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Structure-activity relationship studies of ME1111, a novel antifungal agent for topical treatment of onychomycosis

The Journal of Antibiotics volume 78, pages 45–53 (2025)Cite this article

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Abstract

Onychomycosis is a prevalent disease in many areas of the world, affecting approximately 5.5% of the global population. Among several subtypes of onychomycosis, distal-lateral-subungual onychomycosis is the most common, and topical onychomycosis agents effective against this pathogenesis require properties such as high nail penetration and low affinity for keratin, the main component of the nail. To develop novel and highly effective antifungal agents with such properties, we first established an efficient ex vivo evaluation method using bovine hoof slices and human nails, and then used this method to screen an in-house compound library. Using this strategy, we identified 1, a structure with a phenyl-pyrazole skeleton. In subsequent analyses, we investigated the structure-activity relationship of 1, permitting the identification of 28 (Development Code ME1111).

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Acknowledgements

We thank Dr. Sojiro Shiokawa and Dr. Takeshi Furuuchi for encouragement and valuable comments in reviewing the manuscript during writing. We highly thank Dr. Takashi Murata for the instrumental analysis support of the compounds. We also thank Ms. Kazue Nagano and Ms. Kanako Mise for their technical assistance with the experiments. This study was supported by Meiji Seika Pharma Co., Ltd. (Tokyo, Japan).

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Authors and Affiliations

  1. Meiji Seika Pharma Co. Ltd, Chuo-ku, Tokyo, Japan

    Naomi Takei-Masuda, Maiko Iida, Makoto Ohyama, Kaori Kaneda & Yuji Tabata

  2. College of Bioresource Sciences, Nihon University, Kanagawa, Japan

    Kenji Ueda

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  1. Naomi Takei-Masuda
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  2. Maiko Iida
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  3. Makoto Ohyama
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Correspondence to Naomi Takei-Masuda.

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Takei-Masuda, N., Iida, M., Ohyama, M. et al. Structure-activity relationship studies of ME1111, a novel antifungal agent for topical treatment of onychomycosis. J Antibiot 78, 45–53 (2025). https://doi.org/10.1038/s41429-024-00789-1

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