Discovery of ATB1651, a Novel Antifungal Agent with Broad-Spectrum Activity against Fungal Pathogens

Discovery of ATB1651, a Novel Antifungal Agent with Broad-Spectrum Activity against Fungal Pathogens

Bo Ko Jang1, Ji Won Choi2, Kyung-Tae Lee3, Siwon Kim2, Ye Rim Lee2, Hyeon Ji Kim2, Kyung Jin Seo3, Na Hyun Lee1, Dong-Gi Lee1, Han-Seung Lee1, Yong-Sun Bahn2*, and 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 prevalence of fungal infectious diseases has exhibited a marked escalation in recent times, constituting a substantial peril to public health. The prevailing pharmacotherapeutic arsenal for fungal infections is hamstrung by intrinsic limitations encompassing hepatorenal toxicity, fungistatic attributes, and drug resistance. This highlights the importance of developing new antifungal agents that are more effective and cause fewer adverse effects. We conducted an initial screening to assess antifungal activity against C. neoformans using an in-house library, yielding two promising compounds (HIT1 and HIT2). To improve the antifungal efficacy and drug-like properties, we optimized compounds by substituting the aryl ring, alkyl chain, or methyl groups. Compound 22h (ATB1651) showed broad-spectrum antifungal activity for diverse fungal pathogens. In addition, ATB1651 exhibited fungicidal, synergetic effects with clinically available drugs and no resistance against various fungi. Overall, we propose that the newly developed compound ATB1651, with its broad-spectrum activity and excellent antifungal properties against various fungal pathogens, holds promise as a novel therapeutic agent.