Ajou University Research Team Achieves Breakthrough in Autoimmune Disease Therapeutics Development

Offering Hope for Overcoming Intractable Diseases

Ajou University announced on September 10 that the research team led by Professors Kim Wook and Choi Sangdon from the Department of Molecular Science and Technology at the College of Advanced Bio-Convergence and Graduate School has successfully developed novel small-molecule compounds that selectively inhibit the excessive activation of endosomal Toll-like receptors, which are known as a major cause of autoimmune diseases.

As a result, these compounds are expected to present a new paradigm as next-generation oral therapeutics for autoimmune diseases, offering high stability and functionality.

This research was published online on September 1 in the renowned journal , which is part of the Nature Portfolio, under the title "Discovery of ETI41 and ETI60: Novel Selective Endosomal Toll-Like Receptor Inhibitors for the Treatment of Autoimmune Diseases."

This study also involved Professor Seo Changhee from the Department of Medicine (Division of Rheumatology) and Professor Kim Moonseok from the Department of Applied Chemistry at Ajou University. Doctor Jeong Euisuk and Doctor Lee Wanghee from the Graduate School's Department of Molecular Science and Technology played leading roles in experiments and analysis as first authors. The new drug development company SNK Therapeutics, led by CEO Choi Sangdon, also participated in the research.

Research image. Ajou University

Autoimmune diseases, which occur when the body's immune system attacks its own tissues beyond its original defensive function, have unclear causes and a wide variety of symptoms and affected areas. As a result, they are among the most difficult-to-treat diseases, following cancer and cardiovascular diseases, with a large number of patients suffering from them. Representative autoimmune diseases include rheumatoid arthritis, type 1 diabetes, systemic lupus erythematosus, psoriasis, and inflammatory bowel diseases such as Crohn's disease.

Treatment for autoimmune diseases involves suppressing the excessively activated immune response to reduce the immune system's overreaction. However, existing treatments work by broadly suppressing the entire immune system, which inevitably exposes patients to several side effects, such as ▲increased risk of infection and ▲exposure to long-term toxicity. Furthermore, many of these treatments require expensive injectable drugs, placing a financial and logistical burden on patients who must visit hospitals for treatment. Therefore, there has been a need to develop oral therapeutics that improve patient convenience, reduce costs, and offer both stability and functionality.

The Ajou University research team sought to overcome these challenges by focusing on the signaling pathways of endosomal Toll-like receptors (TLRs), which play a key role in the onset of autoimmune diseases. Endosomal TLRs 3, 7, 8, and 9 are located within intracellular organelles and recognize pathogen-derived nucleic acids to trigger a strong immune response. However, when excessively activated, they can lead to chronic autoimmune diseases. Based on this, the team adopted a differentiated approach from existing treatments.

The researchers synthesized various derivatives using a structure-activity relationship (SAR)-based drug design method utilizing artificial intelligence computing, and through this process, they discovered a candidate compound called ETI15. They then optimized the molecular structure of the candidate compound and successfully developed ETI41 (Endosomal TLR Inhibitor 41) and ETI60 (Endosomal TLR Inhibitor 60).

Research image. Ajou University

Professor Kim Wook, who led the research, explained, "Unlike conventional immunosuppressants, the two compounds developed in this study are the world's first candidates that selectively inhibit the overactivation of endosomal TLRs rather than suppressing the entire immune response. They offer several advantages in terms of treatment efficiency, safety, and convenience for autoimmune diseases."

The research team plans to expand the application of these compounds to various refractory autoimmune diseases such as rheumatoid arthritis, inflammatory bowel disease, and cardiovascular inflammatory diseases through follow-up studies, and ultimately aims to develop a global new drug.

Meanwhile, this research was supported by the Basic Research Program (Global Research Laboratory Program and Mid-Career Researcher Program) of the National Research Foundation of Korea and the Gyeonggi Regional Research Center (GRRC) program. Patent applications and technology transfer have been completed, and preclinical studies have concluded. Currently, follow-up clinical development is underway, focusing on ETI41.

This content was produced with the assistance of AI translation services.