Evidence map›Paper›PMID 39235560›Full record

ArticleScience China. Life sciences2025

Blocking the PD-1 signal transduction by occupying the phosphorylated ITSM recognition site of SHP-2.

Wenjie Li, Wenyi Mei, Hewei Jiang, Jie Wang, Xiaoli Li, Lina Quan, Yanyan Diao, Yanni Ma, Sisi Fan, Zhuwei Xie and 20 more

Abstract read
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Article in Science China. Life sciences, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

9 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
  4. Strategies to target PD-1/PD-L1 in the tumor microenvironment.Cellular oncology (Dordrecht, Netherlands) · 2026
    Review
  5. Article
  6. Article
  7. Review
  8. Review
  9. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

30 authors.

Wenjie Li *Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science & Technology, Shanghai, 200237, China.
Wenyi Mei *Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science & Technology, Shanghai, 200237, China.
Hewei Jiang *Shanghai Center for Systems Biomedicine, Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Jiao Tong University, Shanghai, 200240, China.
Jie Wang *Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science & Technology, Shanghai, 200237, China.
Xiaoli Li *Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education, Yunnan Characteristic Plant Extraction Laboratory, Yunnan Provincial Center for Research & Development of Natural Products, State Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan, School of Pharmacy and School of Chemical Science and Technology, Yunnan University, Kunming, 650500, China.
Lina QuanShanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science & Technology, Shanghai, 200237, China.
Yanyan DiaoShanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science & Technology, Shanghai, 200237, China.
Yanni MaCAS Key Laboratory of Separation Sciences for Analytical Chemistry, National Chromatographic R & A Center, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, 116023, China.
Sisi FanShanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science & Technology, Shanghai, 200237, China.
Zhuwei XieShanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science & Technology, Shanghai, 200237, China.
Mengdie GongShanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science & Technology, Shanghai, 200237, China.
Huan ZhuShanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science & Technology, Shanghai, 200237, China.
Dewen BiKey Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education, Yunnan Characteristic Plant Extraction Laboratory, Yunnan Provincial Center for Research & Development of Natural Products, State Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan, School of Pharmacy and School of Chemical Science and Technology, Yunnan University, Kunming, 650500, China.
Feng ZhangDepartment of Cardiology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230027, China.
Lei MaShanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science & Technology, Shanghai, 200237, China.
Jian ZhangShanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science & Technology, Shanghai, 200237, China.
Yufeng GaoDepartment of Infectious Diseases, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, China.
Aris PaschalidisDepartment of Medicine, University of Massachusetts Chan Medical School, Worcester, MA, 01655, USA.
Honghuang LinDepartment of Medicine, University of Massachusetts Chan Medical School, Worcester, MA, 01655, USA.
Fangfang LiuDepartment of Pathophysiology, School of Basic Medical Sciences, Academy of Medical Science, College of Medicine, Zhengzhou University, Zhengzhou, 450001, China.
Kangdong LiuDepartment of Pathophysiology, School of Basic Medical Sciences, Academy of Medical Science, College of Medicine, Zhengzhou University, Zhengzhou, 450001, China.
Mingliang YeCAS Key Laboratory of Separation Sciences for Analytical Chemistry, National Chromatographic R & A Center, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, 116023, China.
Zhenjiang ZhaoShanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science & Technology, Shanghai, 200237, China.
Yajun DuanDepartment of Cardiology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230027, China.
Zhuo ChenShanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science & Technology, Shanghai, 200237, China.
Yufang XuShanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science & Technology, Shanghai, 200237, China.
Weilie XiaoKey Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education, Yunnan Characteristic Plant Extraction Laboratory, Yunnan Provincial Center for Research & Development of Natural Products, State Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan, School of Pharmacy and School of Chemical Science and Technology, Yunnan University, Kunming, 650500, China. xiaoweilie@ynu.edu.cn.
Shengce TaoShanghai Center for Systems Biomedicine, Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Jiao Tong University, Shanghai, 200240, China. taosc@sjtu.edu.cn.
Lili ZhuShanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science & Technology, Shanghai, 200237, China. zhulfl@ecust.edu.cn.
Honglin LiShanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science & Technology, Shanghai, 200237, China. hlli@ecust.edu.cn.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Targeting the PD-1/PD-L1 axis with small-molecular inhibitors is a promising approach for immunotherapy. Here, we identify a natural pentacyclic triterpenoid, Pygenic Acid A (PA), as a PD-1 signaling inhibitor. PA exerts anti-tumor activity in hPD-1 knock-in C57BL/6 mice and enhances effector functions of T cells to promote immune responses by disrupting the PD-1 signaling transduction. Furthermore, we identify SHP-2 as the direct molecular target of PA for inhibiting the PD-1 signaling transduction. Subsequently, mechanistic studies suggest that PA binds to a new druggable site in the phosphorylated PD-1 ITSM recognition site of SHP-2, inhibiting the recruitment of SHP-2 by PD-1. Taken together, our findings demonstrate that PA has a potential application in cancer immunotherapy and occupying the phosphorylated ITSM recognition site of SHP-2 may serve as an alternative strategy to develop PD-1 signaling inhibitors. In addition, our success in target recognition provides a paradigm of target identification and confirmation for natural products.

Indexed as

Mice, Inbred C57BLProgrammed Cell Death 1 ReceptorProtein Tyrosine Phosphatase, Non-Receptor Type 11Signal TransductionAnimalsCell Line, TumorHumansMicePhosphorylationPdcd1 protein, mouseProgrammed Cell Death 1 ReceptorProtein Tyrosine Phosphatase, Non-Receptor Type 11PTPN11 protein, humanimmunoreceptor tyrosine-based switch motifprogrammed death-1pygenic acid ASH2 domain-containing protein-tyrosine phosphatase-2site recognitiontarget identification

Identifiers

PMID39235560

What OpenQuestion holds

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.