 10.1016/j.nano.2014.08.001. [Epub ahead of print] PubMed PMID: 25131339.

2: Naidu MD, Agarwal R, Pena LA, Cunha L, Mezei M, Shen M, Wilson DM 3rd, Liu Y, Sanchez Z, Chaudhary P, Wilson SH, Waring MJ. Lucanthone and its derivative hycanthone inhibit apurinic endonuclease-1 (APE1) by direct protein binding. PLoS One. 2011;6(9):e23679. doi: 10.1371/journal.pone.0023679. Epub 2011 Sep 15. PubMed PMID: 21935361; PubMed Central PMCID: PMC3174134.

3: Carew JS, Espitia CM, Esquivel JA 2nd, Mahalingam D, Kelly KR, Reddy G, Giles FJ, Nawrocki ST. Lucanthone is a novel inhibitor of autophagy that induces cathepsin D-mediated apoptosis. J Biol Chem. 2011 Feb 25;286(8):6602-13. doi: 10.1074/jbc.M110.151324. Epub 2010 Dec 10. PubMed PMID: 21148553; PubMed Central PMCID: PMC3057822.

4: Luo M, Kelley MR. Inhibition of the human apurinic/apyrimidinic endonuclease (APE1) repair activity and sensitization of breast cancer cells to DNA alkylating agents with lucanthone. Anticancer Res. 2004 Jul-Aug;24(4):2127-34. PubMed PMID: 15330152.

5: Mendez F, Goldman JD, Bases RE. Abasic sites in DNA of HeLa cells induced by lucanthone. Cancer Invest. 2002;20(7-8):983-91. PubMed PMID: 12449731.

6: Dassonneville L, Bailly C. Stimulation of topoisomerase II-mediated DNA cleavage by an indazole analogue of lucanthone. Biochem Pharmacol. 1999 Oct 15;58(8):1307-12. PubMed PMID: 10487533.

7: Del Rowe JD, Bello J, Mitnick R, Sood B, Filippi C, Moran J, Freeman K, Mendez F, Bases R. Accelerated regression of brain metastases in patients receiving whole brain radiation and the topoisomerase II inhibitor, lucanthone. Int J Radiat Oncol Biol Phys. 1999 Jan 1;43(1):89-93. PubMed PMID: 9989518.

Lucanthone

10.0mg / Not available


Additional Information

Lucanthone is an orally administered small-molecule which inhibits Topoisomerase II and AP endonuclease. In preclinical tests, lucanthone was shown to enhance the sensitivity of animals to an anticancer agent in a time dependent and reversible manner. Lucanthone has structural and biochemical similarities to Actinomycin D but has no hematological or GI toxicity at clinically tolerated doses. More recent research shows that lucanthone sensitizes tumor cells to radiation and chemotherapy by inhibiting DNA repair (AP endonuclease). Lucanthone is currently in clinical development for the treatment of brain tumors.
 
According to Spectrum Pharmaceuticals's website, Lucanthone inhibits Topoisomerase II and interferes with the repair of DNA damage that is caused by radiation and chemotherapy. Specificity of lucanthone in combination with radiation or chemotherapy for the treatment of brain tumors arises from the fact that lucanthone acts preferentially on cycling cells (most of the normal brain cells are non-cycling) and the fact that lucanthone crosses the blood brain barrier efficiently