Molecular recognition of fibroblast activation protein for diagnostic and therapeutic applications
Language English Country Netherlands Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't, Review
PubMed
32171757
DOI
10.1016/j.bbapap.2020.140409
PII: S1570-9639(20)30054-6
Knihovny.cz E-resources
- Keywords
- Activity-based probes, Cancer tissue targeting, FAP inhibitors, FAP substrates, Fibroblast activation protein,
- MeSH
- Dipeptidyl Peptidase 4 metabolism MeSH
- Endopeptidases MeSH
- Fibroblasts metabolism MeSH
- Catalytic Domain MeSH
- Humans MeSH
- Membrane Proteins chemistry drug effects metabolism MeSH
- Molecular Structure MeSH
- Tumor Microenvironment MeSH
- Neoplasms diagnosis metabolism therapy MeSH
- Prodrugs MeSH
- Prolyl Oligopeptidases MeSH
- Serine Endopeptidases chemistry drug effects metabolism MeSH
- Substrate Specificity MeSH
- Gelatinases chemistry drug effects metabolism MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Review MeSH
- Names of Substances
- Dipeptidyl Peptidase 4 MeSH
- DPP4 protein, human MeSH Browser
- Endopeptidases MeSH
- fibroblast activation protein alpha MeSH Browser
- Membrane Proteins MeSH
- Prodrugs MeSH
- PREPL protein, human MeSH Browser
- Prolyl Oligopeptidases MeSH
- Serine Endopeptidases MeSH
- Gelatinases MeSH
Fibroblast activation protein (FAP) is a non-classical serine protease expressed predominantly in conditions accompanied by tissue remodeling, particularly cancer. Due to its plasma membrane localization, FAP represents a promising molecular target for tumor imaging and treatment. The unique enzymatic activity of FAP facilitates development of diagnostic and therapeutic tools based on molecular recognition of FAP by substrates and small-molecule inhibitors, in addition to conventional antibody-based strategies. In this review, we provide background on the pathophysiological role of FAP and discuss its potential for diagnostic and therapeutic applications. Furthermore, we present a detailed analysis of the structural patterns crucial for substrate and inhibitor recognition by the FAP active site and determinants of selectivity over the related proteases dipeptidyl peptidase IV and prolyl endopeptidase. We also review published data on targeting of the tumor microenvironment with FAP antibodies, FAP-targeted prodrugs, activity-based probes and small-molecule inhibitors. We describe use of a recently developed, selective FAP inhibitor with low-nanomolar potency in inhibitor-based targeting strategies including synthetic antibody mimetics based on hydrophilic polymers and inhibitor conjugates for PET imaging. In conclusion, recent advances in understanding of the molecular structure and function of FAP have significantly contributed to the development of several tools with potential for translation into clinical practice.
References provided by Crossref.org
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