2. Academic Validation
  3. KB-0118, A novel BET bromodomain inhibitor, suppresses Th17-mediated inflammation in inflammatory bowel disease

KB-0118, A novel BET bromodomain inhibitor, suppresses Th17-mediated inflammation in inflammatory bowel disease

  • Biomed Pharmacother. 2025 Apr:185:117933. doi: 10.1016/j.biopha.2025.117933.
Yeo-Jin Jeong 1,  Yeon-Su Ok 2,  Gi-Nam Kwon 2,  Min-Young Kim 3,  Jin Hong Chun 3,  Sukmo Kang 3,  Haemi Yang 4,  Minhee Son 4,  In-Hyun Lee 4,  Gi-Cheon Kim 5,  Ho-Keun Kwon 6
Affiliations

Affiliations

  • 1 Department of Microbiology and Immunology, Yonsei University College of Medicine, Seoul 03722, Republic of Korea; Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine, Seoul, Republic of Korea.
  • 2 Department of Microbiology and Immunology, Yonsei University College of Medicine, Seoul 03722, Republic of Korea.
  • 3 Keyfron Bio Co., Ltd., Cheongju-si, Chungcheongbuk-do 28115, Republic of Korea.
  • 4 Benobio Co., Ltd., Seongnam-si, Gyeonggi-do 13494, Republic of Korea.
  • 5 Department of Microbiology and Immunology, Yonsei University College of Medicine, Seoul 03722, Republic of Korea. Electronic address: KIMGC35@yuhs.ac.
  • 6 Department of Microbiology and Immunology, Yonsei University College of Medicine, Seoul 03722, Republic of Korea; Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine, Seoul, Republic of Korea; Institute for Immunology and Immunological Diseases, Yonsei University College of Medicine, Seoul 03722, Republic of Korea; Pohang University of Science and Technology, Pohang 37673, Republic of Korea. Electronic address: HK@yuhs.ac.
PMID: 40088776 DOI: 10.1016/j.biopha.2025.117933
Abstract

Inflammatory bowel disease (IBD) presents complex pathologies and remains challenging to treat, highlighting the urgent need for innovative therapeutics. This study evaluates KB-0118, a novel BET bromodomain inhibitor targeting BRD4, for its immunomodulatory effects in IBD. KB-0118 effectively inhibited pro-inflammatory cytokines, including TNF, IL-1β, and IL-23a, and selectively suppressed Th17 cell differentiation, a critical driver of IBD pathology. In both DSS-induced and T cell-mediated colitis models, KB-0118 significantly reduced disease severity, preserved colon structure, and lowered IL-17 expression. Mechanistic studies suggest KB-0118's modulation of Th17-driven inflammation occurs through epigenetic suppression of BRD4, confirmed by transcriptomic analysis showing downregulation of STAT3 and BRD4 target genes. Compared to standard BET inhibitors like JQ1 and MS402, KB-0118 exhibited enhanced efficacy in restoring immune balance in IBD, positioning it as a promising therapeutic candidate for chronic inflammatory diseases. Further investigation into KB-0118's specificity and long-term effects will be essential to clarify its full clinical potential.

Keywords

BET Bromodomain inhibitor; Inflammatory bowel disease; KB-0118; T helper 17 cells.

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