2. Academic Validation
  3. Identification of new small molecule inhibitors of PD-1/PD-L1 interaction by a comprehensive ligand fishing system

Identification of new small molecule inhibitors of PD-1/PD-L1 interaction by a comprehensive ligand fishing system

  • J Pharm Biomed Anal. 2025 Nov 23:270:117281. doi: 10.1016/j.jpba.2025.117281.
Dongyao Wang 1,  Ying Zhang 2,  Dan Li 3,  Ningqi Xia 2,  Xiaofei Wang 2,  Xiaofei Chen 4,  Bin Lu 2,  Diya Lv 5,  Yan Cao 6
Affiliations

Affiliations

  • 1 Department of Pharmaceutical Analysis, School of Pharmacy, Naval Medical University, Shanghai 200433, China; Shanghai Key Laboratory for Pharmaceutical Metabolite Research, School of Pharmacy, Naval Medical University, Shanghai 200433, China.
  • 2 Department of Biochemical Pharmacy, School of Pharmacy, Naval Medical University, Shanghai 200433, China.
  • 3 Eastern Hepatobiliary Surgery Institute, Naval Medical University, Shanghai 200433, China.
  • 4 Center for Instrumental Analysis, School of Pharmacy, Naval Medical University, Shanghai 200433, China.
  • 5 Center for Instrumental Analysis, School of Pharmacy, Naval Medical University, Shanghai 200433, China. Electronic address: [email protected].
  • 6 Department of Biochemical Pharmacy, School of Pharmacy, Naval Medical University, Shanghai 200433, China; Shanghai Key Laboratory for Pharmaceutical Metabolite Research, School of Pharmacy, Naval Medical University, Shanghai 200433, China. Electronic address: [email protected].
PMID: 41308584 DOI: 10.1016/j.jpba.2025.117281
Abstract

The development of programmed death 1 (PD-1) checkpoint/programmed death-ligand 1 (PD-L1) interaction inhibitors has opened a new front in the treatment of carcinoma. An increasing amount of research is devoted to small-molecule compounds that target this PD-1/PD-L1 interaction. In this article, we report the discovery of three new PD-1/PD-L1 inhibitors from Scutellaria baicalensis Georgi and Sophora flavescens Aiton herbal extracts, namely baicalin, maackiain, and oxysophocarpine, using a comprehensive ligand fishing system, which integrates a dual-target surface plasmon resonance biosensor and a Magnetic Beads method. These three compounds were also confirmed in the serum in vivo, validated by binding affinity evaluation, molecular docking, and competitive enzyme-linked immunosorbent assay (ELISA) assay to act upon the interface of PD-1/PD-L1. Thus, these three ingredients could be potential PD-1/PD-L1 inhibitors and may serve as hit compounds for immunotherapeutic drug discovery. These results also highlight the efficiency of the dual-target surface plasmon resonance (SPR) and Magnetic Beads ligand fishing system in drug screening for disease treatment.

Keywords

Herbal extracts; Magnetic beads; PD-1/PD-L1 interactions; Screening; Surface plasmon resonance biosensor.

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