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Identification
NameLucanthone
Accession NumberDB04967
TypeSmall Molecule
GroupsApproved, Investigational
Description

One of the schistosomicides, it has been replaced largely by hycanthone and more recently praziquantel. (From Martindale The Extrapharmacopoeia, 30th ed., p46). It is currently being tested as a radiation sensitizer.

Structure
Thumb
Synonyms
1-((2-(Diethylamino)ethyl)amino)-4-methylthioxanthen-9-one
1-{[2-(diethylamino)ethyl]amino}-4-methylthioxanthen-9-one
1-diethylaminoethylethylamino-4-methyl-thioxanthenone
Lucanthone
Lucanthonum
Lucantona
External Identifiers Not Available
Approved Prescription ProductsNot Available
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
Miracil DNot Available
Brand mixturesNot Available
Salts
Name/CASStructureProperties
Lucanthone hydrochloride
Thumb
  • InChI Key: FBQPGGIHOFZRGH-UHFFFAOYSA-N
  • Monoisotopic Mass: 340.16093409
  • Average Mass: 340.482
DBSALT000826
Categories
UNIIFC6D57000M
CAS number479-50-5
WeightAverage: 340.482
Monoisotopic: 340.16093409
Chemical FormulaC20H24N2OS
InChI KeyInChIKey=FBQPGGIHOFZRGH-UHFFFAOYSA-N
InChI
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
IUPAC Name
1-{[2-(diethylamino)ethyl]amino}-4-methyl-9H-thioxanthen-9-one
SMILES
CCN(CC)CCNC1=C2C(=O)C3=CC=CC=C3SC2=C(C)C=C1
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as thiochromenes. These are organosulfur compounds that are analogues to chromene, with the difference that a sulfur atom replaces the oxygen atom.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassThiochromenes
Sub ClassNot Available
Direct ParentThiochromenes
Alternative Parents
Substituents
  • Thiochromene
  • Secondary aliphatic/aromatic amine
  • Benzenoid
  • Heteroaromatic compound
  • Vinylogous amide
  • Tertiary aliphatic amine
  • Tertiary amine
  • Secondary amine
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Amine
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Pharmacology
IndicationIntended for use as a radiation sensitizer in the treatment of brain cancer.
PharmacodynamicsAlthough lucanthone has structural and biochemical similarities to Actinomycin D, it has no hematological or gastro-intestinal toxicity at clinically tolerated doses. In trials, Lucanthone was found to be safe, practical and effective and was proposed for use in clinical protocols for the treatment of cancer. The specificity of lucanthone in combination with radiation 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.
Mechanism of actionRecent data suggests that lucanthone inhibits post-radiation DNA repair in tumor cells. The ability of lucanthone to inhibit AP endonuclease and topoisomerase II probably account for the specific DNA repair inhibition in irradiated cells.
Related Articles
AbsorptionOrally available
Volume of distributionNot Available
Protein bindingNot Available
MetabolismNot Available
Route of eliminationNot Available
Half lifeNot Available
ClearanceNot Available
ToxicityNot Available
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9644
Blood Brain Barrier+0.9538
Caco-2 permeable+0.5555
P-glycoprotein substrateSubstrate0.8992
P-glycoprotein inhibitor IInhibitor0.62
P-glycoprotein inhibitor IINon-inhibitor0.7254
Renal organic cation transporterNon-inhibitor0.5391
CYP450 2C9 substrateNon-substrate0.6567
CYP450 2D6 substrateSubstrate0.545
CYP450 3A4 substrateSubstrate0.5259
CYP450 1A2 substrateInhibitor0.8476
CYP450 2C9 inhibitorNon-inhibitor0.8837
CYP450 2D6 inhibitorInhibitor0.704
CYP450 2C19 inhibitorNon-inhibitor0.7842
CYP450 3A4 inhibitorNon-inhibitor0.5884
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.6989
Ames testAMES toxic0.9107
CarcinogenicityNon-carcinogens0.761
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.5482 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.6183
hERG inhibition (predictor II)Inhibitor0.8499
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
StateSolid
Experimental PropertiesNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.00315 mg/mLALOGPS
logP4.72ALOGPS
logP5.02ChemAxon
logS-5ALOGPS
pKa (Strongest Acidic)18.84ChemAxon
pKa (Strongest Basic)8.69ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area32.34 Å2ChemAxon
Rotatable Bond Count6ChemAxon
Refractivity106.01 m3·mol-1ChemAxon
Polarizability39.6 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis ReferenceNot Available
General References
  1. 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:15330152 ]
  2. 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:9989518 ]
External Links
ATC CodesNot Available
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
inhibitor
General Function:
Ubiquitin binding
Specific Function:
Control of topological states of DNA by transient breakage and subsequent rejoining of DNA strands. Topoisomerase II makes double-strand breaks. Essential during mitosis and meiosis for proper segregation of daughter chromosomes. May play a role in regulating the period length of ARNTL/BMAL1 transcriptional oscillation (By similarity).
Gene Name:
TOP2A
Uniprot ID:
P11388
Molecular Weight:
174383.88 Da
References
  1. Bases RE, Mendez F: Topoisomerase inhibition by lucanthone, an adjuvant in radiation therapy. Int J Radiat Oncol Biol Phys. 1997 Mar 15;37(5):1133-7. [PubMed:9169823 ]
  2. 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:10487533 ]
  3. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
inhibitor
General Function:
Uracil dna n-glycosylase activity
Specific Function:
Multifunctional protein that plays a central role in the cellular response to oxidative stress. The two major activities of APEX1 in DNA repair and redox regulation of transcriptional factors. Functions as a apurinic/apyrimidinic (AP) endodeoxyribonuclease in the DNA base excision repair (BER) pathway of DNA lesions induced by oxidative and alkylating agents. Initiates repair of AP sites in DNA...
Gene Name:
APEX1
Uniprot ID:
P27695
Molecular Weight:
35554.165 Da
References
  1. 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:15330152 ]
3. DNA
Kind
Nucleotide
Organism
Human
Pharmacological action
yes
Actions
intercalation
General Function:
Used for biological information storage.
Specific Function:
DNA contains the instructions needed for an organism to develop, survive and reproduce.
Molecular Weight:
2.15 x 1012 Da
References
  1. Milligan AJ, Metz JA, Leeper DB: The effect of lucanthone on sublethal radiation damage, in vivo. Int J Radiat Oncol Biol Phys. 1984 Dec;10(12):2309-13. [PubMed:6392224 ]
  2. Bailly C, Waring MJ: Preferential intercalation at AT sequences in DNA by lucanthone, hycanthone, and indazole analogs. A footprinting study. Biochemistry. 1993 Jun 15;32(23):5985-93. [PubMed:8389585 ]
  3. 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:10487533 ]
Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
inhibitor
General Function:
Poly(a) rna binding
Specific Function:
Releases the supercoiling and torsional tension of DNA introduced during the DNA replication and transcription by transiently cleaving and rejoining one strand of the DNA duplex. Introduces a single-strand break via transesterification at a target site in duplex DNA. The scissile phosphodiester is attacked by the catalytic tyrosine of the enzyme, resulting in the formation of a DNA-(3'-phosphot...
Gene Name:
TOP1
Uniprot ID:
P11387
Molecular Weight:
90725.19 Da
References
  1. Bases RE, Mendez F: Topoisomerase inhibition by lucanthone, an adjuvant in radiation therapy. Int J Radiat Oncol Biol Phys. 1997 Mar 15;37(5):1133-7. [PubMed:9169823 ]
  2. 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:10487533 ]
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Drug created on October 21, 2007 16:23 / Updated on September 16, 2013 17:26