Publication
Title
Selective inhibitors of fibroblast activation protein (FAP) with a (4-quinolinoyl)-glycyl-2-cyanopyrrolidine scaffold
Author
Abstract
Fibroblast activation protein (FAP) is a serine protease that is generally accepted to play an important role in tumor growth and other diseases involving tissue remodeling. Currently there are no FAP inhibitors with reported selectivity toward both the closely related dipeptidyl peptidases (DPPs) and prolyl oligopeptidase (PREP). We present the discovery of a new class of FAP inhibitors with a N-(4-quinolinoyl)-Gly-(2-cyanopyrrolidine) scaffold. We have explored the effects of substituting the quinoline ring and varying the position of its sp2 hybridized nitrogen atom. The most promising inhibitors combined low nanomolar FAP inhibition and high selectivity indices (>103) with respect to both the DPPs and PREP. Preliminary experiments on a representative inhibitor demonstrate that plasma stability, kinetic solubility, and log D of this class of compounds can be expected to be satisfactory.
Language
English
Source (journal)
ACS medicinal chemistry letters. - -
Publication
2013
ISSN
1948-5875
DOI
10.1021/ML300410D
Volume/pages
4 :5 (2013) , p. 491-496
ISI
000318892800016
Full text (Publisher's DOI)
Full text (publisher's version - intranet only)
UAntwerpen
Faculty/Department
Research group
Project info
Development of potent and selective inhibitors of fibroblast activation protein, a new target in the treatment of malignant diseases.
Research on bacterial virulence inhibitors with predictive in vitro and in vivo models.
Dipeptidyl peptidases beyond glucose homeostasis: from biochemistry to physiological importance.
Activity-based probes for PET imaging of protease activity.
Publication type
Subject
Affiliation
Publications with a UAntwerp address
External links
Web of Science
Record
Identifier
Creation 12.04.2013
Last edited 09.10.2023
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