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Published on: July 17, 2020
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
Summary
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.
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