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Review
. 2021;16(2):122-135.
doi: 10.2174/1574892816666210211090845.

Reposition of the Fungicide Ciclopirox for Cancer Treatment

Zhu Huang  1 , Shile Huang  2
Affiliations
Review

Reposition of the Fungicide Ciclopirox for Cancer Treatment

Zhu Huang et al. Recent Pat Anticancer Drug Discov. 2021.

Abstract

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.

Keywords: Apoptosis; angiogenesis; cell invasion; cell motility; cell proliferation; ciclopirox; fungicide; lymphangiogenesis; patent..

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Conflict of interest statement

Conflict of Interest

No potential conflicts of interest were disclosed.

Figures

Fig 1.
Fig 1.
Chemical structures of ciclopirox and its derivatives.
Fig 2.
Fig 2.
Ciclopirox inhibits multiple signaling molecules related to cancer development and progression.
Fig 3.
Fig 3.
Ciclopirox inhibits CDKs and activates ATR/Chk1, leading to cell cycle arrest at G1 phase.
Fig 4.
Fig 4.
Ciclopirox inhibits mTORC1 pathway.
Fig 5.
Fig 5.
Ciclopirox induces ROS leading to apoptosis or autophagy.
See this image and copyright information in PMC

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