Recent patents on anti-cancer drug discovery · 2021
Reposition of the Fungicide Ciclopirox for Cancer Treatment.
СтатьяОбзорНазвание и аннотация: Перевод в очереди
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Huang Zhu, Huang Shile
Аннотация
BACKGROUND: Ciclopirox (CPX), a broad-spectrum fungicide, has been widely used to treat fungal infection on the skin and nails for decades. Recent preclinical and clinical studies have shown that CPX also possesses promising anticancer activity.
OBJECTIVE: The objective of this study is to summarize the patents, the pharmacological and toxicological properties, the anticancer activity, and the mechanisms of action of CPX and its derivatives as anticancer agents.
METHODS: PubMed and Google using the keywords "ciclopirox", "cancer or tumor" and "patent" were searched, and the identified literature was reviewed.
RESULTS: Pharmacological and toxicological profiles from preclinical and clinical studies support that systemic administration of CPX and its derivatives is feasible and safe for cancer treatment. CPX exerts its anticancer activity by inhibiting cell proliferation, inducing apoptosis, suppressing cell migration and invasion, and inhibiting angiogenesis and lymphangiogenesis. Mechanistically, CPX impacts the expression or activities of multiple signaling molecules or pathways, such as ribonucleotide reductase, Myc, DJ-1, Wnt/β-catenin, DOHH/eIF5A/PEAK1, VEGFR-3/ERK1/2, ATR/Chk1/Cdc25A, and AMPK/TSC/mTORC1. Most of these effects are attributed to iron chelation by CPX. Five patents have been retrieved: four patents on the development of CPX prodrugs to improve the water solubility and bioavailability of CPX, and one patent on the methods of bladder cancer treatment with CPX, CPX-O, or a CPX prodrug.
CONCLUSION: CPX has a great potential to be repositioned for cancer therapy.
OBJECTIVE: The objective of this study is to summarize the patents, the pharmacological and toxicological properties, the anticancer activity, and the mechanisms of action of CPX and its derivatives as anticancer agents.
METHODS: PubMed and Google using the keywords "ciclopirox", "cancer or tumor" and "patent" were searched, and the identified literature was reviewed.
RESULTS: Pharmacological and toxicological profiles from preclinical and clinical studies support that systemic administration of CPX and its derivatives is feasible and safe for cancer treatment. CPX exerts its anticancer activity by inhibiting cell proliferation, inducing apoptosis, suppressing cell migration and invasion, and inhibiting angiogenesis and lymphangiogenesis. Mechanistically, CPX impacts the expression or activities of multiple signaling molecules or pathways, such as ribonucleotide reductase, Myc, DJ-1, Wnt/β-catenin, DOHH/eIF5A/PEAK1, VEGFR-3/ERK1/2, ATR/Chk1/Cdc25A, and AMPK/TSC/mTORC1. Most of these effects are attributed to iron chelation by CPX. Five patents have been retrieved: four patents on the development of CPX prodrugs to improve the water solubility and bioavailability of CPX, and one patent on the methods of bladder cancer treatment with CPX, CPX-O, or a CPX prodrug.
CONCLUSION: CPX has a great potential to be repositioned for cancer therapy.