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Published on: January 22, 2019
Pin1 inhibitors: Pitfalls, progress and cellular pharmacology
Jonathan D Moore1, Andrew Potter
1Horizon Discovery, Cambridge Research Park, Cambridge CB25 9TL, UK. j.moore@horizondiscovery.com
Bioorganic & Medicinal Chemistry Letters
|June 26, 2013
Summary
Pin1 inhibitors show promise for cancer therapy, as Pin1 deficient mice resist cancer development. However, effective chemical biology tools and improved Pin1 inhibitors are still needed for cancer treatment.
Area of Science:
- Oncology
- Molecular Biology
- Drug Discovery
Background:
- Pin1 (Peptidyl-prolyl cis-trans isomerase) is implicated in cancer development.
- Pin1 deficiency in mice confers resistance to MMTV-driven Ras or Erb2-induced breast cancers.
Purpose of the Study:
- To critically evaluate the potential of Pin1 inhibitors in cancer therapy.
- To discuss the challenges and progress in identifying Pin1 antagonists.
- To assess the suitability of current compounds as chemical biology tools for Pin1 research.
Main Methods:
- Review of structure-based drug design efforts for Pin1 inhibitors.
- Analysis of peptidic inhibitors and natural products like epigallocatechin gallate (EGCG).
- Critical discussion of the modes of action and specificity of identified Pin1 antagonists.
Main Results:
- Pin1 inhibitors present a compelling hypothesis for cancer therapy.
- Structure-based drug design has yielded potent Pin1 antagonists.
- Natural products, including EGCG, have been identified as Pin1 blockers.
Conclusions:
- A suitable chemical biology tool for probing Pin1 function is currently lacking.
- Further research is needed for Pin1 target validation.
- Prospects for identifying improved Pin1 inhibitors remain open.
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