Drug Information

Drug (ID: DG00863) and It's Reported Resistant Information

• Name: Lucanthone
• Synonyms: LUCANTHONE; 479-50-5; Lucanthon; Lucanthonum; Lucantona; Lucanthonum [INN-Latin]; Lucantona [INN-Spanish]; 1-((2-(Diethylamino)ethyl)amino)-4-methylthioxanthen-9-one; 1-{[2-(Diethylamino)ethyl]amino}-4-methyl-9H-thioxanthen-9-one; UNII-FC6D57000M; CHEBI:51052; 1-((2-(diethylamino)ethyl)amino)-4-methyl-9H-thioxanthen-9-one; FC6D57000M; Lucanthone [INN:BAN]; 1-[[2-(Diethylamino)ethyl]amino]-4-methylthioxanthone; 1-diethylaminoethylethylamino-4-methyl-thioxanthenone; 1-{[2-(diethylamino)ethyl]amino}-4-methylthioxanthen-9-one; NSC14574; CCRIS 1106; EINECS 207-532-4; BRN 0312369; AI3-16160; NCIMech_000830; SCHEMBL9156; 5-18-11-00503 (Beilstein Handbook Reference); CHEMBL279014; DTXSID6023230; HY-B2098; Thioxanthen-9-one, 1-((2-(diethylamino)ethyl)amino)-4-methyl-; ZINC3831012; 9H-Thioxanthen-9-one, 1-[[2-(diethylamino)ethyl]amino]-4-methyl-; BDBM50030282; CCG-35817; s6471; CS-6665; DB04967; BS-49111; NCI60_000988; 479L505; Q6696022; 1-(2-diethylaminoethylamino)-4-methyl-thioxanthen-9-one; 1-[2-(diethylamino)ethylamino]-4-methylthioxanthen-9-one; 9H-Thioxanthen-9-one, 1-((2-(diethylamino)ethyl)amino)-4-methyl- (9CI)
• Indication:
  In total 1 Indication(s)
  Solid tumour/cancer [ICD-11: 2A00-2F9Z]; Approved; [1]
• Target: DNA topoisomerase II (TOP2); TOP2A_HUMAN TOP2B_HUMAN; [1]
• Formula: C20H24N2OS
• IsoSMILES: CCN(CC)CCNC1=C2C(=C(C=C1)C)SC3=CC=CC=C3C2=O
• 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
• InChIKey: FBQPGGIHOFZRGH-UHFFFAOYSA-N
• PubChem CID: 10180
• ChEBI ID: CHEBI:51052
• TTD Drug ID: D09OZC
• DrugBank ID: DB04967

Type(s) of Resistant Mechanism of This Drug

  ADTT: Aberration of the Drug's Therapeutic Target

Drug Resistance Data Categorized by Their Corresponding Diseases

ICD-02: Benign/in-situ/malignant neoplasm

Brain cancer [ICD-11: 2A00]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Palmitoyl-protein thioesterase 1 (PPT1) [2]

• Sensitive Disease: Glioma [ICD-11: 2A00.1]
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Luciferase+ GL261 cells; N.A.; Homo sapiens (Human); N.A.
• In Vitro Model: GBM43 cells; Brain; Homo sapiens (Human); CVCL_E5GD
• In Vitro Model: GBM9 cells; Brain; Homo sapiens (Human); N.A.
• In Vivo Model: C57/Bl6 mice modle; Murine glioma model; Mus musculus
• Experiment for Molecule Alteration: Immunohistochemistry; Western blot assay; Molecular docking assay
• Mechanism Description: Lucanthone efficiently abates stemness in patient-derived GSC and reduces tumor microtube formation in GSC, an emerging hallmark of treatment resistance in GBM. In glioma tumors derived from cells with acquired resistance to TMZ, lucanthone retains the ability to perturb tumor growth, inhibits autophagy by targeting lysosomes, and reduces Olig2 positivity. We also find that lucanthone may act as an inhibitor of palmitoyl protein thioesterase 1. Our results suggest that lucanthone may function as a potential treatment option for GBM tumors that are not amenable to TMZ treatment. SIGNIFICANCE STATEMENT: We report that the antischistosome agent lucanthone impedes tumor growth in a preclinical model of temozolomide-resistant glioblastoma and reduces the numbers of stem-like glioma cells. In addition, it acts as an autophagy inhibitor, and its mechanism of action may be via inhibition of palmitoyl protein thioesterase 1. As there are no defined therapies approved for recurrent, TMZ-resistant tumor, lucanthone could emerge as a treatment for glioblastoma tumors that may not be amenable to TMZ both in the newly diagnosed and recurrent settings.

References

• Ref 1: Quinolizidine-Derived Lucanthone and Amitriptyline Analogues Endowed with Potent Antileishmanial Activity .Pharmaceuticals (Basel). 2020 Oct 25;13(11):339. doi: 10.3390/ph13110339. 10.3390/ph13110339
• Ref 2: Lucanthone, a Potential PPT1 Inhibitor, Perturbs Stemness, Reduces Tumor Microtube Formation, and Slows the Growth of Temozolomide-Resistant Gliomas In Vivo. J Pharmacol Exp Ther. 2024 Mar 15;389(1):51-60.