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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
Structure for Lucanthone (DB04967)
- 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
Pharmacology
- Indication
Intended for use as a radiation sensitizer in the treatment of brain cancer.
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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.
Target Actions Organism ADNA topoisomerase 2-alpha inhibitorHumans ADNA topoisomerase 2-beta inhibitorHumans ADNA repair nuclease/redox regulator APEX1 inhibitorHumans ADNA intercalationHumans ADNA topoisomerase 1 inhibitorHumans - 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
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Not Available
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- 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
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Ingredient UNII CAS InChI Key Lucanthone hydrochloride 918K9N56QZ 548-57-2 LAOOXBLMIJHMFO-UHFFFAOYSA-N - Active Moieties
Name Kind UNII CAS InChI Key Hycanthone prodrug 2BXX5EVN2A 3105-97-3 MFZWMTSUNYWVBU-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
- 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]
- 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]
- External Links
- 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
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package Phase Status Purpose Conditions Count Start Date Why Stopped 100+ additional columns Unlock 175K+ rows when you subscribe.View sample data2 Terminated Treatment Glioblastoma Multiforme (GBM) 1 somestatus stop reason just information to hide 2 Withdrawn Treatment Brain Metastases / Non-Small Cell Lung Cancer (NSCLC) 1 somestatus stop reason just information to hide
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
Property Value Source Water Solubility 0.00315 mg/mL ALOGPS logP 4.72 ALOGPS logP 5.02 Chemaxon logS -5 ALOGPS pKa (Strongest Acidic) 18.84 Chemaxon pKa (Strongest Basic) 9.28 Chemaxon Physiological Charge 1 Chemaxon Hydrogen Acceptor Count 3 Chemaxon Hydrogen Donor Count 1 Chemaxon Polar Surface Area 32.34 Å2 Chemaxon Rotatable Bond Count 6 Chemaxon Refractivity 106.01 m3·mol-1 Chemaxon Polarizability 39.6 Å3 Chemaxon Number of Rings 3 Chemaxon Bioavailability 1 Chemaxon Rule of Five No Chemaxon Ghose Filter Yes Chemaxon Veber's Rule Yes Chemaxon MDDR-like Rule Yes Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.9644 Blood Brain Barrier + 0.9538 Caco-2 permeable + 0.5555 P-glycoprotein substrate Substrate 0.8992 P-glycoprotein inhibitor I Inhibitor 0.62 P-glycoprotein inhibitor II Non-inhibitor 0.7254 Renal organic cation transporter Non-inhibitor 0.5391 CYP450 2C9 substrate Non-substrate 0.6567 CYP450 2D6 substrate Substrate 0.545 CYP450 3A4 substrate Substrate 0.5259 CYP450 1A2 substrate Inhibitor 0.8476 CYP450 2C9 inhibitor Non-inhibitor 0.8837 CYP450 2D6 inhibitor Inhibitor 0.704 CYP450 2C19 inhibitor Non-inhibitor 0.7842 CYP450 3A4 inhibitor Non-inhibitor 0.5884 CYP450 inhibitory promiscuity High CYP Inhibitory Promiscuity 0.6989 Ames test AMES toxic 0.9107 Carcinogenicity Non-carcinogens 0.761 Biodegradation Not ready biodegradable 1.0 Rat acute toxicity 2.5482 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.6183 hERG inhibition (predictor II) Inhibitor 0.8499
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted GC-MS Spectrum - GC-MS Predicted GC-MS splash10-0zi9-9052000000-539114a80db1e32eb9a2 Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-00kf-0089000000-f3f83d8d424f42a254c7 Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-000i-0009000000-cc884cf16f3ff50322dc Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-0gbc-4497000000-6351a349e23a1f583cfb Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-000i-0049000000-8f8d9b025e491b13cf2a Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-00di-9230000000-121d7e0a2ae44cc2cfdd Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-0006-0191000000-96bc5799f0f5d4caf65a Predicted 1H NMR Spectrum 1D NMR Not Applicable Predicted 13C NMR Spectrum 1D NMR Not Applicable - Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 193.7808496 predictedDarkChem Lite v0.1.0 [M-H]- 193.5046496 predictedDarkChem Lite v0.1.0 [M-H]- 182.48445 predictedDeepCCS 1.0 (2019) [M+H]+ 193.8029496 predictedDarkChem Lite v0.1.0 [M+H]+ 192.9144496 predictedDarkChem Lite v0.1.0 [M+H]+ 184.84245 predictedDeepCCS 1.0 (2019) [M+Na]+ 193.4884496 predictedDarkChem Lite v0.1.0 [M+Na]+ 193.4092496 predictedDarkChem Lite v0.1.0 [M+Na]+ 190.93561 predictedDeepCCS 1.0 (2019)
Targets
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- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Key decatenating enzyme that alters DNA topology by binding to two double-stranded DNA molecules, generating a double-stranded break in one of the strands, passing the intact strand through the broken strand, and religating the broken strand (PubMed:17567603, PubMed:18790802, PubMed:22013166, PubMed:22323612). May play a role in regulating the period length of BMAL1 transcriptional oscillation (By similarity)
- Specific Function
- ATP binding
- Gene Name
- TOP2A
- Uniprot ID
- P11388
- Uniprot Name
- DNA topoisomerase 2-alpha
- Molecular Weight
- 174383.88 Da
References
- 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]
- 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]
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
- Zhou Y, Zhang Y, Zhao D, Yu X, Shen X, Zhou Y, Wang S, Qiu Y, Chen Y, Zhu F: TTD: Therapeutic Target Database describing target druggability information. Nucleic Acids Res. 2024 Jan 5;52(D1):D1465-D1477. doi: 10.1093/nar/gkad751. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Key decatenating enzyme that alters DNA topology by binding to two double-stranded DNA molecules, generating a double-stranded break in one of the strands, passing the intact strand through the broken strand, and religating the broken strand. Plays a role in B-cell differentiation
- Specific Function
- ATP binding
- Gene Name
- TOP2B
- Uniprot ID
- Q02880
- Uniprot Name
- DNA topoisomerase 2-beta
- Molecular Weight
- 183265.825 Da
References
- Zhou Y, Zhang Y, Zhao D, Yu X, Shen X, Zhou Y, Wang S, Qiu Y, Chen Y, Zhu F: TTD: Therapeutic Target Database describing target druggability information. Nucleic Acids Res. 2024 Jan 5;52(D1):D1465-D1477. doi: 10.1093/nar/gkad751. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Multifunctional protein that plays a central role in the cellular response to oxidative stress. The two major activities of APEX1 are DNA repair and redox regulation of transcriptional factors. Functions as an 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 by catalyzing hydrolytic incision of the phosphodiester backbone immediately adjacent to the damage, generating a single-strand break with 5'-deoxyribose phosphate and 3'-hydroxyl ends. Also incises at AP sites in the DNA strand of DNA/RNA hybrids, single-stranded DNA regions of R-loop structures, and single-stranded RNA molecules. Has 3'-5' exoribonuclease activity on mismatched deoxyribonucleotides at the 3' termini of nicked or gapped DNA molecules during short-patch BER. Possesses DNA 3' phosphodiesterase activity capable of removing lesions (such as phosphoglycolate) blocking the 3' side of DNA strand breaks. May also play a role in the epigenetic regulation of gene expression by participating in DNA demethylation. Acts as a loading factor for POLB onto non-incised AP sites in DNA and stimulates the 5'-terminal deoxyribose 5'-phosphate (dRp) excision activity of POLB. Plays a role in protection from granzyme-mediated cellular repair leading to cell death. Also involved in the DNA cleavage step of class switch recombination (CSR). On the other hand, APEX1 also exerts reversible nuclear redox activity to regulate DNA binding affinity and transcriptional activity of transcriptional factors by controlling the redox status of their DNA-binding domain, such as the FOS/JUN AP-1 complex after exposure to IR. Involved in calcium-dependent down-regulation of parathyroid hormone (PTH) expression by binding to negative calcium response elements (nCaREs). Together with HNRNPL or the dimer XRCC5/XRCC6, associates with nCaRE, acting as an activator of transcriptional repression. Stimulates the YBX1-mediated MDR1 promoter activity, when acetylated at Lys-6 and Lys-7, leading to drug resistance. Acts also as an endoribonuclease involved in the control of single-stranded RNA metabolism. Plays a role in regulating MYC mRNA turnover by preferentially cleaving in between UA and CA dinucleotides of the MYC coding region determinant (CRD). In association with NMD1, plays a role in the rRNA quality control process during cell cycle progression. Associates, together with YBX1, on the MDR1 promoter. Together with NPM1, associates with rRNA. Binds DNA and RNA
- Specific Function
- 3'-5' exonuclease activity
- Gene Name
- APEX1
- Uniprot ID
- P27695
- Uniprot Name
- DNA repair nuclease/redox regulator APEX1
- Molecular Weight
- 35554.165 Da
References
- 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]
Yes
Intercalation
References
- 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]
- 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]
- 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]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General 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'-phosphotyrosyl)-enzyme intermediate and the expulsion of a 5'-OH DNA strand. The free DNA strand then rotates around the intact phosphodiester bond on the opposing strand, thus removing DNA supercoils. Finally, in the religation step, the DNA 5'-OH attacks the covalent intermediate to expel the active-site tyrosine and restore the DNA phosphodiester backbone (By similarity). Regulates the alternative splicing of tissue factor (F3) pre-mRNA in endothelial cells. Involved in the circadian transcription of the core circadian clock component BMAL1 by altering the chromatin structure around the ROR response elements (ROREs) on the BMAL1 promoter
- Specific Function
- ATP binding
- Gene Name
- TOP1
- Uniprot ID
- P11387
- Uniprot Name
- DNA topoisomerase 1
- Molecular Weight
- 90725.19 Da
References
- 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]
- 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 October 10, 2024 16:44