Liver fibrosis is one of the diseases for which the development of a treatment is urgently needed. Currently, there is only one treatment approved by the Food and Drug Administration (FDA), and its effectiveness is limited. In this situation, domestic researchers have proposed a solution by developing a new drug candidate '19c'.
Professor Ahn Jin-hee of the Gwangju Institute of Science and Technology (GIST), who is also the CEO of JD BioScience, and Professor Kim Ha-il of the Korea Advanced Institute of Science and Technology (KAIST) announced on the 20th that their joint research team has developed a new drug candidate for the treatment of liver fibrosis. The research results were published in the international journal "Journal of Medicinal Chemistry" on the 6th.
Liver fibrosis is a disease characterized by the excessive accumulation of extracellular matrix (ECM) in the liver due to cellular damage, leading to a disruption of liver structure and function. The extracellular matrix is a network of proteins and polysaccharides that exist outside the cells. Major causes include long-term alcohol abuse, metabolic diseases resulting from obesity, autoimmune liver diseases, and viral hepatitis. As liver fibrosis progresses, it can develop into cirrhosis or liver cancer, making early treatment essential.
However, as of now, the only FDA-approved treatment for liver fibrosis is 'Resmetirom'. Resmetirom shows a limited improvement of 12-14% compared to a placebo. Therefore, there is an urgent need for the development of new therapies that preserve and improve liver structure and function using new mechanisms.
The research team discovered a substance '19c' that suppresses the expression of proteins related to fibrosis and significantly reduces the accumulation of extracellular matrix in animal models of liver fibrosis. '19c' effectively halts the progression of fibrosis by blocking the action of serotonin receptor 2B (HTR2B) in the 'hepatic stellate cells' present in the liver.
The research team also minimized potential side effects that '19c' may cause. While serotonin is known to be a neurotransmitter that conveys feelings of happiness and satisfaction in the central nervous system, inhibiting the 5HT2B receptor can result in side effects such as attention deficits or impulsivity. Thus, to protect the brain, '19c' was designed to be selectively permeable through the blood-brain barrier, which reduces potential side effects on the central nervous system.
Professor Ahn Jin-hee noted, "The '19c' developed through this research is expected to set a new milestone in the development of liver fibrosis treatments, possessing powerful anti-fibrotic efficacy and safety simultaneously," and added, "If safety and efficacy are proven in future clinical studies, it has a high potential to evolve into a practical treatment."
References
Journal of Medicinal Chemistry (2025), DOI: https://doi.org/10.1021/acs.jmedchem.4c03003