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Pin1 in cancer: Signaling mechanisms, structural basis and advances in inhibitor development

Wu Wu1, Jiao Mo1, Jianzhou Su2

  • 1Department of Plastic and Burn Surgery, West China Hospital of Sichuan University, Chengdu, 610041, China.

European Journal of Medicinal Chemistry
|July 21, 2026
PubMed

Insights

Pin1, a key enzyme in cell signaling, regulates protein function and is implicated in cancer. This review explores strategies for developing Pin1 inhibitors, addressing challenges in drug development.

Area of Science:

  • Biochemistry and Molecular Biology
  • Enzymology
  • Cancer Biology

Background:

  • Pin1 (Peptidyl-prolyl cis-trans isomerase) catalyzes cis-trans isomerization of phosphorylated Ser/Thr-Pro motifs, regulating protein function.
  • Pin1 integrates kinase signaling with crucial cellular processes like transcription, cell-cycle progression, and apoptosis.
  • Dysregulation of Pin1 is common in cancer, promoting oncogenic signaling and malignant progression, making it a therapeutic target.

Purpose of the Study:

  • To review current strategies targeting Pin1 for therapeutic intervention.
  • To analyze the mechanisms of various Pin1 inhibitors (noncovalent, covalent, degradation-based).
  • To discuss the translational limitations and challenges in developing Pin1-targeting drugs.

Main Methods:

  • Literature review of current Pin1-targeting strategies.
  • Analysis of inhibitor mechanisms, including noncovalent, covalent, and degradation-based approaches.
  • Evaluation of translational challenges and limitations in drug development.

Main Results:

  • Pin1's unique substrate recognition and broad biological roles present significant challenges for drug development.
  • Various strategies, including small molecule inhibitors and degradation-based approaches, are being explored to target Pin1.
  • Understanding Pin1's conformation-driven substrate recognition is crucial for effective inhibitor design.

Conclusions:

  • Pin1 is a promising therapeutic target in cancer due to its role in oncogenic signaling.
  • Developing effective Pin1 inhibitors requires overcoming challenges related to substrate recognition and biological complexity.
  • Future drug design should focus on innovative strategies to effectively target Pin1 and its associated pathways.
Keywords:
Drug designPeptidyl-prolyl cis/trans isomerasePin1Targeted therapy

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