Unveiling the Therapeutic Potential of ATB1651: A Promising Topical Antifungal Agent for Onychomycosis

Unveiling the Therapeutic Potential of ATB1651: A Promising Topical Antifungal Agent for Onychomycosis

Na Hyun Lee1, Ji Won Choi2, Kyung-Tae Lee3, Siwon Kim2, Ye Rim Lee2, Hyeon Ji Kim2, Kyung Jin Seo3, Myung Ha Lee3, Bo Ko Jang1, Dong-Gi Lee1, Eunji Cheong3, Han-Seung Lee1, Yong-Sun Bahn2*, Ki Duk Park3*, Jong-Seung Lee1*

1AmtixBio Co., Ltd., Hanam-si, Gyeonggi-do, 12925, Republic of Korea

2Center for Brain Disorders, Brain Science Institute, Korea Institute of Science & Technology (KIST), Seoul, 02792, Republic of Korea

3Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul, 03722, Republic of Korea

*Email: jason_lee@amtixbio.com, ysbahn@yonsei.ac.kr, kdpark@kist.re.kr 

The escalating incidence of fungal diseases has underscored the need for effective treatments, given the limited antifungal drugs available. Recently, a novel compound 22h (ATB1651) with fungicidal properties and resistance evasion was developed. In this study, we confirmed that ATB1651 induces the alteration in fungal cell wall integrity, which is related to unfolded protein response (UPR), calcineurin, and Mpk1 MAPK pathways. For topical treatment application, we developed a formulation for topical delivery, and ATB1651 exerted significant antifungal efficacy in an ex vivo human nail infection model with Trichophyton rubrum. Following subcutaneous infection of mice with Candida albicans, ATB1651 effectively reduced the size of fungal infection lesions and improved the statements of the skin surface. To ensure the long-term toxicity of ATB1651 treatment, we performed in vivo toxicity studies. In conclusion, our findings suggest that ATB1651 is a promising novel antifungal drug that overcomes the limitations of current therapeutics.