NAV

Lucanthone

Identification

Generic Name
Lucanthone
DrugBank Accession Number
DB04967
Background

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.

Type
Small Molecule
Groups
Investigational
Structure
3D
Similar Structures
Weight
Average: 340.482
Monoisotopic: 340.16093409
Chemical Formula
C20H24N2OS
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
Poor quality drug data slowing you down?
Unlock 38% more drug discovery time and eliminate decision-making doubts with this one-stop guide to quality drug data.
Download eBook
Poor quality drug data slowing you down?
Download eBook

Pharmacology

Indication

Intended for use as a radiation sensitizer in the treatment of brain cancer.

Reduce drug development failure rates
Build, train, & validate machine-learning models
with evidence-based and structured datasets.
See how
Build, train, & validate predictive machine-learning models with structured datasets.
See how
Contraindications & Blackbox Warnings
Prevent Adverse Drug Events Today
Tap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.
Learn more
Avoid life-threatening adverse drug events with our Clinical API
Learn more
Pharmacodynamics

Although 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 action

Recent 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.

TargetActionsOrganism
ADNA topoisomerase 2-alpha
inhibitor
Humans
ADNA-(apurinic or apyrimidinic site) lyase
inhibitor
Humans
ADNA
intercalation
Humans
ADNA topoisomerase 1
inhibitor
Humans
Absorption

Orally available

Volume of distribution

Not Available

Protein binding

Not Available

Metabolism
Not Available
Route of elimination

Not Available

Half-life

Not Available

Clearance

Not Available

Adverse Effects
Improve decision support & research outcomes
With structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!
See the data
Improve decision support & research outcomes with our structured adverse effects data.
See a data sample
Toxicity

Not Available

Pathways
Not Available
Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
Not Available

Interactions

Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Not Available
Food Interactions
Not Available

Products

Drug product information from 10+ global regions
Our datasets provide approved product information including:
dosage, form, labeller, route of administration, and marketing period.
Access now
Access drug product information from over 10 global regions.
Access now
Product Ingredients
IngredientUNIICASInChI Key
Lucanthone hydrochloride918K9N56QZ548-57-2LAOOXBLMIJHMFO-UHFFFAOYSA-N
Active Moieties
NameKindUNIICASInChI Key
Hycanthoneprodrug2BXX5EVN2A3105-97-3MFZWMTSUNYWVBU-UHFFFAOYSA-N
International/Other Brands
Miracil D

Categories

Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This 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.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Thiochromenes
Sub Class
Not Available
Direct Parent
Thiochromenes
Alternative Parents
1-benzothiopyrans / Secondary alkylarylamines / Benzenoids / Vinylogous amides / Heteroaromatic compounds / Trialkylamines / Organopnictogen compounds / Organooxygen compounds / Organic oxides / Hydrocarbon derivatives
Substituents
1-benzothiopyran / Amine / Aromatic heteropolycyclic compound / Benzenoid / Benzothiopyran / Heteroaromatic compound / Hydrocarbon derivative / Organic nitrogen compound / Organic oxide / Organic oxygen compound
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
thioxanthenes (CHEBI:51052)
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
FC6D57000M
CAS number
479-50-5
InChI Key
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

References

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. [Article]
  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. [Article]
Human Metabolome Database
HMDB0015607
KEGG Compound
C11715
PubChem Compound
10180
PubChem Substance
46507260
ChemSpider
9772
BindingDB
50030282
ChEBI
51052
ChEMBL
CHEMBL279014
ZINC
ZINC000003831012
Therapeutic Targets Database
DAP001003
PharmGKB
PA164748783
Wikipedia
Lucanthone

Clinical Trials

Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
PhaseStatusPurposeConditionsCount
2TerminatedTreatmentGlioblastoma Multiforme (GBM)1
2WithdrawnTreatmentBrain Metastases / Non-Small Cell Lung Cancer (NSCLC)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.00315 mg/mLALOGPS
logP4.72ALOGPS
logP5.02Chemaxon
logS-5ALOGPS
pKa (Strongest Acidic)18.84Chemaxon
pKa (Strongest Basic)9.28Chemaxon
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 FiveNoChemaxon
Ghose FilterYesChemaxon
Veber's RuleYesChemaxon
MDDR-like RuleYesChemaxon
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)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSsplash10-0zi9-9052000000-539114a80db1e32eb9a2
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-00kf-0089000000-f3f83d8d424f42a254c7
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-000i-0009000000-cc884cf16f3ff50322dc
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-0gbc-4497000000-6351a349e23a1f583cfb
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-000i-0049000000-8f8d9b025e491b13cf2a
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-00di-9230000000-121d7e0a2ae44cc2cfdd
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-0006-0191000000-96bc5799f0f5d4caf65a
Predicted 1H NMR Spectrum1D NMRNot Applicable
Predicted 13C NMR Spectrum1D NMRNot Applicable
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-193.7808496
predicted
DarkChem Lite v0.1.0
[M-H]-193.5046496
predicted
DarkChem Lite v0.1.0
[M-H]-182.48445
predicted
DeepCCS 1.0 (2019)
[M+H]+193.8029496
predicted
DarkChem Lite v0.1.0
[M+H]+192.9144496
predicted
DarkChem Lite v0.1.0
[M+H]+184.84245
predicted
DeepCCS 1.0 (2019)
[M+Na]+193.4884496
predicted
DarkChem Lite v0.1.0
[M+Na]+193.4092496
predicted
DarkChem Lite v0.1.0
[M+Na]+190.93561
predicted
DeepCCS 1.0 (2019)

Targets

Build, predict & validate machine-learning models
Use our structured and evidence-based datasets to unlock new
insights and accelerate drug research.
Learn more
Use our structured and evidence-based datasets to unlock new insights and accelerate drug research.
Learn more
Details1. DNA topoisomerase 2-alpha
Kind
Protein
Organism
Humans
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 segr...
Gene Name
TOP2A
Uniprot ID
P11388
Uniprot Name
DNA topoisomerase 2-alpha
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. [Article]
  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. [Article]
  3. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
Details2. DNA-(apurinic or apyrimidinic site) lyase
Kind
Protein
Organism
Humans
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. Func...
Gene Name
APEX1
Uniprot ID
P27695
Uniprot Name
DNA-(apurinic or apyrimidinic site) lyase
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. [Article]
Details3. DNA
Kind
Nucleotide
Organism
Humans
Pharmacological action
Yes
Actions
Intercalation
DNA is the molecule of heredity, as it is responsible for the genetic propagation of most inherited traits. It is a polynucleic acid that carries genetic information on cell growth, division, and function. DNA consists of two long strands of nucleotides twisted into a double helix and held together by hydrogen bonds. The sequence of nucleotides determines hereditary characteristics. Each strand serves as the template for subsequent DNA replication and as a template for mRNA production, leading to protein synthesis via ribosomes.
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. [Article]
  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. [Article]
  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. [Article]
Details4. DNA topoisomerase 1
Kind
Protein
Organism
Humans
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 singl...
Gene Name
TOP1
Uniprot ID
P11387
Uniprot Name
DNA topoisomerase 1
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. [Article]
  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. [Article]

Drug created at October 21, 2007 22:23 / Updated at November 03, 2023 23:50