Optimisation and mechanistic characterization of a selective benzoxazine-based MAP4K4 inhibitor in pancreatic cancer cells
values of 4.41-4.65 μM and 4.03-5.12 μM, respectively. F389-0736 also inhibited clonogenic growth and induced sub-G1 accumulation with activation of apoptotic signalling. RNA sequencing identified 398 differentially expressed genes and revealed enrichment of inflammatory and stress response pathways, programmed cell death programs, oncogenic signalling perturbation, and metabolic reprogramming. These findings identify F389-0736 as a potent and selective benzoxazine-based MAP4K4 inhibitor and support its use as a chemical probe and lead scaffold for investigating MAP4K4-dependent signalling and therapeutic vulnerability in pancreatic cancer.
Authors
- Jung-Chun Chu (ORCID: https://orcid.org/0009-0007-5809-5857)
- Jui‐Hua Hsieh (ORCID: https://orcid.org/0000-0003-1620-1571)
- Shih‐Chung Yen (ORCID: https://orcid.org/0000-0001-8596-0083)
- Kai‐Cheng Hsu (ORCID: https://orcid.org/0000-0002-9022-6673)
- Yun‐Hsuan Yeh (ORCID: https://orcid.org/0000-0002-8983-6300)
- Yi-Wen Wu (ORCID: https://orcid.org/0000-0002-6625-0630)
- Cheng-Ying Chu (ORCID: https://orcid.org/0000-0003-1002-8640)
- Tzu-Ying Sung
- Yu-Ting Fang-Chin (ORCID: https://orcid.org/0009-0002-0634-7104)
- Shiow-Lin Pan
- TONY EIGHT LIN
- Sing-Han Huang
- Chun-Lin Yang
- Bor-Jiun Chen
- Kai-Chien Yang
Institutions
- National Institutes of Health (US)
- National Taiwan University (TW)
- Chinese University of Hong Kong (HK)
- National Institute of Environmental Health Sciences (US)
- Chinese University of Hong Kong, Shenzhen (CN)
- Wan Fang Hospital (TW)
- Taipei Medical University (TW)
Publication Details
- Journal
- Journal of Enzyme Inhibition and Medicinal Chemistry
- Published
- 2026-10-16
- DOI
- https://doi.org/10.1080/14756366.2026.2743434
- Primary Topic
- Pancreatic and Hepatic Oncology Research
- Type
- article
- Field-Weighted Citation Impact
- 0.00