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Updated: May 7, 2026
Assessing Specificity of Anticancer Drugs In Vitro
Published on: March 23, 2016
Repurposing FDA-approved drugs targeting FZD10 in nasopharyngeal carcinoma: insights from molecular dynamics
Chawalit Ngernsombat1,2, Utid Suriya3, Pongphol Prattapong1,3
1Graduate Program in Molecular Medicine, Faculty of Science, Mahidol University, Bangkok, 10400, Thailand.
Abstract:
Wnt signaling is a critical pathway implicated in cancer development, with Frizzled proteins, particularly FZD10, playing key roles in tumorigenesis and recurrence. This study focuses on the potential of repurposed FDA-approved drugs targeting FZD10 as a therapeutic strategy for nasopharyngeal carcinoma (NPC). The tertiary structure of human FZD10 was constructed using homology modeling, validated by Ramachandran plot and ProQ analysis. Virtual screening of 1,094 FDA-approved drugs identified 17 potential inhibitors, with prazosin, rilpivirine, doxazosin, and nicergoline demonstrating significant cytotoxicity against NPC cells. Further molecular dynamics simulations and binding energy analyses confirmed the stable binding of these drugs to FZD10. The results suggest that these repurposed drugs could serve as promising candidates for targeted NPC therapy, warranting further investigation.
Insights
Repurposed drugs targeting Frizzled 10 (FZD10) show promise for nasopharyngeal carcinoma (NPC) therapy. Prazosin, rilpivirine, doxazosin, and nicergoline effectively reduced NPC cell growth in preclinical studies.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Wnt signaling pathway deregulation is crucial in cancer development.
- Frizzled 10 (FZD10) is implicated in nasopharyngeal carcinoma (NPC) tumorigenesis and recurrence.
- Targeting FZD10 presents a potential therapeutic avenue for NPC.
Purpose of the Study:
- To identify FDA-approved drugs that can target FZD10 for NPC treatment.
- To evaluate the efficacy of repurposed drugs against NPC cells.
- To confirm the binding affinity and stability of identified drug candidates to FZD10.
Main Methods:
- Homology modeling was used to construct the tertiary structure of human FZD10.
- Virtual screening of 1,094 FDA-approved drugs was performed.
- Molecular dynamics simulations and binding energy analyses were conducted to validate drug-target interactions.
Main Results:
- Seventeen potential FZD10 inhibitors were identified from the virtual screen.
- Prazosin, rilpivirine, doxazosin, and nicergoline exhibited significant cytotoxicity against NPC cells.
- These drugs demonstrated stable binding to FZD10, confirmed by computational analyses.
Conclusions:
- Repurposed FDA-approved drugs, including prazosin, rilpivirine, doxazosin, and nicergoline, are potential therapeutic candidates for NPC.
- Targeting FZD10 with these repurposed agents warrants further clinical investigation for NPC treatment.
- This study highlights the potential of drug repurposing in developing novel cancer therapies.
