Citation: Xin Chen, Linchong He, Xinhang Lv, Siying Liu, Jie Song, Jinrong Min, Pinghua Sun, Jian Li, Donglei Shi, Yunyuan Huang. WDR5-targeted activatable fluorescent probes for tumor-specific imaging in live cells and in vivo[J]. Chinese Chemical Letters, ;2026, 37(12): 112300. doi: 10.1016/j.cclet.2025.112300 shu

WDR5-targeted activatable fluorescent probes for tumor-specific imaging in live cells and in vivo

Xin Chen ^{a, 1,*,} ,
Linchong He ^{a, 1} ,
Xinhang Lv ^{c, 1} ,
Siying Liu ^b ,
Jie Song ^b ,
Jinrong Min ^b ,
Pinghua Sun ^{a, d} ,
Jian Li ^{c, d, e} ,
Donglei Shi ^{c, *,} ,
Yunyuan Huang ^{b, *,}

a.
State Key Laboratory of Bioactive Molecules and Druggability Assessment, College of Pharmacy, Jinan University, Guangzhou 510632, China
b.
Key Laboratory of Pesticide and Chemical Biology of Ministry of Education, Hubei Key Laboratory of Genetic Regulation and Integrative Biology, School of Life Sciences, Central China Normal University, Wuhan 430079, China
c.
Key Laboratory of Tropical Biological Resources of Ministry of Education and Hainan Engineering Research Center for Drug Screening and Evaluation, School of Pharmaceutical Sciences, Hainan University, Haikou 570228, China
d.
Institute for Safflower Industry Research, Key Laboratory of Xinjiang Phytomedicine Resource and Utilization (Ministry of Education), School of Pharmacy, Shihezi University, Shihezi 832003, China
e.
State Key Laboratory of Bioreactor Engineering, Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism, Frontiers Science Center for Materiobiology and Dynamic Chemistry, Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China

chenxin2023@jnu.edu.cn

dongleishi@hainanu.edu.cn

yunyuanhuang@ccnu.edu.cn

Received Date: 9 October 2025
Revised Date: 18 December 2025
Accepted Date: 19 December 2025
Available Online: 20 December 2025

Figures(5)

WD repeat domain 5 (WDR5), a WD40 repeat protein, promotes oncogenic processes in various human cancers through dynamic interactions with key partners such as the mixed lineage leukemia (MLL) complex and cellular Myc (c-Myc). Although small-molecule inhibitors targeting WDR5–protein interfaces hold therapeutic potential, the lack of specific molecular probes for real-time monitoring has limited the mechanistic investigation of WDR5 dynamics. Here, we report the rational design of P3, a first-in-class fluorescent probe derived from the WDR5 inhibitor OICR-9429 scaffold. Structural characterization via X-ray crystallography and surface plasmon resonance (SPR) confirmed micromolar binding affinity with WDR5, while systematic linker optimization elucidated structure–optical property relationships essential for bioimaging. P3 enabled in situ visualization of WDR5 distribution in cancer cells and facilitated tumor-selective intravital imaging in xenograft models. This probe offers high spatiotemporal resolution for tracking WDR5 pathobiology, directly linking its dysregulated localization to malignant progression through multimodal imaging validation.
- Epigenetic,
- WDR5,
- Fluorescent probe,
- Tumor targeting,
- Protein imaging
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沈阳化工大学材料科学与工程学院沈阳 110142