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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
SynonymLanguageCode
1-((2-(Diethylamino)ethyl)amino)-4-methylthioxanthen-9-oneNot AvailableNot Available
1-{[2-(diethylamino)ethyl]amino}-4-methylthioxanthen-9-oneNot AvailableNot Available
1-diethylaminoethylethylamino-4-methyl-thioxanthenoneNot AvailableNot Available
LucanthoneNot AvailableNot Available
LucanthonumLatinINN
LucantonaSpanishINN
Prescription ProductsNot Available
Generic Prescription ProductsNot Available
Over the Counter ProductsNot 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
CAS number479-50-5
WeightAverage: 340.482
Monoisotopic: 340.16093409
Chemical FormulaC20H24N2OS
InChI KeyFBQPGGIHOFZRGH-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.
AbsorptionOrally available
Volume of distributionNot Available
Protein bindingNot Available
Metabolism
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 substrateNon-inhibitor0.8837
CYP450 2D6 substrateInhibitor0.704
CYP450 2C19 substrateNon-inhibitor0.7842
CYP450 3A4 substrateNon-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
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 Reference
  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
  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
External Links
ATC CodesNot Available
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available

Targets

1. DNA topoisomerase 2-alpha

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
DNA topoisomerase 2-alpha P11388 Details

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
  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
  3. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

2. DNA-(apurinic or apyrimidinic site) lyase

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
DNA-(apurinic or apyrimidinic site) lyase P27695 Details

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

3. DNA

Kind: nucleotide

Organism: Human

Pharmacological action: yes

Actions: intercalation

Components

Name UniProt ID Details

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
  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
  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

4. DNA topoisomerase 1

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
DNA topoisomerase 1 P11387 Details

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
  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

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Drug created on October 21, 2007 16:23 / Updated on September 16, 2013 17:26